Clinicopathological Characteristics Of Patients Research Articles

Associations of BRAFV600E mutation with the American College of Radiology Thyroid Imaging Reporting and Data System and clinicopathological characteristics in pediatric patients with papillary thyroid carcinoma.

Identifying the associations between BRAFV600E mutation, the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) and clinicopathological characteristics could assist in making appropriate treatment strategies for pediatric patients with papillary thyroid carcinoma. To retrospectively assess the associations between BRAFV600E mutation, TI-RADS, and clinicopathological characteristics in pediatric patients with papillary thyroid carcinoma. Between May 2013 and May 2023, pediatric patients with papillary thyroid carcinoma who underwent thyroidectomy were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to determine the associations between BRAFV600E mutation, TI-RADS, and clinicopathological characteristics. The diagnostic performance of TI-RADS to predict BRAFV600E mutation was assessed. The BRAFV600E mutation was found in 59.1% (39/66) of pediatric patients with papillary thyroid carcinoma. Multivariate analyses showed that hypoechoic/very hypoechoic [odds ratio (OR) = 8.48; 95% confidence interval (CI) = 1.48-48.74); P-value = 0.02] and punctate echogenic foci (OR = 24.3; 95% CI = 3.80-155.84; P-value = 0.001) were independent factors associated with BRAFV600E mutation. In addition, BRAFV600E mutation was significantly associated with TI-RADS 5 (OR = 12.61; 95% CI = 1.28-124.49; P-value = 0.03). There were no associations between BRAFV600E mutation and nodule size, composition, shape, margin, cervical lymph node metastasis, or Hashimoto's thyroiditis (P-value > 0.05). Combined with hypoechoic/very hypoechoic and punctate echogenic foci, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 89.7%, 85.2%, 89.7%, 85.2%, and 87.9%, respectively. Hypoechoic/very hypoechoic, punctate echogenic foci, and TI-RADS 5 are independently associated with BRAFV600E mutation in pediatric patients with papillary thyroid carcinoma.

Clinicopathological Features of Elderly Patients with Colonic Volvulus

Objective: Sigmoid volvulus is most commonly seen in patients between 60 and 80 years old. The management of volvulus depends on its location and clinical presentation. The fundamental aspects of treatment include evaluating the viability of the colon, relieving the obstruction, and preventing the possibility of recurrence. We aimed to present the clinicopathological characteristics of geriatric colonic volvulus patients treated in a single center. Methods: Patients diagnosed with colonic volvulus and treated in this hospital were included in the study. Mortality rates of patients who underwent and did not undergo preoperative colonoscopic detorsion were compared statistically. In addition, diseases that affect the quality of life and cause deterioration in bowel movements and habits were determined, and these diseases' effect on mortality was evaluated. Results: Forty-four patients who underwent emergency surgery due to volvulus were included in our study. There was sigmoid colon perforation in two patients and cecum perforation in 1 patient. Two patients had cecal volvulus, and right hemicolectomy was performed in these patients; anastomosis was performed in one, and ileostomy was performed in the other. Sigmoid resection was performed in 36 patients, subtotal colectomy in 5 patients, right hemicolectomy in 2 patients, and sigmoidopexy with laparotomy and reduction in 1 patient. Thirteen patients (29.5%) underwent preoperative colonoscopy, and in eight cases, the procedure was conducted a day before the surgery, with the operation being carried out semi-urgently the next day. Conclusion: Intestinal volvulus is a rare condition that can occur in any part of the large intestine. However, it is a severe medical issue that requires prompt diagnosis and treatment due to the possibility of intestinal damage and mortality.

Abstract PO1-05-12: Pooled clinical trial data analyses comparing the biology of HER2-low vs HER2-0 breast cancer in patients with metastatic breast cancer following treatment with standard single agent chemotherapy

Abstract Background: Prior analyses of observational data suggest that for patients with metastatic breast cancer (MBC), tumor biology does not vary by HER2-low vs. HER2-0 expression given similar overall survival (OS) times after accounting for patients’ clinicopathologic features including hormone receptor (HR) status. We sought to evaluate potential differential biology by HER2-low status by (1) studying data pertaining to patients treated in historic clinical trials (i.e., data collected to measure associations between protocol defined treatments and outcomes) and (2) evaluating the endpoint of progression-free survival (PFS) in addition to OS following treatment with standard single agent chemotherapy for MBC. Methods: Pooling anonymized clinical trial data from studies within the Medidata Enterprise Data Store, we identified 142 women with HER2-negative MBC who received treatment with an NCCN recommended single agent chemotherapy in the context of a clinical trial. Using patient-level immunohistochemistry (IHC) results, we categorized patients as either HER2-low (IHC 1+/2+ and not amplified by in situ hybridization) or HER2-0 (IHC 0). We compared patients’ baseline demographic and clinicopathologic features according to HER2-low vs HER2-0 status. We used Cox proportional-hazard models stratified by HR status to estimate OS and PFS according to HER2-low vs HER2-0 classification while adjusting for patients' baseline demographic and clinicopathologic attributes. Results: Patients with HER2-low disease represented 20% (28/142) of the HER2-negative cohort. Twenty-five percent (7/28) of HER2-low patients had tumors that expressed hormone receptors compared with 17% (19/114) of HER2-0 patients (p=0.31). In this cohort, the maximum follow up time was 38.4 months. For HER2-low patients vs HER2-0 patients, the median OS was 10.7 vs. 12.7 months (p=0.37), and the median PFS was 3.5 vs. 2.9 months (log rank test, p=0.53) respectively. In Cox proportional-hazard models that adjusted for patient demographic and clinicopathologic features and were stratified by HR status, patients with HER2-low tumors had an 16% elevated (non-significant) hazard of death compared with patients with HER2-0 tumors (HR 1.16, 95% CI: 0.69-1.95) and a 22% reduced (non-significant) hazard of progression or death (HR 0.78, 95% CI: 0.45-1.35). Conclusions: Analyses of pooled historic clinical trial data pertaining to women with HER2-negative MBC who were treated with single agent chemotherapy revealed no meaningful clinical differences in either OS or PFS endpoints according to HER2-negative subtypes (i.e., HER2-low vs. HER2-0) after accounting for patient demographic and clinicopathologic features. These results support prior findings from observational research suggesting that there are no biological differences associated with HER2-negative subtypes. Table. Multivariable Cox Proportional Hazards Models for OS and PFS Stratified by Hormone Receptor Status, (N=134) Variable OS PFS HR* 95% CI HR* 95% CI Age (decade) 0.84 0.70-1.01 0.86 0.72-1.01 Race White 1.00 (referent) 1.00 (referent) Black 1.75 0.84-3.63 1.57 0.66-3.73 Asian 0.93 0.47-1.80 1.33 0.71-2.51 Other 1.69 0.45-6.38 2.10 0.62-7.15 Ethnicity Non-Hispanic or Latino 1.00 (referent) 1.00 (referent) Hispanic or Latino 2.10 0.95-4.64 1.02 0.44-2.35 HER2 Characterization HER2-0 1.00 (referent) 1.00 (referent) HER2-1+/2+ 1.16 0.69-1.95 0.78 0.45-1.35 Prior Lines of Chemotherapy for Metastatic Disease 0 1.00 (referent) 1.00 (referent) 1 0.82 0.46-1.46 1.13 0.65-1.95 2 0.69 0.35-1.36 1.00 0.52-1.93 3 0.59 0.10-3.42 2.18 0.45-10.50 ECOG Performance Status 0 1.00 (referent) 1.00 (referent) 1 1.65 1.07-2.54 1.57 1.02-2.43 Legend: OS=overall survival; PFS=progression-free survival; HR=hazard ratio; HER2=human epidermal group factor receptor 2; ECOG=Eastern Cooperative Oncology Group. *Analyses adjusted for clinical trial membership (coefficients not reported) Citation Format: Elizabeth Lamont, Emily Stein, Paolo Tarantino, Sara Tolaney, Corinne Ahlberg, Krishna Chinnathambu, Jiezhi Qi, Kala Tummagunta, Jackie Bilan, Ruthanna Davi, Lisa Ensign. Pooled clinical trial data analyses comparing the biology of HER2-low vs HER2-0 breast cancer in patients with metastatic breast cancer following treatment with standard single agent chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-12.

Abstract PO1-28-03: Impact of the Oncotype DX® test over time and association with clinicopathological characteristics of Peruvian patients with early breast cancer: Experience in the last 15 years

Abstract Introduction: Gene expression assays provide prognostic and therapy-predictive information that complements management of early breast cancer patients. Oncotype DX® had showed prognostic and prediction of adjuvant chemotherapy benefit. The present study evaluates the impact of Oncotype DX® on therapeutic decision-making for 15 years and explores the association of clinicopathological characteristics with the Recurrence Score (RS) in Peruvian patients with early breast cancer. Material and methods: A retrospective multicenter analysis of 759 breast cancer patients treated in three oncological centers in Lima-Peru (Instituto Nacional de Enfermedades Neoplásicas, Oncosalud and Ricardo Palma) between 2007 and 2022 was conducted. Risk groups were classified according to Oncotype DX® result and menopausal status. For premenopausal women ≤ 50 years: low (RS=0-20), intermediate (RS=21-25) and high-risk (RS=26-100). A descriptive analysis was evaluated to observe the trend and profile of the patients who used the Oncotype test in 5 time periods (2007-2009, 2010-2013, 2014-2016, 2017-2019, 2020-2022). Subsequently, chi-square, t-test, analysis of variance and Poisson linear regression tests were applied to compare clinicopathological features with RS. Finally, univariate and multivariate analyses were performed using Cox logistic regression to identify the probability of association with the high-risk group. Results: 642 patients were included, 78.5% were postmenopausal, and 64.2% had clinical stage (CS) I. Overall, 63.4% had no recommendation for chemotherapy and only 5.6% had recurrence. 74.8% were classified as low-risk according to the Oncotype DX® result. Postmenopausal patients had negative lymph nodes (95.4%), the majority had undergone conservative surgery (71.8%) and had a low rate of breast reconstruction (11.9%). An increase in the use of Oncotype DX® was observed over time, especially in premenopausal patients (from 4.5% in 2007 to 36.9% in 2022). A significant association was found between luminal B subtype (p < 0.0001), histological grade 3 (p < 0.0001) and T3 vs. T1/2 (p=0.025). In univariate analysis, luminal B subtype (vs. luminal A, OR=5.56, 95% CI, 2.80-12.3, p< 0.001), T3 (vs. T1/2, OR=2.84, 95% CI, 0.13-30.0, p=0.006), histological grade 3 (vs. 1/2, OR=13.1, 95% CI, 5.35-39.6, p< 0.001) and histology (other vs. ductal/lobulillar/mucinous, OR=2.94, 95% CI, 0.57-13.5, p=0.003) provided a higher probability of obtaining a high-risk RS result. Similar results were found in multivariate analysis. Conclusion: The use of the Oncotype DX® had a significant impact on therapeutic decision-making in Peruvian patients with early breast cancer, with an increase of use in the last 15 years. A high-risk RS was associated with luminal B subtype, histological grade 3 and T3 tumor size, which could facilitate risk stratification and provide valuable information for the need of adjuvant chemotherapy. Keywords: Early breast cancer, Oncotype DX®, clinicopathological characteristics, Recurrence Score (RS), Peru Oncotype PERU Table Citation Format: Steffi Katheryne Gonzalez Bocanegra, Guillermo valencia Mesías, Yomali Aroa Ferreyra Chombo, Karoll Tatiana Meza Garcia, Mariano Lopez-Pereyra, Jorge Torres Maldonado, Edgar Fermín Yan Quiroz, Zaida Morante Cruz, Jose Cotrina-Concha, Henry Gómez, Gabriela Calderon Valencia, Mauricio León Rivera. Impact of the Oncotype DX® test over time and association with clinicopathological characteristics of Peruvian patients with early breast cancer: Experience in the last 15 years [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-28-03.

Abstract PO2-14-03: Novel Metrics of HER2 Heterogeneity in HER2-Positive and HER2-Low Breast Cancer via High Dimensional Multiplexed Immunofluorescence Spatial Profiling

Abstract Background: Categorizing breast cancer HER2/ERBB2 expression as “positive” or “negative” is no longer sufficient, with evidence that treatment response and outcomes are associated with HER2 “low” status and HER2 intratumoral heterogeneity. We hypothesized that interrogating HER2 heterogeneity (HER2het) across multiple spatial resolutions would more accurately capture HER2 diversity and be associated with clinical outcomes. Methods: We interrogated tumor cell and microenvironmental features by profiling 1,113,204 single cells in tissue sections from 171 HER2+/HER2low cancers via custom 25-marker high dimensional multiplexed immunofluorescence (HDmIF) using NeoGenomics MultiOmyx, with adjacent section HER2 immunohistochemistry (IHC). We developed novel metrics to concurrently: 1) interrogate HER2 heterogeneity at four spatial resolutions; 2) use machine learning to translate HER2 IF to IHC, termed ‘HAIQu’ (HER2 Automated Immunofluorescence Quantification), scoring HER2 IF expression according to ASCO/CAP guidelines; 3) delineate HER2 signaling phenotypes at the tumor cell level based on six HER2-related proteins; 4) evaluate immunophenotype of 23 immune cell types. We evaluated the association of these novel HER2het metrics with patient clinicopathologic features, recurrence-free survival (RFS), overall survival (OS), and diverse antibody markers representing tumor cell intrinsic processes and tumor-immune microenvironment (TME). Results: 1166 regions of interest were analyzed from 208 unique tumors profiled. Median follow-up from diagnosis was 143 months and 98.9% (n=183/185) received HER2-directed therapy in the (neo)adjuvant or metastatic setting. Our HAIQu scoring system effectively translated adjacent section HER2 IF to IHC with 97.9% concordance between HAIQu and clinical IHC scoring. Single-cell phenotypic analyses of 392,984 HER2+/PanCK+ tumor cells’ concurrent expression of six HER2-positive breast cancer related proteins (HER2, HER3, EGFR, pAKT, ER, KI67) using an unsupervised neural network-based self-organizing map approach resulted in 7 HER2 signaling cell phenotypes. Most patient samples are dominated by a single cell cluster but, intriguingly, Cluster 1 cells (EGFR-low) predominate in tumors with high HER2 cell membrane heterogeneity (ANOVA p=0.003). Evaluation of immunophenotype in hormone receptor-negative, HER2+ tumors, demonstrated significant association with immune cluster and recurrence-free survival (RFS; log-rank p=0.024) with zero RFS events among immune-high versus median survival of only 53.5mo among immune low-PDL1 low tumors. A multivariable Cox proportional hazards model including single cell HER2-heterogeneity (only significant metric on univariate), receptor subtype, and immunophenotype cluster demonstrated significant association with RFS (overall model log-rank p=0.005) and each significantly contributed to the model (all p< 0.05). Conclusions: We present novel metrics of HER2 heterogeneity via HDmIF, which offer detailed characterization of the diversity of HER2 expression in a large, clinically-annotated cohort with long-term follow-up. Identification of a strong association between immunophenotype and RFS supports further investigation of the highly immune activated subsets of ER-/HER2+ breast cancer. Strong correspondence of HER2 IF and IHC and our HAIQu methodology offers a pathway to translation of HER2het metrics to clinical practice. Table 1. Association of HER2 Heterogeneity Metrics with Recurrence-Free Survival Citation Format: David Tallman, Anna Juncker-Jensen, Harry Nunns, Kevin Gallagher, Heather LeFebvre, Karen Yamamoto, Katharine Collier, Mark Vater, Ava Strahan, Mathew Cherian, Ashley Pariser, Preeti Sudheendra, Bhuvaneswari Ramaswamy, Margaret Gatti-Mays, Ainura Kyshtoobayeva, Zaibo Li, Daniel Stover, Kai Johnson. Novel Metrics of HER2 Heterogeneity in HER2-Positive and HER2-Low Breast Cancer via High Dimensional Multiplexed Immunofluorescence Spatial Profiling [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-14-03.

Abstract PO5-02-12: Comparison of survival outcomes according to axillary ultrasonography findings and cytology results in early-stage breast cancer patients

Abstract Purpose: Axillary lymph node dissection and sentinel lymph node biopsy are associated with increased risk of post-surgical complications including lymphedema and recent trials have raised questions about the therapeutic benefit of axillary operation in early-stage breast cancer patients. While treatment options for lymph nodes with negative findings on axillary ultrasonography (AUS) or positive findings on fine needle aspiration biopsy (FNAB) are evident, data regarding lymph nodes that are suspicious on AUS but negative by FNAB are limited. Thus, we aimed to compare clinicopathological characteristics of AUS positive and FNAB negative patients with those of AUS negative or FNAB positive patients. Materials and Methods: Medical records of patients who underwent breast cancer surgery between January 2010 and December 2017 were reviewed. Patients were grouped into the following three groups: (a) negative findings on AUS, (b) suspicious findings on AUS but negative on FNAB, (c) and FNAB positive. A total of 4,506 patients were included for analysis, with 3,771 patients with no suspicious lymph nodes on AUS, 557 patients who had suspicious AUS findings but were negative on FNAB, and 178 patients with positive findings on both AUS and FNAB. Primary endpoints were disease free survival (DFS) and recurrence free survival (RFS), and secondary endpoint was overall survival (OS). Results: At a median follow-up period of 92 months, DFS and RFS was significantly higher in the AUS negative group compared to the other two groups (10-year-DFS: 91.6% vs 87.5% vs 75.7%, 10-year-RFS: 95.0% vs 89.9% vs 77.1%, p < 0.001). In terms of OS, AUS negative group and the AUS positive and FNAB negative group did not show statistically significant survival difference (10-year-OS: 94.5% vs 92.8%, p = 0.061), while the FNAB positive group showed significantly lower survival rates (10-year-OS: 81.8%, p < 0.001). Multivariable analysis revealed that not AUS positive and FANB negative but positive FNAB was significantly associated with poor RFS. Moreover, hormone receptor (HR) positive and HER2 negative subtype showed poor DFS and RFS in subgroup analysis. Conclusion: Early breast cancer patients with suspicious findings on AUS but negative FNAB results had similar OS but inferior DFS and RFS compared to those with negative features on AUS, especially in HR(+)HER2(-) subtype. While further prospective trials are warranted to determine whether additional treatment is necessary, close surveillance is recommended for this subgroup of patients. Figure1. Overall survial and Disease free survival according to axillay US and FNAB status Table1. patients' characteristics Table2. prognostic factors for overall survival and disease free survival related to axillary US and FNAB status Citation Format: Suk Jun Lee. Comparison of survival outcomes according to axillary ultrasonography findings and cytology results in early-stage breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-12.

Bioinformatics analysis and validation of HAUS6 as a key prognostic gene in squamous cell carcinoma of the tongue

ObjectiveTo explore the expression of HAUS6 in squamous cell carcinoma of the tongue (TSCC) and its relationship with the clinicopathological features of patients, and to further provide new ideas and therapeutic targets for curing TSCC.DesignThe Cancer Genome Atlas (TCGA) database was used to screen for differentially expressed genes (DEGs) between TSCC and normal tissues and survival analysis. DEGs of HAUS6 were screened and analyzed for GO, KEGG and GSEA enrichment. Exploring the correlation of HAUS6 with immune cell infiltration and immune checkpoint-related genes. The expression of HAUS6 in tumor and paraneoplastic tissues was confirmed by immunohistochemistry and Western Blot. ResultsAnalysis of the TCGA database results showed that expression of HAUS6 mRNA was significantly enhanced and correlated with overall survival (OS, p<0.05) in TSCC. HAUS6 expression correlated with the level of immune cell infiltration and immune checkpoint-related genes. Immunohistochemistry and Western Blot confirmed that the expression level of HAUS6 protein was significantly higher in tumor tissues than in paraneoplastic tissues, and that tumor size and hypo-differentiation were higher in the HAUS6 high expression group than in the low expression group in TSCC (p<0.05). ConclusionsIn conclusion, these analyses suggest that HAUS6 can act as an independent predictor of prognosis (p<0.05) and high HAUS6 expression is strongly associated with poor prognosis.

Clinicopathological features, prognostic factor analysis, and survival nomogram of patients with double primary cancers involving lung cancer.

Although the incidence of double primary cancers (DPCs) involving lung cancer is rising, they have not been studied sufficiently. This study retrospectively analyzed the clinicopathological and prognostic characteristics of DPC patients with lung cancer and developed a survival nomogram to predict the individual OS rates. We included 103 DPC patients with lung cancer from Shengjing Hospital between 2016 and 2021. Based on the 6-month cancer occurrence interval, the cases were categorized as synchronous DPCs (sDPCs) or metachronous DPCs (mDPCs). Furthermore, the mDPCs were subdivided based on whether the lung cancer occurred first (LCF cohort) or the other cancer occurred first (OCF cohort). Among the patients, 35 (33.98%) and 68 (66.02%) had sDPCs and mDPCs, respectively. In the mDPCs cohort, 18 (26.47%) belonged to the LCF cohort and 50 (73.53%) to the OCF cohort. The most frequent primary cancer sites were the breast (27.18%), colorectum (22.33%), and urinary system (18.45%). Independent risk factors for progression-free survival were Stage IV lung cancer (p = 0.008) and failure to undergo radical lung cancer surgery (p = 0.028). The risk factors for OS included squamous carcinoma (p = 0.048), Stage IV lung cancer (p = 0.001), single cancer resection plus drug therapy (p < 0.001), drug therapy alone (p = 0.002), failure to undergo radical lung cancer surgery (p = 0.014), and chemotherapy (p = 0.042). The median OS was 37 months, with 3- and 5-year rates of 50.9% and 35.9%, respectively. DPCs involving lung cancer account for 1.11% of cases. The breast, colorectum, and urinary system were the most common extra-pulmonary sites, and mDPCs were more frequent than sDPCs. Radical lung cancer surgery significantly affects prognosis, and drug therapy alone may be preferable when only one tumor is operable. The developed nomogram can accurately predict individual 3-year and 5-year OS rates.

Sub-lobar resection versus lobectomy for challenging intraoperative frozen sections in lung adenocarcinoma within 3 cm

ObjectivesIntraoperative frozen section (FS) analysis is pivotal in guiding surgical interventions for early-stage lung adenocarcinoma. However, the challenge arises when distinguishing between Minimally Invasive Adenocarcinoma (MIA) and Invasive Adenocarcinoma (IAC) poses diagnostic difficulties. This study investigates the prognosis and clinicopathological characteristics of patients encountering this diagnostic challenge. MethodsWe conducted a retrospective analysis of 7,082 intraoperative FSs from early-stage lung adenocarcinoma cases. The cases with pulmonary nodules within 3cm and diagnosed as indeterminate FSs were included. We analyzed baseline data, computed tomography (CT) findings, and pathological characteristics. Prognostic data were obtained from patients with confirmed IAC diagnoses through final pathological examination. ResultsOut of 7,082 FSs, 551 cases presented challenges in distinguishing between MIA and IAC. Upon final pathological examination, 233 cases were identified as IAC, while 314 were classified as MIA. The median invasive pathological size in the IAC group was larger than that in the MIA group (0.6cm vs 0.3cm). 131 cases (56.2%) with IAC underwent lobectomy, while 102 cases (43.8%) underwent sub-lobar resection.Among the MIA cases, 220 cases (69.8%) underwent sub-lobar resection, while 95 cases (30.2%) underwent lobectomy. No recurrence and disease specific death was observed during the follow-up period, regardless of surgical strategy. ConclusionsIndeterminate intraoperative FSs, posing diagnostic challenges in distinguishing between MIA and IAC. Sub-lobar resection presented the same long term survival benefit compared with the lobectomy for indeterminate lung adenocarcinoma within 3cm during intraoperative FSs.

Expression of B7-H4 in endometrial cancer and its impact on patients' prognosis.

The aim of the study was to evaluate the B7-H4 expression in endometrial cancer cells and to investigate its relationship with patient prognosis and clinicopathological features of the disease. We performed a single-center, retrospective cohort study that included endometrial cancer patients treated between 2012 and 2019. B7-H4 expression in specimens obtained from 63 patients was examined by immunohistochemical staining. The evaluation of B7H4 immunoreactivity was assessed using Immunoreactivity Scoring (IRS) system. B7-H4 reactivity was observed in all, except one, endometrial cancer patients (98%). Staining intensity: no reaction in one case, weak in 16 (24%) patients, moderate in 25 (37%), and strong in 22 (35%). Twenty-nine (46%) patients showed B7-H4 immunoreactivity in more than 60% of cells, while, in 18 (29%) cases and 16 (25%) patients, the percentages were 30-60% and < 30% respectively. Median IRS was 2 (range 0-6). We found a significantly worse overall survival (OS) rate for patients with high versus low B7-H4 IRS (p = 0.03), however, in multivariate analysis, the difference in patient survival was close to the significance level (p = 0.052). B7-H4 expression was not related to histopathological type of the tumor, tumor grade, lymph node metastases, or the FIGO stage of the disease. Our result suggests that B7-H4 expression might be a useful prognostic factor in endometrial cancer.

Association of the TRIM family protein with survival outcomes and clinicopathological features in colorectal cancer: a systematic review and meta-analysis

BackgroundThe tripartite motif (TRIM) proteins have been reported to play crucial roles in various malignancies. However, the clinical significance of TRIM proteins in colorectal cancer (CRC) remains controversial. This study aimed to evaluate the association between TRIM proteins and the clinicopathological features and survival outcomes in patients with CRC.MethodsWe performed a meta-analysis to investigate whether TRIM is a prognostic factor in CRC. PubMed, Embase, Web of Science, CNKI and Weipu databases were searched to identify eligible studies that evaluated the association between TRIM proteins and overall survival (OS), as well as the clinicopathological features of patients with CRC. Hazard ratios (HR) or odds ratios (OR) with 95% confidence interval (CI) were derived and pooled using a fixed-effects model.ResultsFrom inception to March 2023, we extracted study characteristics and prognostic data for each identified study. Twelve studies enrolling 1608 patients were eligible for inclusion. Data on OS and recurrence-free survival (RFS) were available for 12 and 2 studies, respectively. The pooled analysis results showed a significant correlation between the elevated TRIM proteins and shorter OS (HR = 2.42, 95% CI: 1.96–2.99) and worse RFS (HR = 2.51, 95% CI: 1.78–3.54) in patients with CRC. The combined ORs indicated that TRIM protein over-expression was significantly associated with advanced TNM stage (OR = 2.26, 95% CI: 1.25–4.10), deep tumor invasion (OR = 2.01, 95% CI: 1.04–3.88), lymph node metastasis (OR = 2.99, 95% CI: 2.19–4.09) and perineural invasion (OR = 1.95, 95% CI: 1.18–3.23).ConclusionsOur findings suggest that TRIM proteins can predict tumor progression and poor prognosis in CRC. Therefore, TRIM proteins may be promising therapeutic targets for patients with CRC.Graphical

The immune response-related genomic alterations in patients with malignant melanoma.

Immune checkpoint inhibitors (ICIs) significantly improve the survival outcomes of patients with advanced melanoma. However, response varies among from patient to patient and predictive biomarkers are urgently needed. We integrated mutational profiles from next-generation sequencing (NGS) data and clinicopathologic characteristics of melanoma patients to investigate whether tumor genomic profiling contribute to clinical benefit of ICIs treatment. The majority of genes identified with high mutation frequency have all been reported as well-known immunotherapy-related genes. Thirty-five patients (43.2%) had at least 1 BRAF/RAS/NF1 mutation. The other 46 (56.8%) melanomas without BRAF/RAS/NF1 mutation were classified as Triple-WT. We identified mutational signature 6 (known as associated with defective DNA mismatch repair) among cases in this cohort. Compared to patients with PD-L1 expression (TPS < 1%), patients with PD-L1 expression (TPS ≥ 1%) had significantly higher median progression-free survival (mPFS), but no significantly higher durable clinical benefit (DCB) rate. In contrast, FAT1, ATM, BRCA2, LRP1B, and PBRM1 mutations only occurred frequently in patients with DCB, irrespective of PD-L1 expression status. Our study explored molecular signatures of melanoma patients who respond to ICIs treatment and identified a series of mutated genes that might serve as predictive biomarker for ICIs responses in melanoma.

Clinicopathologic and endoscopic characteristics of ten patients with gastric hamartomatous inverted polyp: a single center case series

BackgroundGastric hamartomatous inverted polyps (GHIPs) are not well characterized and remain diagnostically challenging due to rarity. Therefore, this study aims to investigate the clinicopathologic and endoscopic characteristics of patients with GHIP.MethodsWe retrospectively reviewed clinicopathologic and endoscopic features of ten patients with GHIP who were admitted to Beijing Friendship Hospital from March 2013 to July 2022. All patients were treated successfully by endoscopic resection.ResultsGHIPs were usually asymptomatic and found incidentally during gastroscopic examination. They may be sessile or pedunculated, with diffuse or local surface redness or erosion. On endoscopic ultrasonography, the sessile submucosal tumor-type GHIP demonstrated a heterogeneous lesion with cystic areas in the third layer of the gastric wall. Histologically, GHIPs were characterized by a submucosal inverted proliferation of cystically dilated hyperplastic gastric glands accompanied by a branching proliferation of smooth muscle bundles. Inflammatory cells infiltration was observed in the stroma, whereas only one patient was complicated with glandular low-grade dysplasia. Assessment of the surrounding mucosa demonstrated that six patients (60%) had atrophic gastritis or Helicobacter pylori–associated gastritis, and four patients (40%) had non-specific gastritis. Endoscopic resection was safe and effective.ConclusionsGHIPs often arise from the background of abnormal mucosa, such as atrophic or H.pylori-associated gastritis. We make the hypothesis that acquired inflammation might lead to the development of GHIPs. We recommend to make a full assessment of the background mucosa and H. pylori infection status for evaluation of underlying gastric mucosal abnormalities, which may be the preneoplastic condition of the stomach.

Sex disparity in clinical characteristics and long-term prognosis after liver resection for patients with intrahepatic cholangiocarcinoma: A propensity score matching analysis

AimTo compare the survival outcomes between male and female patients with intrahepatic cholangiocarcinoma who underwent liver resection. MethodsData from 976 consecutive intrahepatic cholangiocarcinoma patients undergoing liver resection between January 2005 and May 2013 at the Eastern Hepatobiliary Surgery Hospital were prospectively collected and retrospectively reviewed. Patient clinicopathological characteristics, overall survival, and cumulative recurrence rates were compared between male and female patients using propensity score matching. ResultsPropensity score matching generated 313 matched pairs of patients. Among the entire cohort, the 1-, 3-, and 5-year overall survival and recurrence rates of the male and female patients were 60.2 %, 37.3 %, and 27.7 % vs. 65.8 %, 40.4 %, and 31.0 % (P = 0.380) and 50.6 %, 67.4 %, and 74.2 % vs. 44.4 %, 63.5 %, and 69.6 % (P = 0.123), respectively. In the matched cohort, the 1-, 3-, and 5-year overall survival and recurrence rates of the male and female patients were 60.6 %, 35.9 % and 22.4 % vs. 66.4 %, 40.6 % and 31.1 % (P = 0.041) and 51.5 %, 69.3 % and 83.9 % vs. 44.3 %, 63.6 %, and 69.9 % (P = 0.041), respectively. After adjustment for other confounding variables by multivariate Cox regression analysis, male sex was independently associated with worse overall survival (hazard ratio = 1.322, 95 % confidence interval: 1.079–1.621, P = 0.007) and tumor recurrence (hazard ratio = 1.337, 95 % confidence interval: 1.088–1.645, P = 0.006). A subgroup analysis of patients younger than 55 years old after propensity score matching showed that male patients had significantly worse overall survival and higher recurrence rates than female patients after surgery, while no significant difference in long-term overall survival and recurrence was observed between male and female patients older than 55 years old after propensity score matching. ConclusionMale sex was an independent risk factor for overall survival and tumor recurrence in patients after liver resection for intrahepatic cholangiocarcinoma.

Analysis of risk factors for postoperative recurrence of stage I colorectal cancer: a retrospective analysis of a large population.

Colorectal cancer (CRC) is the third most common cancer worldwide. Patients diagnosed with stage I CRC typically do not require postoperative adjuvant treatment. However, postoperative recurrence is present in at least 40% of patients with CRC and often occurs in those with stage I disease. This study aimed to elucidate the current status of recurrence and clinicopathological characteristics in patients with stage I CRC. Data of indicated patients were obtained from 18 registries in Surveillance, Epidemiology, and End Results (SEER). The multivariable Fine-Gray regression model was used to identify the mortality risk of patients. Disparities in survival were analyzed using Kaplan-Meier curves. Logistic regression was employed to identify factors associated with recurrent risk overestimation. Our study indicated a recurrence rate of 15.04% (1,874/12,452) in stage I CRC cases. Notably, we identified race, age, T stage, and carcinoembryonic antigen (CEA) levels as independent risk factors for tumor recurrence, substantially impacting prognosis. Furthermore, gender, race (Black), age (>65 years), elevated CEA levels, and refusal or unknown status regarding radiotherapy significantly correlated with an adverse prognosis in patients with stage I CRC. We identified certain key clinicopathological features of patients with stage I CRC and demonstrated the survival benefits of radiotherapy, offering a new perspective on stage I CRC follow-up and treatment recommendations.

Analysis of 25 surgical cases of thymic neuroendocrine tumors and thymic carcinoma

BackgroundThe purpose of this study was to evaluate the clinicopathological characteristics of patients who underwent surgical resection for thymic neuroendocrine tumors (TNET) or thymic carcinoma.MethodsIn this study, we retrospectively evaluated the clinicopathological characteristics of our surgical patients at Fukuoka University Hospital from January 1995 to December 2018.ResultsThere were nine cases of TNET and 16 cases of thymic carcinoma. Regarding the pathological type, the TNET group included three atypical carcinoid cases, two large cell neuroendocrine tumor cases, two small cell carcinoma cases, and two other cases. The thymic carcinoma group included 15 squamous carcinoma cases and one case of adenosquamous carcinoma. Based on the Masaoka-Koga staging system, six TNET cases and 11 thymic carcinoma cases were stage III or IV. The complete resection rate was 77% in the TNET group and 81% in the thymic carcinoma group. Additional chemotherapy and/or radiotherapy was performed in five cases of TNET and 11 cases of thymic carcinoma. The five-year survival rate and five-year disease-free survival rate were 87.5% and 75.0% in the TNET group and 58.9% and 57.1% in the thymic carcinoma group, respectively, with no significant difference between the two groups (P = 0.248 and P = 0.894, respectively). In the univariate analysis, complete resection was a statistically significant prognostic factor (P = 0.017).ConclusionIn this study, no difference in prognosis was observed between TNET and thymic carcinomas. To understand the characteristics of these tumors, further case accumulation and multicenter clinical studies are needed. (243words)

Relationship between human epididymal protein 4 and depth of tumor invasion, postoperative recurrence, and metastasis of epithelial epithelial ovarian cancer.

This study aimed to analyze the relationship between human epididymal protein 4 (HE4) and infiltration depth, postoperative recurrence, and metastasis of epithelial ovarian cancer (OVCA). Immunohistochemistry was used to detect the expression level of HE4 in cancer tissues and adjacent tissues of 90 patients with epithelial OVCA admitted to our hospital from May 2017 to January 2018. Cox regression was used to analyze the factors affecting the prognosis of epithelial OVCA. The relationship between HE4 and the prognosis of epithelial OVCA was analyzed by the receiver operating characteristic curve and Kaplan-Meier survival curve. The positive expression rate of HE4 in epithelial OVCA was 85.56%, which was higher than 34.44% in adjacent tissues (p<0.01). The International Federation of Gynecology and Obstetrics stage, infiltration depth, lymph node metastasis, postoperative recurrence and metastasis, and HE4 positivity were independent risk factors for the prognosis, and platinum-based chemotherapy sensitivity was an independent protective factor for the prognosis of patients with epithelial OVCA (p<0.05). The area under the curve of HE4 in diagnosing epithelial OVCA and predicting recurrence was 0.863 and 0.700, the sensitivity was 91.60% and 85.60%, and the specificity was 90.20% and 65.60%. The median progression-free survival and overall survival were 26.1 and 30.2 months in HE4-positive epithelial OVCA patients, while these were 31.4 and 35.6 months in HE4-negative epithelial OVCA patients (p<0.05). In conclusion, HE4 was highly expressed in epithelial OVCA tissues. Its expression level was related to the depth of tumor invasion, postoperative recurrence and metastasis, and other clinicopathological characteristics of patients with epithelial OVCA.

Elective Neck Dissection in cT1-4 N0M0 Head and Neck Basaloid Carcinoma.

To investigate the survival benefit of elective neck dissection (END) over neck observation in surgically resected cT1-4 N0M0 head and neck basaloid carcinoma (HNBC). Retrospective cohort study. The 2006 to 2017 hospital-based National Cancer Database. Patients with surgically resected cT1-4 N0M0 HNBC were selected. Linear, binary logistic, Kaplan-Meier, and Cox proportional hazards regression models were implemented. Of 857 patients satisfying inclusion criteria, the majority were male (77.0%) and white (88.1%) with disease of the oral cavity (21.5%) or oropharynx (42.9%) classified as high grade (76.9%) and cT1-2 (72.9%). 389 (45.4%) patients underwent END. END utilization between 2006 and 2017 increased for cT1-2 disease (33.3% vs56.9%, R2 = .699) but remained relatively constant for cT3-4 disease (66.7% vs57.9%, R2 = .062). One-hundred and fifteen(29.6%) ENDs detected occult nodal metastases (ONMs). The 5-year overall survival (OS) of patients undergoing neck observation and END was 65.6% and 66.8%, respectively (P = .652). END was not associated with improved OS in survival analyses stratified by patient demographics, clinicopathologic features, and adjuvant therapy. Compared with surgery alone, adjuvant radiotherapy (adjusted hazard ratio: 0.74, 95% confidence interval [CI]: 0.57-0.97, P = .031) was associated with improved OS. END (hazard ratio [HR]: 0.96, 95% CI: 0.71-1.28, P = .770) and ONM (HR: 1.12, 95% CI: 0.78-1.61, P = .551) were not associated with OS. END is performed in nearly half of patients with HNBC but is not associated with improved OS, even after stratifying survival analyses by patient demographics, clinicopathologic features, and adjuvant therapy. The rate of ONM approaching 30%, however, justifies inclusion of END in the surgical management of HNBC.

Circ-10720 as a ceRNA adsorbs microRNA-1238 and modulates ZEB2 to boost NSCLC development by activating EMT

BackgroundCircular RNAs (circRNAs) are critical regulators in the progression of tumors. This experimental design aimed to explore the mechanism of circ-10720 in non-small cell lung cancer (NSCLC).MethodsWe used RT-qPCR to measure circ-10720 expression in clinical samples and analyzed its relationship with the clinicopathological characteristics of NSCLC patients. The expression levels of microRNA-1238 (miR-1238) and Zinc Finger E-box-binding Homeobox 2 (ZEB2) in clinical samples were detected by RT-qPCR. NSCLC cells were transfected with relevant plasmids or sequences. Circ-10720, miR-1238, and ZEB2 expressions in cells were analyzed via RT-qPCR or western blot. Cell proliferation, apoptosis, migration, and invasion were assessed with CCK-8, flow cytometry, and transwell assay, respectively. The protein expression of ZEB2 and epithelial–mesenchymal transition (EMT)-related markers (E-cadherin, Vimentin, N-cadherin) were detected via western blot. Xenograft assay was used to determine the effect of circ-10720 on NSCLC in vivo. Circ-10720 and ZEB2 expressions in tumors were detected using RT-qPCR or Western blot. Immunohistochemistry was used to evaluate E-cadherin and N-cadherin expression in tumors. Finally, the binding relationship between miR-1238 with circ-10720 or ZEB2 was verified by the bioinformatics website, dual luciferase reporter assay, RNA pull-down assay, and RIP assay.ResultsCirc-10720 was upregulated in NSCLC and correlated with TNM stage of NSCLC patients. MiR-1238 was lowly expressed but ZEB2 was highly expressed in NSCLC. Circ-10720 silencing suppressed the proliferation, metastasis, and EMT of NSCLC cells. Mechanically, circ-10720 was a competitive endogenous RNA (ceRNA) for miR-1238, and ZEB2 was a target of miR-1238. circ-10720-modulated ZEB2 via competitively binding with miR-1238 to control NSCLC progression. In addition, circ-10720 knockdown suppressed tumor growth in vivo.ConclusionsCirc-10720 acts as a ceRNA to adsorb miR-1238 and modulate ZEB2 to facilitate the proliferation, migration, invasion, and EMT of NSCLC cells.Graphical

Clinical study of the posterior gastric artery and the lymph nodes around it in patients with gastric cancer.

This study aims to gather and analyze the anatomical characteristics of the posterior gastric artery (PGA), investigate the presence and metastasis of lymph nodes around the PGA in patients with gastric cancer. Additionally, the study aims to analyze the relationship between the PGA and its surrounding lymph nodes and the clinicopathological features of patients with gastric cancer. This study consisted of a cross-sectional analysis of data from 52 patients with gastric cancer who underwent total or proximal gastrectomy at the Department of Gastrointestinal Surgery, First Affiliated Hospital of Dalian Medical University, between January 2020 and November 2022. Intraoperative exploration was performed to determine the presence of the PGA, and patients with the PGA were assessed for relevant anatomical characteristics, including the length of the PGA and the distance from the root of the PGA to the celiac trunk. Dissection of lymph nodes around the PGA was also performed. Statistical methods were employed to describe and analyze the data regarding the presence of the PGA, as well as the presence and metastasis of the lymph nodes around the PGA. Additionally, the study identified clinicopathological factors associated with these conditions. The PGA was identified in 39 (75.0%) out of 52 patients with gastric cancer, exhibiting a mean PGA length of 3.5 ± 0.8cm and a mean distance from the root of the PGA to the celiac trunk of 6.7 ± 1.7cm. Among the 39 patients who underwent dissection of lymph nodes around the PGA, 36 lymph nodes around the PGA were detected in 20 patients. Analysis of factors associated with the presence of lymph nodes around the PGA revealed a significant correlation with the macroscopic type of the tumor and the total number of dissected lymph nodes (P = 0.007 and P = 0.022, respectively), with a larger number of total dissected lymph nodes being an independent factor (OR = 1.105, 95%CI: 1.019-1.199, P = 0.016). Furthermore, analysis of risk factors for metastasis of the lymph nodes around the PGA demonstrated that the total number of metastatic lymph nodes, No.3 lymph node metastasis, and No.11 lymph node metastasis were associated with metastasis of the lymph nodes around the PGA (P = 0.043, P = 0.028, and P = 0.020, respectively). The PGA exhibits a high incidence. It is essential to carefully identify the PGA during procedures involving the PGA and consider appropriate preservation or disconnection of this vessel. The presence of lymph nodes around the PGA is not an isolated occurrence. Gastric cancer can result in metastasis of the lymph nodes around the PGA. Although the overall risk of metastasis of the lymph nodes around the PGA is low in patients with gastric cancer, it increases in the presence of conditions such as No.3 lymph node metastasis, No.11 lymph node metastasis, advanced tumor stage, and extensive metastases in other regional lymph nodes.