Clinicopathological Features Research Articles

Preoperative prediction of HER-2 expression status in breast cancer based on MRI radiomics model

Objective: This study aims to explore the predictive value of T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC), and early-delayed phases enhanced magnetic resonance imaging (DCE-MRI) radiomics prediction model in determining human epidermal growth factor receptor 2 status in breast cancer. Methods: A retrospective study was conducted, involving 187 patients with confirmed breast cancer by postsurgical pathology at Zhenjiang First People's Hospital during January 2021 and May 2023. Immunohistochemistry or fluorescence in situ hybridization was used to determine the HER-2 status of these patients, with 48 cases classified as HER-2 positive and 139 cases as HER-2 negative. The training set was used to construct the prediction models and the validation set was used to verify the prediction models. Layers of T2WI, ADC, and early-delayed phase DCE-MRI images were used to delineate the volumeof interest and 960 radiomic features were extracted from each case using Pyradiomic. After screening and dimensionality reduction by intraclass correlation coefficient, Pearson correlation analysis, least absolute shrinkage, and selection operator, the radiomics labels were established. Logistic regression analysis was used to construct the T2WI radiomics model, ADC radiomics model, DCE-2 radiomics model, DCE-6 radiomics model, and the joint sequence radiomics model to predict the HER-2 expression status of breast cancer, respectively. Based on the clinical, pathological, and MRI image characteristics of patients, univariate and multivariate logistic regression analysis wasused to construct a clinicopathological MRI feature model. The radscore of every patient and the clinicopathological MRI features which were statistically significant after screening were used to construct a nomogram model. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of each model and the decision curve analysis wasused to evaluate the clinical usefulness. Results: The T2WI, ADC, DCE-2, DCE-6, and joint sequence radiomics models, the clinicopathological MRI feature model, and the nomogram model were successfully constructed to predict the expression status of HER-2 in breast cancer. ROC analysis showed that in the training set and validation set, the areas under the curve (AUC) of the T2WI radiomics model were 0.797 and 0.760, of the ADC radiomics model were 0.776 and 0.634, of the DCE-2 radiomics model were 0.804 and 0.759, of the DCE-6 radiomics model were 0.869 and 0.798, of the combined sequence radiomics model were 0.908 and 0.847, of the clinicopathological MRI feature model were 0.703 and 0.693, and of the nomogram model were 0.938 and 0.859, respectively. In the training set, the combined sequence radiomics model outperformed the clinicopathological features model (P＜0.001). In the training and validation sets, the nomogram outperformed the clinicopathological features model (P＜0.05). In addition, the diagnostic performance of the nomogram was better than that of the four single-modality radiomics models in the training cohort (P＜0.05) and was better than that of DCE-2 and ADC models in the validation cohort (P＜0.05). Decision curve analysis indicated that the value of individualized prediction models was higher than clinical and pathological prediction models in clinical practice. The calibration curve showed that the multimodal radiomics model had a high consistency with the actual results in predicting HER-2 expression. Conclusions: T2WI, ADC and early-delayed phase DCE-MRI imaging histology models for HER-2 expression status in breast cancer are expected to provide a non-invasive virtual pathological basis for decision-making on preoperative neoadjuvant regimens in breast cancer.

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.

PD-L1 expression, tumor-infiltrating lymphocytes, and mismatch repair proteins status in digestive neuroendocrine neoplasms: exploring their potential role as theragnostic and prognostic biomarkers.

Theragnostic biomarkers are still needed to select patients with digestive neuroendocrine neoplasms (NENs) for an optimal management. The PD-1/PD-L1 pathway plays a pivotal role in T cells activation and host immune response to cancer and PD-L1 expression in tumor and/or immune cells is used to identify patients who would benefit of treatment with immune checkpoint inhibitors. However, its role as a biomarker is still unclear in digestive NENs. We investigated PD-L1 expression in 68 well-characterized digestive NENs (32 NETs, 32 NECs and 4 MiNENs) and TPS and CPS scores were calculated. In addition, tumor infiltrating T-lymphocytes and mismatch repair protein expression (MMR) were evaluated. All results were correlated with clinicopathological features. PD-L1 expression was higher in NECs than in NETs: TPS > 1% and/or CPS > 1 were observed in 16% of NETs, 68.8% of NECs and 50% of MiNENs (p: 0.05). The mean TPS score in positive cases was 6.3% in NETs, 16.2% in NECs and 5% in MiNENs. The CPS score was 4.8 in NETs, 8.1 in NECs and 6 in MiNENs. MMR-deficient neoplasms were more frequently observed in NECs than in NETs (p: < 0.05) as well as intra-tumor immune infiltration (p: 0.00001). No correlation between PD-L1 expression and survival or other clinicopathological parameters was observed. Our results suggest that treatment with immune checkpoint inhibitors may have a potential role only in selected cases, mainly in NECs and MiNENs.

Prognostic significance and value of further classification of lymphovascular invasion in invasive breast cancer: a retrospective observational study.

To investigate the prognostic significance of lymphovascular invasion in invasive breast cancer and the value of using specific vascular endothelial markers to further classify lymphovascular invasion. We collected 2124 patients with invasive breast cancer who were hospitalized at the First Hospital of Dalian Medical University from 2012 to 2020. Statistical methods were used to investigate the relationship between lymphovascular invasion and clinicopathological characteristics of breast cancer, and the correlation between lymphovascular invasion on overall survival (OS) and disease-free survival (DFS) of various categories of breast cancers. Immunohistochemical staining of breast cancer samples containing lymphovascular invasion using specific vascular endothelial markers D2-40 and CD34 was used to classify lymphovascular invasion and to investigate the relationship between lymphovascular invasion and breast cancer progression. There was a high correlation between lymphovascular invasion and T stage, N stage and nerve invasion. Survival analyses showed that patients with lymphovascular invasion, especially luminal B, triple-negative, and Her-2 overexpression breast cancer patients, had poorer OS and DFS prognosis, and that lymphovascular invasion was an independent prognostic factor affecting OS and DFS in breast cancer. The immunohistochemical staining results showed that positive D2-40 staining of lymphovascular invasion was linked to the N stage and localized recurrence of breast cancer. Lymphovascular invasion is associated with aggressive clinicopathological features and is an independent poor prognostic factor in invasive breast cancer. Breast cancer localized recurrence rate and lymph node metastases are influenced by lymphatic vessel invasion. Immunohistochemical techniques should be added to the routine diagnosis of lymphovascular invasion.

Long- vs short-segment Barrett's esophagus-derived adenocarcinoma: clinical features and outcomes of endoscopic submucosal dissection.

The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups. We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3cm or ≥ 3cm, respectively. Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0min vs. 60.5min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001). The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required.

CBX1 is involved in hepatocellular carcinoma progression and resistance to sorafenib and lenvatinib via IGF-1R/AKT/SNAIL signaling pathway.

Chromobox Homolog 1 (CBX1) plays a crucial role in the pathogenesis of numerous diseases, including the evolution and advancement of diverse cancers. The role of CBX1 in pan-cancer and its mechanism in hepatocellular carcinoma (HCC), however, remains to be further investigated. Bioinformatics approaches were harnessed to scrutinize CBX1's expression profile, its association with tumor staging, and its potential impact on patient outcomes across various cancers. Single-cell RNA sequencing data facilitated the investigation of CBX1 expression patterns at the individual cell level. The CBX1 expression levels in HCC and adjacent non-tumor tissues were quantified through Real-Time Polymerase Chain Reaction (RT-PCR), Western Blotting (WB), and Immunohistochemical analyses. A tissue microarray was employed to explore the relationship between CBX1 levels, patient prognosis, and clinicopathological characteristics in HCC. Various in vitro assays-including CCK-8, colony formation, Transwell invasion, and scratch tests-were conducted to assess the proliferative and motility properties of HCC cells upon modulation of CBX1 expression. Moreover, the functional impact of CBX1 on HCC was further discerned through xenograft studies in nude mice. CBX1 was found to be upregulated in most cancer forms, with heightened expression correlating with adverse patient prognoses. Within the context of HCC, elevated levels of CBX1 were consistently indicative of poorer clinical outcomes. Suppression of CBX1 through knockdown methodologies markedly diminished HCC cell proliferation, invasive capabilities, migratory activity, Epithelial-mesenchymal transition (EMT) processes, and resistance to Tyrosine kinase inhibitors (TKIs). Contrastingly, CBX1 augmentation facilitated the opposite effects. Subsequent investigative efforts revealed CBX1 to be a promoter of EMT and a contributor to increased TKI resistance within HCC cells, mediated via the IGF-1R/AKT/SNAIL signaling axis. The oncogenic activities of CBX1 proved to be attenuable either by AKT pathway inhibition or by targeted silencing of IGF-1R. The broad overexpression of CBX1 in pan-cancer and specifically in HCC positions it as a putative oncogenic entity. It is implicated in forwarding HCC progression and exacerbating TKI resistance through its interaction with the IGF-1R/AKT/SNAIL signaling cascade.

Programmed Cell Death-Related Gene Signature Associated with Prognosis and Immune Infiltration and the Roles of HMOX1 in the Proliferation and Apoptosis were Investigated in Uveal Melanoma.

Uveal melanoma (UVM) is the most common primary ocular malignancy, with a wide range of symptoms and outcomes. The programmed cell death (PCD) plays an important role in tumor development, diagnosis, and prognosis. There is still no research on the relationship between PCD-related genes and UVM. A novel PCD-associated prognostic model is urgently needed to improve treatment strategies. We aim to screen PCD-related prognostic signature and investigate its proliferation ability and apoptosis in UVM cells. The clinical information and RNA-seq data of the UVM patients were collected from the TCGA cohort. All the patients were classified using consensus clustering by the selected PCD-related genes. After univariate Cox regression and PPI network analysis, the prognostic PCD-related genes were then submitted to the LASSO regression analysis to build a prognostic model. The level of immune infiltration of 8-PCD signature in high- and low-risk patients was analyzed using xCell. The prediction on chemotherapy and immunotherapy response in UVM patients was assessed by GDSC and TIDE algorithm. CCK-8, western blot and Annexin V-FITC/PI staining were used to explore the roles of HMOX1 in UVM cells. A total of 8-PCD signature was constructed and the risk score of the PCD signature was negatively correlated with the overall survival, indicating strong predictive ability and independent prognostic value. The risk score was positively correlated with CD8 Tcm, CD8 Tem and Th2 cells. Immune cells in high-risk group had poorer overall survival. The drug sensitivity demonstrated that cisplatin might impact the progression of UVM and better immunotherapy responsiveness in the high-risk group. Finally, Overespression HMOX1 (OE-HMOX1) decreased the cell viability and induced apoptosis in UVM cells. Recuse experiment results showed that ferrostatin-1 (fer-1) protected MP65 cells from apoptosis and necrosis caused by OE-HMOX1. The PCD signature may have a significant role in the tumor microenvironment, clinicopathological characteristics, prognosis and drug sensitivity. More importantly, HMOX1 depletion greatly induced tumor cell growth and inhibited cell apoptosis and fer-1 protected UVM cells from apoptosis and necrosis induced by OE-HMOX1. This work provides a foundation for effective therapeutic strategy in tumour treatment.

A novel tRNA-derived fragment tRF-17-18VBY9M works as a potential diagnostic biomarker for gastric cancer

BackgroundGastric cancer (GC) is one of the most prevalent malignant tumors worldwide. The low effectiveness of common biomarkers for the detection of early GC makes it essential to seek new biomarkers to improve diagnostic efficacy. tsRNAs (transfer RNA-derived small RNAs) are related to the growth of malignant tumors. In this article, we focused on whether tsRNAs may be employed as biomarkers for GC.MethodstRF-17-18VBY9M was screened in the tsRFun database as a research object. The methodological efficacy of tRF-17-18VBY9M was evaluated using Sanger sequencing, agarose gel electrophoresis assays, and gradient dilution. The χ2 test was applied to assess the interaction between tRF-17-18VBY9M expression and clinicopathologic characteristics. The receiver operating characteristic (ROC) curve was utilized to investigate the clinical efficiency of tRF-17-18VBY9M in GC.ResultsThe Chi-square test demonstrated that high-expressed tRF-17-18VBY9M was closely associated with the T stage, tumor node metastasis stage (TNM), lymph node metastasis, and neurological/vascular invasion. ROC curve analysis revealed that the diagnostic value of tRF-17-18VBY9M in GC was superior to carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724).ConclusiontRF-17-18VBY9M is up-regulated in both GC sera and tissues. Differential tRF-17-18VBY9M expression distinguishes GC patients from healthy donors and gastritis patients, which suggests tRF-17-18VBY9M could act as a diagnostic biomarker in GC.

Integrated Clinical Genotype-phenotype Characteristics of STAT3-mutated Myeloid Neoplasms.

STAT3 is a key transcription factor that mediates cancer progression through phosphorylation or gain-of-function mutations. STAT3 activation in myeloid neoplasms (MNs) is primarily mediated through phosphorylation. STAT3 mutation has only rarely been reported in MNs. We assessed the clinicopathologic and molecular genetic features of 32 STAT3-mutated MNs. The frequency of STAT3 mutation in MNs was <0.5%. Twenty (62.5%) cases were classified as acute myeloid leukemia (AML), 7 (21.9%) as myelodysplastic syndrome (MDS), 5 (15.6%) as chronic myelomonocytic leukemia (CMML), but none as myeloproliferative neoplasms (MPN). STAT3 mutations occurred at initial diagnosis in 22 (88%) cases, or at relapse or upon leukemic transformation. Clonal hierarchy analysis revealed that STAT3 mutations represented the dominant clone in 30% of AML cases, but were subclonal in MDS and CMML. Most were missense mutations located at the SH2 domain, Y640F being the most common. STAT3 mutation was accompanied by co-existing mutations in all cases, most frequently SRSF2, TET2, ASXL1, and SETBP1. STAT3 mutations were usually associated with morphologic dysplasia, increased blasts, and monosomy 7/del7q. With a median follow-up of 24.5 months, 21 patients died, 6 had persistent disease, and 5 achieved complete remission after stem cell transplantation. STAT3 mutation is present in various MNs, but not in MPN. It is often an early event or occurs upon leukemic transformation, suggesting an important role in the pathogenesis and progression of MNs by activating JAK-STAT pathway. It may help identify a subset of patients with MNs who may benefit from targeted therapy.

Inflammation-based lung adenocarcinoma molecular subtype identification and construction of an inflammation-related signature with bulk and single-cell RNA-seq data.

The role of inflammation is increasingly understood to have a central influence on therapeutic outcomes and prognosis in lung adenocarcinoma (LUAD). However, the detailed molecular divisions involved in inflammatory responses are yet to be fully elucidated. Our study identified two main inflammation-oriented LUAD grades: the inflammation-low (INF-low) and the inflammation-high (INF-high) subtypes. Both presented with unique clinicopathological features, implications for prognosis, and distinctive tumor microenvironment profiles. Broadly, the INF-low grade, marked by its dominant immunosuppressive tumor microenvironment, was accompanied by less favorable prognostic outcomes and a heightened prevalence of oncogenic mutations. In contrast, the INF-high grade exhibited more optimistic clinical trajectories, underscored by its immune-active environment. In addition, our efforts led to the conceptualization and empirical validation of an inflammation-centric predictive model with considerable predictive potency. Our study paves the way for a refined inflammation-centric LUAD classification and fosters a deeper understanding of tumor microenvironment intricacies.

Impact of thyroid carcinoma invasion of recurrent laryngeal nerve on cervical lymph node metastasis.

Papillary thyroid carcinoma (PTC) has a favorable prognosis. However, involvement of the recurrent laryngeal nerve (RLN) significantly increases the risk of recurrence. RLN invasion was an important factor in determining the extent of thyroid surgery. The purpose of this study was to compare clinicopathologic features and characterize risk factors of central and lateral lymph node metastasis (LLNM) of RLN invasion in patients with PTC. A retrospective review was conducted of 130 patients with PTCs who had exclusive tumor involvement of the RLN at our institution between January 2014 and February 2019. All patients underwent total thyroidectomy and high-dose radioactive iodine (RAI) therapy. The clinicopathologic factors and prognostic outcomes of the patients with solitary and multiple RLN involvements were compared. Kaplan-Meier method was performed to compare the outcomes of tumor recurrence. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with LLNM. The invasion of the RLN was similar on both sides, with 58.5% on the right, 40.0% on the left, and 1.5% on both sides. Significant differences were observed in tumor size (p < 0.001), lymph node metastasis classification (p = 0.002), RLN resection (p < 0.001), and thyroglobulin (p = 0.010) in the solitary and multiple groups. During the median follow-up of 67 months, 9 (6.9%) patients developed recurrence. There were no statistical differences in recurrence for age, tumor size, gender, multifocality, lymph node metastasis (LNM), and RLN resection. According to receiver operating characteristic (ROC) curve analyses, a cut-off of tumor size > 1.7 cm was identified as the most sensitive and specific predictor of RLN with multiple involvements or LNM invasion. Univariate and multivariate analyses revealed that central lymph node metastasis (CLNM) and RLN invasion by LNM can serve as independent risk factors for LLNM (p = 0.006 and p < 0.001, respectively). Our results indicate that recurrence was comparable in patients with solitary and multiple RLN involvements. Multiple RLN involvement was associated with pathological features such as larger tumors, RLN resection, and LLNM. The presence of LNM invading RLN and multiple nerve involvement increases the risk of intraoperative RLN resection. A higher risk of multiple invasion or LNM invasion should be considered when tumor size > 1.7 cm. The presence of CLNM and RLN invaded by LNM were independent predictors for LLNM, which could aid surgeons in deciding on lateral lymph node dissection.

High MAL2 expression predicts shorter survival in women with triple-negative breast cancer.

Due to its lack of conventional surface receptors, triple-negative breast cancer (TNBC) is inherently resistant to most targeted therapies. MAL2 overexpression prompts endocytosis, conferring resistance to novel therapeutics. This study explores the role of MAL2 and PD-L1 in TNBC patients' prognosis. We performed immunohistochemical analysis on 111 TNBC samples collected from 76 patients and evaluated the expression of MAL2 and PD-1. We expanded the study by including The Cancer Genome Atlas (TCGA) cohort. MAL2 expression did not correlate with stage, grade, tumor size, lymph node invasion, metastasis, and PD-1 expression. Patients with high MAL2 had significantly lower 5-year survival rates (71.33% vs. 89.59%, p = 0.0224). In the tissue microarray cohort (TMA), node invasions, size, recurrence, and low MAL2 (HR 0.29 [CI 95% 0.087-0.95]; p < 0.05) predicted longer patients' survival. In the TCGA cohort, patients with low MAL2 had significantly longer overall survival and disease-specific survival than patients with high MAL2. Older age and high MAL2 expression were the only independent predictors of shorter patient survival in the BRCA TCGA cohort. High MAL2 predicts unfavorable prognosis in triple-negative breast cancer, and its expression is independent of PD-1 levels and clinicopathological features of TNBC.

Clinical characteristics and treatment outcomes of patients with IgG4-positive ocular adnexal marginal zone B-cell lymphoma.

To explore the clinicopathological characteristics of immunoglobulin G4 (IgG4)-positive ocular adnexal marginal zone B-cell lymphoma (OAML) and associated patient treatment outcomes. Medical records from patients diagnosed with IgG4-positive OAML treated at the West China Hospital between January 2016 and August 2023 were retrospectively analyzed. This study included data from 22 patients (11 males, 11 females), aged between 36 and 83 years, with disease durations from 1 month to 30 years. Sixteen cases exhibited unilateral ocular involvement (ten left eyes, six right eyes), while six exhibited bilateral involvement. Common clinical symptoms included ocular masses, eyelid swelling, and proptosis, with the orbit and lacrimal gland being the most commonly impacted sites. Among the 22 patients, 13 who were clinically suspected of having IgG4-related ophthalmic disease (IgG4-ROD) underwent serum IgG4 testing pre-operatively, revealing elevated IgG4 levels in 11 of these patients. The use of computed tomography and magnetic resonance imaging facilitated the evaluation of the location and size of lesions. All 22 patients received surgical treatment. Subsequently, 14 of these patients underwent local radiotherapy, five received post-operative chemotherapy, and three were closely observed. The follow-up period of patients in this study was 3-77 months, with an average follow-up time of 36 months. Except for one patient who died of disease progression, all others showed favorable prognoses with significant improvements. These results support the classification of IgG4-positive OAML as a distinct OAML sub-type with clinical features that partially overlap with IgG4-ROD. Therefore, accurate differentiation between OAML and IgG4-ROD is imperative, necessitating timely surgical intervention and precise pathological diagnosis to prevent diagnostic errors and inappropriate treatment. Currently, no standardized treatments for IgG4-positive OAML exist, but our results suggest that standard OAML therapies are generally efficacious.

RAS/RAF mutations and microsatellite instability status in primary colorectal cancers according to HER2 amplification.

HER2 amplification-associated molecular alterations and clinicopathologic features in colorectal cancers (CRCs) have not been well established. In this study, we assessed the prevalence of HER2 amplification and microsatellite instability (MSI) status of 992 patients with primary CRC. In addition, molecular alterations of HER2 amplified and unamplified CRCs were examined and compared by next-generation sequencing. HER2 amplifications were found in 41 (4.1%) of 992 primary CRCs. HER2 amplification was identified in 1.0% of the right colonic tumors, 5.1% of the left colonic tumors, and 4.8% of the rectal tumors. Approximately 95% of HER2 amplification was observed in the left colon and rectum. Seven (87.5%) of eight metastatic tumors showed HER2 amplification. Most clinicopathologic features were unrelated to HER2 amplification except tumor size and MSI status. All 41 HER2 amplified CRCs were microsatellite stable. In a molecular analysis of frequently identified somatic mutations in CRCs, HER2 amplified CRCs showed a lower rate of KRAS mutations (24.4%) but a higher rate of TP53 mutations (83%) than unamplified CRCs. No BRAF and NRAS mutations were identified in HER2 amplified CRCs. Our study suggests that HER2 amplified CRCs are mutually exclusive of MSI and harbor less frequent KRAS/NRAS/BRAF mutations but frequent T53 mutations.

A multi-parametric prognostic model based on clinicopathologic features: vessels encapsulating tumor clusters and hepatic plates predict overall survival in hepatocellular carcinoma patients

BackgroundVessels encapsulating tumor clusters (VETC) is a newly described vascular pattern that is distinct from microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Despite its importance, the current pathological diagnosis report does not include information on VETC and hepatic plates (HP). We aimed to evaluate the prognostic value of integrating VETC and HP (VETC-HP model) in the assessment of HCC.MethodsA total of 1255 HCC patients who underwent radical surgery were classified into training (879 patients) and validation (376 patients) cohorts. Additionally, 37 patients treated with lenvatinib were studied, included 31 patients in high-risk group and 6 patients in low-risk group. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish a prognostic model for the training set. Harrell’s concordance index (C-index), time-dependent receiver operating characteristics curve (tdROC), and decision curve analysis were utilized to evaluate our model's performance by comparing it to traditional tumor node metastasis (TNM) staging for individualized prognosis.ResultsA prognostic model, VETC-HP model, based on risk scores for overall survival (OS) was established. The VETC-HP model demonstrated robust performance, with area under the curve (AUC) values of 0.832 and 0.780 for predicting 3- and 5-year OS in the training cohort, and 0.805 and 0.750 in the validation cohort, respectively. The model showed superior prediction accuracy and discrimination power compared to TNM staging, with C-index values of 0.753 and 0.672 for OS and disease-free survival (DFS) in the training cohort, and 0.728 and 0.615 in the validation cohort, respectively, compared to 0.626 and 0.573 for TNM staging in the training cohort, and 0.629 and 0.511 in the validation cohort. Thus, VETC-HP model had higher C-index than TNM stage system(p < 0.01).Furthermore, in the high-risk group, lenvatinib alone appeared to offer less clinical benefit but better disease-free survival time.ConclusionsThe VETC-HP model enhances DFS and OS prediction in HCC compared to traditional TNM staging systems. This model enables personalized temporal survival estimation, potentially improving clinical decision-making in surveillance management and treatment strategies.

Construction of a nomogram based on clinicopathologic features to predict the likelihood of No. 253 lymph node metastasis in rectal cancer patients.

To explore the high-risk factors for rectal cancer No.253 lymph node metastasis (LNM) and to construct a risk nomogram for the individualized prediction of No.253 LNM. This was a retrospective analysis of 425 patients with rectal cancer who underwent laparoscopic-assisted radical surgery. Independent risk factors for rectal cancer No.253 LNM was identified using multivariate logistic regression analysis, and a risk prediction nomogram was constructed based on the independent risk factors. In addition, the performance of the model was evaluated by discrimination, calibration, and clinical benefit. Multivariate logistic regression analysis showed that No.253 lymphadenectasis on CT (OR 10.697, P < 0.001), preoperative T4-stage (OR 4.431, P = 0.001), undifferentiation (OR 3.753, P = 0.004), and preoperative Ca199 level > 27 U/ml (OR 2.628, P = 0.037) were independent risk factors for No.253 LNM. A nomogram was constructed based on the above four factors. The calibration curve of the nomogram was closer to the ideal diagonal, indicating that the nomogram had a better fitting ability. The area under the ROC curve (AUC) was 0.865, which indicated that the nomogram had high discriminative ability. In addition, decision curve analysis (DCA) showed that the model could show better clinical benefit when the threshold probability was between 1% and 50%. Preoperative No.253 lymphadenectasis on CT, preoperative T4-stage, undifferentiation, and elevated preoperative Ca199 level were found to be independent risk factors for the No.253 LNM. A predictive model based on these risk factors can help surgeons make rational clinical decisions.

Laparoscopic assisted colectomy versus laparoscopic complete colectomy: a cost analysis.

To compare the short-term outcomes and explore the potential economic benefits of laparoscopic-assisted colectomy with extracorporeal anastomosis (LAC/EA) vs. laparoscopic complete colectomy with intracorporeal anastomosis (LCC/IA) for patients with non-metastatic resectable colon cancer. Data of patients who underwent laparoscopic hemicolectomy from January 2017 to March 2023 were collected and analyzed. Propensity score matching (PSM) analyses was carried out to minimize the selection bias. Before PSM, a total of 113 patients met the inclusion criteria (39 in the LCC/IA vs. 74 in the LAC/EA). Clinicopathologic characteristics were comparable except for the median number of removed lymph nodes (P = 0.023). LCC/IA was associated with longer operative time, less intraoperative blood loss, and shorter incision length. The rate of 30-day postoperative complications was similar, but the time to first flatus and soft diet was shorter in the LCC/IA. No deaths were reported in either group within 30days after surgery. Costs of surgical instruments (25,945.8 ± 1,918.0 vs. 23,551.9 ± 2,665.5 RMB; P < 0.01) were higher for the LCC/IA but overall costs were similar (LCC/IA, 43,220.0 ± 4,954.0 vs. LAC/EA, 41,269.2 ± 6,685.9 RMB; P = 0.112). After PSM, 38 patients in the LCC/IA and 63 patients in the LAC/EA were compared. LCC/IA was superior in terms of intraoperative blood loss, incision length, and postoperative functional recovery. There was an extra charge of 2385.0 RMB regarding surgical instruments in the LCC/IA but the overall cost did not reach statistical significance. LCC/IA is a feasible, safe, and cost-effective surgical treatment for patients with non-metastatic resectable colon cancer.

Pre-operative MRI in evaluating pathologic complete response to neoadjuvant chemotherapy in patients with breast cancer: a study focused on influencing factors of baseline clinical-pathological and imaging features

PurposeTo investigate what pre-treatment clinical-pathological features and MRI characteristics influence the performance of breast MRI in assessing the pathologic complete response (pCR) of breast cancer patients to Neoadjuvant Chemotherapy (NAC).MethodsA total of 225 patients with pathologically-confirmed breast cancer who underwent pre- and post-NAC breast MRI between January 2020 and April 2023 were retrospectively analyzed. All patients were categorized into radiologic complete response (rCR) and non-rCR groups based on pre-operative MRI. Univariable and multivariable logistic regression were used to identify independent clinicopathological and imaging features associated with imaging-pathological discordance. The performance of pre-operative MRI for predicting pCR to NAC was assessed according to the baseline characteristics of the clinicopathological data and pre-NAC MRI. In addition, the discrepancy between the pre-operative MRI and post-operative pathological findings was further analyzed by a case-control approach.ResultsAmong 225 patients, 99 (44.0%) achieved pCR after NAC. MRI showed the overall sensitivity of 97.6%, specificity of 58.6%, accuracy of 80.4%, a positive predictive value (PPV) of 75.0%, and a negative predictive value (NPV) of 95.1% in identifying pCR. Of baseline features, presence of ductal carcinoma in situ (DCIS) (OR, 3.975 [95% CI: 1.448–10.908], p = 0.007), luminal B (OR, 5.076 [95% CI: 1.401–18.391], p = 0.013), HER2-enriched subtype (OR, 10.949 [95% CI: 3.262–36.747], p &amp;lt; 0.001), multifocal or multicentric lesions (OR, 2.467 [95% CI: 1.067–5.706], p = 0.035), segmental or regional distribution of NME (OR, 8.514 [95% CI: 1.049–69.098], p = 0.045) and rim enhancement of mass (OR, 4.261 [95% CI: 1.347–13.477], p = 0.014) were significantly associated with the discrepancy between MRI and pathology.ConclusionPresence of DCIS, luminal B or HER2-enriched subtype, multicentric or multifocal lesions, segmental or regional distribution of NME and rim enhancement of mass may lead to a decrease in diagnostic accuracy of MRI in patients of breast cancer treated with NAC.

Short colon syndrome in cats.

Shortening of the colon has been described in cats, but its imaging and clinicopathological features remain poorly understood. Description of the signalment, clinical presentation, imaging, endoscopic and histological features of short colon syndrome in cats. Ninety-three cats diagnosed with short colon. Multi-institutional, descriptive, retrospective case series study. Medical records were searched for a diagnosis of short colon on abdominal ultrasonography, computed tomography, endoscopy, autopsy, or a combination of these modalities. The median age of included cats was 12 years at the time of diagnosis. Diarrhea was the most common clinical sign (60/92; 65%), followed by vomiting (36/92; 39%), weight loss (36/92; 39%), and inappetence (24/92; 26%). Thirteen percent of cats (12/92) had no signs of gastrointestinal disease at the time of diagnosis. In addition to a shortened colonic length, 79% (66/84) of cats had concomitant colonic thickening on ultrasonographic examination. On colonoscopy, mucosal ulcerations of the colonic wall were seen in 39% (9/23) of cats. Histopathologically, all cats but 1 (diagnosed simultaneously with colonic small cell lymphoma) had lymphoplasmacytic colitis, and when small intestinal biopsies were performed, concurrent lymphoplasmacytic enteritis or small cell lymphoma of the small intestine. Lymphoplasmacytic colitis is seen commonly in cats with short colon, suggesting a potential link between these entities.

Extraskeletal Ewing Sarcoma of the Gastrointestinal and Hepatobiliary Tract: Deceptive Immunophenotype Commonly Leads to Misdiagnosis.

Ewing sarcoma (ES) is an uncommon mesenchymal neoplasm that typically develops as a bone mass, although up to 30% arise in extraskeletal sites. ES of the gastrointestinal (GI) and hepatobiliary tract is rare and may be misdiagnosed as other, more common neoplasms that occur in these sites. However, the correct classification of extraskeletal ES is important for timely clinical management and prognostication. We reviewed our experience of ES in the GI and hepatobiliary tract in order to further highlight the clinicopathologic features of these neoplasms and document the potential for misdiagnosis in this setting. The archives and consultation files of 6 academic institutions were retrospectively queried for cases of ES occurring in the GI and hepatobiliary tract. The histologic slides and ancillary studies were reviewed and clinical data were retrieved for each case through the electronic medical records, when available. Twenty-three patients with ES in the GI and/or hepatobiliary tract were identified from 2000 to 2022. Of these, 11 were women and 12 were men with a median age of 38 years (range, 2 to 64). Tumor locations included the pancreas (n=5), liver (n=2), stomach (n=3), colorectum (n=3), and small intestine (n=5), as well as tumors involving multiple organs, pelvis and retroperitoneum (n=5). Tumor size varied between 2cm and 18cm. Twenty were primary and 3 were metastases. Of the 23 cases, only 17% were initially diagnosed as ES. The most common misdiagnoses involved various forms of neuroendocrine neoplasia due to expression of synaptophysin and other neuroendocrine markers (22%). A wide variety of diagnoses including GI stromal tumor was considered due to aberrant CD117 expression (4%). The diagnosis of ES was ultimately confirmed by detection of the EWSR1 rearrangement in 22 cases. The remaining case was diagnosed using traditional immunohistochemistry. Follow-up information was available in 20 cases, with follow-up time varying between 2 and 256 months. Six patients with follow-up died of disease between 6 and 60 months following initial presentation. Our data indicate ES in the GI and hepatobiliary tract is commonly misdiagnosed leading to a delay in therapy. In light of the attendant therapeutic and prognostic implications, ES should be considered in the differential diagnosis of any GI or hepatobiliary tumor with epithelioid and/or small round cell morphology.