Clinicopathological Features Research Articles

Genomic landscape defines peritoneal metastatic pattern and related target of peritoneal metastasis in colorectal cancer.

The primary objective of this study is to develop a prediction model for peritoneal metastasis (PM) in colorectal cancer by integrating the genomic features of primary colorectal cancer, along with clinicopathological features. Concurrently, we aim to identify potential target implicated in the peritoneal dissemination of colorectal cancer through bioinformatics exploration and experimental validation. By analyzing the genomic landscape of primary colorectal cancer and clinicopathological features from 363 metastatic colorectal cancer patients, we identified 22 differently distributed variables, which were used for subsequent LASSO regression to construct a PM prediction model. The integrated model established by LASSO regression, which incorporated two clinicopathological variables and seven genomic variables, precisely discriminated PM cases (AUC 0.899; 95% CI 0.860-0.937) with good calibration (Hosmer-Lemeshow test p = .147). Model validation yielded AUCs of 0.898 (95% CI 0.896-0.899) and 0.704 (95% CI 0.622-0.787) internally and externally, respectively. Additionally, the peritoneal metastasis-related genomic signature (PGS), which was composed of the seven genes in the integrated model, has prognostic stratification capability for colorectal cancer. The divergent genomic landscape drives the driver genes of PM. Bioinformatic analysis concerning these driver genes indicated SERINC1 may be associated with PM. Subsequent experiments indicate that knocking down of SERINC1 functionally suppresses peritoneal dissemination, emphasizing its importance in CRCPM. In summary, the genomic landscape of primary cancer in colorectal cancer defines peritoneal metastatic pattern and reveals the potential target of SERINC1 for PM in colorectal cancer.

Detection and identification of circulating tumor cells in parathyroid tumors and correlation analysis with clinicopathological features.

The differential diagnosis of parathyroid carcinoma (PC)/parathyroid adenoma (PA) in parathyroid tumors is critical for their management and prognosis. Circulating tumor cells (CTCs) identification in the peripheral blood of parathyroid tumors remains unknown. In this study, we proposed to investigate the differences of CTCs in PC/PA and the relationship with clinicopathologic features to assess its relevance to PC and value in identifying PC/PA. Peripheral blood was collected from 27 patients with PC and 37 patients with PA treated in our hospital, and the number of chromosome 8 aberrant CTCs was detected by negative magnetic bead sorting fluorescence in situ hybridization (NE-FISH). The differences of CTCs in PC/PA peripheral blood were compared and their diagnostic efficacy was evaluated, and the correlation between CTCs and clinicopathological features of PC was further explored. CTCs differed significantly in PC/PA (p = 0.0008) and were up-regulated in PC, with good diagnostic efficacy. CTCs combined with alkaline phosphatase (ALP) assay improved the diagnostic efficacy in identifying PC/PA (AUC = 0.7838, p = 0.0001). The number of CTCs was correlated with tumor dimensions, but not significantly correlated with clinical markers such as calcium and PTH and pathological features such as vascular invasion, lymph node metastasis and distant metastasis. As a non-invasive liquid biopsy method, CTCs test combined with ALP test can be used as an important reference basis for timely and accurate identification and treatment of PC. It is of great significance to improve the current situation of PC diagnosis, treatment and prognosis.

Prognostic Significance of Nuclear Factor kappa B (p65) among Breast Cancer Patients in Cape Coast Teaching Hospital.

Breast cancer is the most prevalent cancer among African women, with high mortality rates in Ghana. Nuclear factor kappa B (NF-kB) has been associated with tumor progression in breast cancer. However, its clinical validation is controversial and understudied with no known published data on NF-kB (p65) among breast cancer patients in Ghana and other African countries. This study assessed the prognostic significance of NF-kB(p65) expression and its association with various clinicopathological features in breast cancer patients. 90 formalin-fixed breast cancer tissues and 15 normal breast tissues were used to determine the expression of NF-kB (p65) using immunohistochemistry. We explored the correlation between expression of NF-kB (p65) and clinicopathological features. NF-kB (p65) was expressed in 86.7% of breast cancer tissues. There was a significant relationship between NF-kB (p65) expression and tumor grade, proliferation index (Ki67), and molecular subtype. High NF-kB (p65) expression in tumor grade 3 was about 10 times that of grade 1 (54.2% versus 5.1%), and Ki67 > 20 was 79.7% compared to 20.3% for Ki67 ≤ 20. Patients with triple-negative breast cancer (TNBC) had 49.1% overexpression of NF-kB (p65) compared to 17%, 25.4% and 8.5% for luminal A, luminal B, and HER 2 cases respectively. This study demonstrates that NF-kB (p65) was highly expressed among breast cancer patients at Cape Coast Teaching Hospital, Ghana especially in TNBC. NF-kB (p65) could serve as a biomarker for cancer stage, progression, prognosis, and as a therapeutic target.

Clinical Significance of Primary Tumor Resection in Perihilar Cholangiocarcinoma with Positive Peritoneal Lavage Cytology.

The prognostic impact of positive peritoneal lavage cytology (CY+) in patients with perihilar cholangiocarcinoma (PHC) remains unclear. The present study investigated the clinical significance of primary tumor resection of CY+ PHC. We retrospectively evaluated 282 patients who underwent surgery for PHC between September 2002 and March 2022. The patients' clinicopathological characteristics and survival outcomes were compared between the CY negative (CY-) resected (n = 262), CY+ resected (n = 12), and CY+ unresected (n = 8) groups. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival. The expected residual liver volume was significantly higher in the CY+ resected group (61%) than in the CY- resected (47%) and CY+ unresected (37%) groups (p = 0.004 and 0.007, respectively). The CY+ resected group had a higher administration rate of postoperative therapy than the CY- resected group (58% vs. 16%, p = 0.002). Overall survival of the CY+ resected group was similar to that of the CY- resected group (median survival time [MST] 44.5 vs. 44.6, p = 0.404) and was significantly better than that of the CY+ unresected group (MST 44.5 vs. 17.1, p = 0.006). CY positivity was not a prognostic factor according to a multivariate analysis in patients with primary tumor resection. The CY+ resected group showed better survival than the CY+ unresected group and a similar survival to that of the CY- resected group. Resection of the primary tumor with CY+ PHC may improve the prognosis in selected patients.

Clinicopathological Differences between Right and Left Colorectal Cancer by Sex

Background: Until now, studies on colorectal cancer (CRC) have focused on clinicopathological characteristics based on location without considering sex differences. However, as men and women have fundamentally different physiological characteristics, research results in the clinical field are limited. We aimed to elucidate the differences in the clinicopathological characteristics between right-sided CRC (RCC) and left-sided CRC (LCC) according to sex. Methods: We classified 1492 South Korean patients with no history of colon surgery between July 2005 and June 2015 based on tumor location and sex. For these patients, differences in the clinical characteristics according to sex were compared using univariate and multivariate analyses. Results: Of the 1269 patients, 951 (74.9%) had LCC, and 318 (25.1%) had RCC, making LCC approximately three times more common than RCC. When sex was not taken into account, patients with RCC had significantly higher rates of anemia and undifferentiated cancers than the rates in those with LCC. Even considering sex, anemia and undifferentiated cancer were more prevalent in RCC than in LCC in both men and women. In contrast, age over 65 years and abnormal white blood cell count differed between RCC and LCC only in women. Conclusions: The clinicopathologic characteristics of CRC vary according to the location and sex. Therefore, sex must be considered as a fundamental characteristic of personalized treatment.

Identification of the new molecular subtypes related to inflammation in breast cancer.

Breast cancer is a prevalent ailment among women, and the inflammatory response plays a crucial role in the management and prediction of breast cancer (BRCA). However, the new subtypes based on inflammation in BRCA research are still undefined. The databases including The Cancer Genome Atlas and gene expression omnibus were utilized to gather clinical data and somatic mutation information for approximately 1069 BRCA patients. Through Consensus Clustering, novel subtypes linked to inflammation were identified. A comparative analysis was conducted on the prognosis, and immune cell infiltration, and somatic mutation of the new subtypes. Additionally, an investigation into drug therapy and immunotherapy was conducted to distinguish high-risk individuals from low-risk ones. The findings of this investigation proposed the categorization of BRCA into innovative subtypes predicated on the inflammatory response and 6 key genes were a meaningful approach. Specifically, the low-, medium-, and high-inflammation subtypes exhibited varying degrees of association with clinicopathological features, tumor microenvironment, and prognosis. Notably, the high-inflammation subtype was characterized by a strong correlation with immunosuppressive microenvironments and a higher frequency of somatic mutations, which was an indication of poorer health. This study revealed that a brand-new classification could throw new light on the effective prognosis. The integration of multiple key genes was a new characterization that could promote more immunotherapy strategies and contribute to predicting the efficacy of the chemotherapeutic drugs.

Primary colon lymphomas: An analysis of our experience over the last 18 years.

Colon lymphoma is a rare type of gastrointestinal lymphoma and represents 0.2% to -1.2% of all primary colon cancers. This study aimed to retrospectively examine the general characteristics, treatment methods, and survival characteristics of patients with colon lymphoma who were followed-up at our center. This retrospective study included patients diagnosed with colon lymphoma who were followed up at Ankara Numune Training and Research Hospital and Ankara Bilkent City Hospital between December 2005 and June 2023. Clinicopathological features, radiological findings, treatments, and modalities of patients were obtained from their medical records. Fourteen patients with primary colon lymphoma were included in the study. Thirteen patients (92.9%) were diagnosed with diffuse large B-cell lymphoma. The median age of the patients was 55 (28-84) years. The tumor location was the terminal ileum/cecum in 50% of the patients. At the time of diagnosis, 10 patients (7 with stage 1E-2E disease, 2 with stage 3E disease, and 1 with stage 4E disease due to tumor obstruction) underwent surgery. Twelve patients received chemotherapy (6 patients as adjuvant and 6 patients as first-line treatment). The median overall survival (OS) was 10 years (0.1-21.5) years, the 5-year median OS was 71%, and the 10-year median OS was 53%. Primary colon lymphoma is a rare disease and its optimal treatment is not clearly defined. The primary treatment for primary colon lymphoma is a combination of surgery and chemotherapy. A clear consensus on the treatment can be established through prospective studies.

Complete Laparoscopic Type C2 Radical Surgery for Cervical Stump Cancer: No-Look and No-Touch Techniques.

Due to previous surgical history and subsequent adhesions between pelvic organs, surgery for cervical stump cancer (CSC) is technically more challenging than surgery for cervical cancer with an intact uterus.1 We aimed to illustrate the related anatomy, surgical steps and techniques of complete laparoscopic type C2 radical surgery (CLRS) for early-stage CSC. CLRS for six patients with CSC was performed from January 2021 to January 2022. We demonstrated the detailed skills of parametrial management during CLRS for CSC in case 5 by means of a video. A 58-year-old woman diagnosed with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIA1 CSC received CLRS through five operative ports (Fig.1). The magnetic resonance imaging (MRI) scans and gross appearance of the specimen are shown in Fig.2. The median age and body mass index (BMI) of the six patients were 53 years and 23.8, respectively. The median blood loss was 275mL; the median time of operation was 218min; the median length of hospitalization was 15 days; and the median time to recover urinary function was 12 days. One patient underwent postoperative radiation for pathologically proven adenocarcinoma with deep stromal invasion,2 while the other five did not. After a median follow-up of 24 months, no patients experienced complications, recurrence, or death (Table 1). This study details the skills of CLRS for CSC, especially space development and the 'no-look, no-touch' tumor-free principle. It is helpful for clinicians to perform safe and standardized surgery on patients with early-stage CSC. Fig.1 Trocar placement of complete laparoscopic type C2 radical surgery for early-stage CSC. CSC cervical stump cancer, S superior, I inferior, R right, L left, U umbilicus Fig.2 MRI scans and gross appearance of the specimen for case 5 with CSC at FIGO 2018 stage IIA1. The tumor lesion on the cervical stump is indicated by yellow arrows. a Axial T2-weighted image; b DKI image; c ADC map; d sagittal T2-weighted image; e sagittal T1-weighted image; f gross appearance of the surgical specimen. MRI magnetic resonance imaging, CSC cervical stump cancer, FIGO International Federation of Gynecology and Obstetrics, DKI diffusional kurtosis imaging, ADC apparent diffusion coefficient Table 1 Clinicopathological characteristics, operative details, and outcomes of patients with cervical stump cancer Patient no. Age at diagnosis (years) BMI Reasons for subtotal hysterectomy FIGO 2018 stage Histology Operation Operation time (mins) Blood loss (mL) Urinary catheter (days) Hospital stay (days) Complications Depth of invasion LVSI LNs dissected TNM stage Tumor size (mm) Postoperative radiotherapy Follow-up (months) Recurrence Death 1 50 25.9 Uterine myoma IIA1 ASC CLRS+PLND 221 360 10 12 No Middle one-third N 13 T2a1N0M0 16 No 30 No No 2 55 17.3 Uterine myoma IB1 AC CLRS+PLND 191 270 20 12 No Deep one-third N 24 T1b1N0M0 10 Yes 20 No No 3 50 24.8 Uterine myoma IB1 SC CLRS+PLND 295 310 13 15 No Superficial one-third N 21 T1b1N0M0 15 No 25 No No 4 63 30.1 Uterine myoma IB1 SC CLRS+PLND 213 180 6 16 No Superficial one-third N 25 T1b1N0M0 15 No 19 No No 5 58 20.2 Postpartum hemorrhage IIA1 SC CLRS+PLND 220 100 11 14 No Middle one-third N 21 T2a1N0M0 15 No 24 No No 6 46 22.7 Uterine myoma IB1 SC CLRS+PLND 215 120 14 17 No Superficial one-third N 26 T1b1N0M0 12 No 23 No No BMI body mass index, FIGO International Federation of Gynecology and Obstetrics, ASC cervical adenosquamous carcinoma, AC cervical adenocarcinoma, SC cervical squamous carcinoma, CLRS+PLND complete laparoscopic radical surgery and pelvic node dissections, LVSI lymphovascular space invasion, N negative, LNs lymph nodes, TNM tumor node metastasis.

Neoadjuvant chemotherapy is associated with improved disease-free survival in pancreatic cancer patients undergoing pancreaticoduodenectomy with vascular resection.

Neoadjuvant chemotherapy (NAC) is becoming favored for all pancreatic adenocarcinoma (PDAC). Patients with seemingly resectable disease infrequently still display vascular involvement intraoperatively. Outcomes following NAC versus upfront surgery in patients undergoing pancreaticoduodenectomy (PD) with vascular resection are unknown. We performed a retrospective cohort study of PDAC patients who underwent PD with vascular resection between January 1, 2013, to December 31, 2020, within a single academic center. Clinicopathologic characteristics and disease-free survival (DFS) were compared between NAC versus upfront surgery cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. Eighty-one patients who underwent PD with vascular resection for PDAC were included. Forty-six patients (56%) received NAC. The NAC cohort more often had pathologic N0 status (47.8% vs. 8.6%, p < 0.001), had decreased vascular invasion (11% vs. 40%, p = 0.002), and completed chemotherapy (80% vs. 40%, p < 0.01). The NAC cohort demonstrated improved DFS (40.5 vs. 14.3 months, p = 0.007). In multivariable analysis, NAC remained independently associated with increased DFS (HR = 0.48, p = 0.02). NAC was associated with improved clinicopathologic outcomes and DFS in PD with vascular resection. These findings demonstrate the advantage of NAC in PDAC patients undergoing PD with vascular resection.

Do we need reshape rTNM staging system for ipsilateral breast tumor recurrence of breast cancer? A population-based, propensity score matched cohort study.

The aim of the study was to explore the role of recurrent TNM (rTNM) staging in predicting prognosis for ipsilateral breast tumor recurrence (IBTR) and determine the optimal treatment strategy for IBTR. IBTR cases were identified from the Surveillance, Epidemiology, and End Results (SEER) database spanning the years 2000-2018. Cox proportional hazards analysis was performed to examine factors associated with overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) was employed to match IBTR with primary early breast cancer (EBC) based on clinicopathological characteristics. Investigations into the impact of different therapies were also included. Of the 4375 IBTR cases included in the study, the 5-year OS was 87.1%, 71.6% and 58.7% in rTNM stages I, II and III, respectively. After PSM, while IBTR patients had worse survival to primary EBC patients, prognosis of IBTR for different rTNM stage always closely aligned with the corresponding stage of primary EBC. Repeat breast-conserving surgery (BCS) with radiation therapy was equivalent to mastectomy with respect to OS and BCSS. Chemotherapy was favorable for OS and BCSS in estrogen receptor (ER)-negative IBTR or IBTR occurring within a 60-month interval. rTNM staging system has an outstanding prognostic value for survival outcome of patients with IBTR, and IBTR and primary EBC may have potentially analogous features in the context of TNM staging. BCS plus radiation therapy may be an alternative. IBTR cases who have experienced recurrence with short intervals and with ER-negative tumors might benefit from chemotherapy.

A rare case of TFEB/6p21/VEGFA-amplified renal cell carcinoma diagnosed by whole-exome sequencing: clinicopathological and genetic feature report and literature review

BackgroundTFEB/6p21/VEGFA-amplified renal cell carcinoma (RCC) is rare and difficult to diagnose, with diverse histological patterns and immunohistochemical and poorly defined molecular genetic characteristics.Case presentationWe report a case of a 63-year-old male admitted in 2017 with complex histomorphology, three morphological features of clear cell, eosinophilic and papillary RCC and resembling areas of glomerular and tubular formation. The immunophenotype also showed a mixture of CD10 and P504s. RCC with a high suspicion of collision tumors was indicated according to the 2014 WHO classification system; no precise diagnosis was possible. The patient was diagnosed at a different hospital with poorly differentiated lung squamous cell carcinoma one year after RCC surgery. We exploited molecular technology advances to retrospectively investigate the patient’s molecular genetic alterations by whole-exome sequencing. The results revealed a 6p21 amplification in VEGFA and TFEB gene acquisition absent in other RCC subtypes. Clear cell, papillary, chromophobe, TFE3-translocation, eosinophilic solid and cystic RCC were excluded. Strong TFEB and Melan-A protein positivity prompted rediagnosis as TFEB/6p21/VEGFA-amplified RCC as per 2022 WHO classification. TMB-L (low tumor mutational load), CCND3 gene acquisition and MRE11A and ATM gene deletion mutations indicated sensitivity to PD-1/PD-L1 inhibitor combinations and the FDA-approved targeted agents Niraparib (Grade C), Olaparib (Grade C), Rucaparib (Grade C) and Talazoparib (Class C). GO (Gene Ontology) and KEGG enrichment analyses revealed major mutations and abnormal CNVs in genes involved in biological processes such as the TGF-β, Hippo, E-cadherin, lysosomal biogenesis and autophagy signaling pathways, biofilm synthesis cell adhesion substance metabolism regulation and others. We compared TFEB/6p21/VEGFA-amplified with TFEB-translocated RCC; significant differences in disease onset age, histological patterns, pathological stages, clinical prognoses, and genetic characteristics were revealed.ConclusionWe clarified the patient’s challenging diagnosis and discussed the clinicopathology, immunophenotype, differential diagnosis, and molecular genetic information regarding TFEB/6p21/VEGFA-amplified RCC via exome analysis and a literature review.

The RTK–RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/FUS::ERG

Acute myeloid leukemia (AML) with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis. However, its clinical and molecular features remain poorly defined. We determined the clinicopathological, genomic, and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center. Thirty-six AML patients harboring FUS::ERG were identified, with an incidence rate of 0.3%. These patients were characterized by high lactate dehydrogenase levels (median: 838.5 U/L), elevated bone marrow blast counts (median: 71.5%), and a CD56-positive immunophenotype (94.3%). Notably, we found that RTK–RAS GTPase (RAS) pathway genes, including NRAS (33%) and PTPN11 (24%), were frequently mutated in this subtype. Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt (PI3K-Akt), mitogen-activated protein kinase (MAPK), and RAS signaling pathways and upregulation of BCL2, the target of venetoclax, in FUS::ERG AML compared to RUNX1::RUNX1T1 AML, a more common AML subtype with good prognosis. The median event-free survival in patients with FUS::ERG AML was 11.9 (95% confidence interval [CI]: 9.0–not available [NA]) months and the median overall survival was 18.2 (95% CI: 12.4–NA) months. Allogeneic hematopoietic stem cell transplantation failed to improve outcomes. Overall, the high incidence of RTK–RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.

A cross-sectional study of ERG expression and the relationship with clinicopathological features of Prostate cancer in Southwestern Uganda

BackgroundProstate cancer is the leading cause of cancer-related death and the second most commonly diagnosed cancer among men in Uganda and most countries in Sub-Saharan Africa (SSA). The TMPRSS2-ERG fusion gene is the most common genetic alteration seen among prostate cancer patients. There are several contradicting reports about the association of ERG protein with poor prognosis, high PSA, and Gleason score. This study determined the prevalence of ERG expression and the relationship with PSA, Gleason score, and Age of prostate cancer patients in Southwestern Uganda.MethodsWe reviewed 130 archived prostate biopsy (needle and TURP) specimens from patients of age ≥ 50 years who had a histological diagnosis of prostate cancer. We obtained their biodata, and preoperative PSA, from the archived records. We did Immunohistochemistry (IHC) to determine the prevalence of ERG expression.ResultsThe mean patient age in our study was 74.64 ± 10.19 years. Pre-operative PSA levels had been done for 79.2% of the participants. Most cancers (58.46%) were of high grade (grade group 3–5). ERG expression prevalence was 75.4% and its expression was independent of age, re-operative PSA, and Gleason score.ConclusionThere is a significantly higher prevalence of ERG expression in our study compared to what is reported in other African-based studies. The expression of the ERG is independent of age, Gleason score, and serum PSA levels. A high proportion of our prostate cancer has high-grade disease at the time of diagnosis.

Clinical calculator based on CT and clinicopathologic characteristics predicts short-term prognosis following resection of microsatellite-stabilized diffuse gastric cancer.

Although microsatellite stability/Epithelial-mesenchymal transition (MSS/EMT) subtypes have been reported in multiple cancer prognosis studies, strong confounding factors between MSS/EMT (usually with Lauren's diffuse phenotype) and diffuse gastric cancer (GC) may obscure the independent prognostic value of diffuse GC. Additionally, recent studies suggest a strong correlation between mural stratification based on CT and diffuse GC. This study aims to investigate potential prognostic factors of MSS diffuse GC using mural stratification and to develop a risk assessment model. This retrospective study included 131 patients with MSS diffuse GC who underwent radical surgery. Univariate and multivariate Cox proportional hazards regression analysis was used to identify model predictors and construct a nomogram for overall survival (OS) and recurrence-free survival (RFS) risks. The model's performance was evaluated using ROC, accuracy, and C-index. Internal validation of the model was conducted using the bootstrap resampling method. Among 131 cases, 60 cases (45.8%) exhibited grade 2 mural stratification, which correlated with a poorer tumor prognosis and a more invasive phenotype. Furthermore, a nomogram for predicting OS and RFS prognosis was established based on multivariate results (age, extranodal invasion, mural stratification, and/or P53). The nomogram demonstrated excellent performance, with an AUC of 0.859 (95% CI 0.794-0.924) for OS and 0.859 (95% CI 0.789-0.929) for RFS. Internal validation using 1000 bootstrap samples yielded AUC values of 0.845 and 0.846 for OS and RFS, respectively. Grade 2 mural stratification based on CT imaging revealed a more aggressive invasive phenotype, characterized by increased LN metastasis, higher rates of peritoneal metastasis, and a poorer short-term prognosis. Furthermore, the CT phenotype-based nomogram demonstrates favorable discrimination and calibration, enabling convenient individual short-term prognostic evaluation following resection of MSS diffuse GC.

Comparative Analysis of Clinicopathologic Characteristics and Outcomes of Urothelial Bladder Cancer Between Young and Older Adults—Experience from a Tertiary Care Center

Comparative Analysis of Clinicopathologic Characteristics and Outcomes of Urothelial Bladder Cancer Between Young and Older Adults—Experience from a Tertiary Care Center

The Impact of the Coexpression of MET and ESR Genes on Prognosticators and Clinical Outcomes of Breast Cancer: An Analysis for the METABRIC Dataset

Purpose. Breast cancer is a heterogeneous disease. Exploring new prognostic and therapeutic targets in patients with breast cancer is essential. This study investigated the expression of MET, ESR1, and ESR2 genes and their association with clinicopathologic characteristics and clinical outcomes in patients with breast cancer. Methods. The METABRIC dataset for breast cancer was obtained from the cBioPortal public domain. Gene expression data for MET, ESR1, and ESR2, as well as the putative copy number alterations (CNAs) for MET were retrieved. Results. The MET mRNA expression levels correlated inversely with the expression levels of ESR1 and positively with the expression levels of ESR2 (r = −0.379, p&lt;0.001 and r = 0.066, and p=0.004, respectively). The ESR1 mRNA expression was significantly different among MET CNAs groups p&lt;0.001. Patients with high MET/ESR1 coexpression had favorable clinicopathologic tumor characteristics and prognosticators compared to low MET/ESR1 coexpression in terms of greater age at diagnosis, reduced Nottingham Prognostic Index, lower tumor grade, hormone receptor positivity, HER2-negative status, and luminal subtype p&lt;0.001. In contrast, patients with high MET/ESR2 coexpression had unfavorable tumor features and advanced prognosticators compared to patients with low MET/ESR2 coexpression p&lt;0.001. No significant difference in overall survival was observed based on the MET/ESR coexpression status. However, when data were stratified based on the treatment type (chemotherapy and hormonal therapy), survival was significantly different based on the coexpression status of MET/ESR. Conclusions. Findings from our study add to the growing evidence on the potential crosstalk between MET and estrogen receptors in breast cancer. The expression of the MET/ESR genes could be a novel prognosticator and calls for future studies to evaluate the impact of combinational treatment approaches with MET inhibitors and endocrine drugs in breast cancer.

Non-intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses: an analysis of clinical characteristics and prognosis

Non-intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses: an analysis of clinical characteristics and prognosis

Declination of Treatment, Racial and Ethnic Disparity, and Overall Survival in US Patients With Breast Cancer

Declining treatment negatively affects health outcomes among patients with cancer. Limited research has investigated national trends of and factors associated with treatment declination or its association with overall survival (OS) among patients with breast cancer. To examine trends and racial and ethnic disparities in treatment declination and racial and ethnic OS differences stratified by treatment decision in US patients with breast cancer. This retrospective cross-sectional study used data for patients with breast cancer from the 2004 to 2020 National Cancer Database. Four treatment modalities were assessed: chemotherapy, hormone therapy (HT), radiotherapy, and surgery. The chemotherapy cohort included patients with stage I to IV disease. The HT cohort included patients with stage I to IV hormone receptor-positive disease. The radiotherapy and surgery cohorts included patients with stage I to III disease. Data were analyzed from March to November 2023. Race and ethnicity and other sociodemographic and clinicopathologic characteristics. Treatment decision, categorized as received or declined, was modeled using logistic regression. OS was modeled using Cox regression. Models were controlled for year of initial diagnosis, age, sex, health insurance, median household income, facility type, Charlson-Deyo comorbidity score, histology, American Joint Committee on Cancer stage, molecular subtype, and tumor grade. The study included 2 837 446 patients (mean [SD] age, 61.6 [13.4] years; 99.1% female), with 1.7% American Indian, Alaska Native, or other patients; 3.5% Asian or Pacific Islander patients; 11.2% Black patients; 5.6% Hispanic patients; and 78.0% White patients. Of 1 296 488 patients who were offered chemotherapy, 124 721 (9.6%) declined; 99 276 of 1 635 916 patients (6.1%) declined radiotherapy; 94 363 of 1 893 339 patients (5.0%) declined HT; and 15 846 of 2 590 963 patients (0.6%) declined surgery. Compared with White patients, American Indian, Alaska Native, or other patients (adjusted odds ratio [AOR], 1.47; 95% CI, 1.26-1.72), Asian or Pacific Islander patients (AOR, 1.29; 95% CI, 1.15-1.44), and Black patients (AOR, 2.01; 95% CI, 1.89-2.14) were more likely to decline surgery; American Indian, Alaska Native, or other patients (AOR, 1.13; 95% CI, 1.05-1.21) and Asian or Pacific Islander patients (AOR, 1.21; 95% CI, 1.16-1.27) were more likely to decline chemotherapy; and Black patients were more likely to decline radiotherapy (AOR, 1.05; 95% CI, 1.02-1.08). Asian or Pacific Islander patients (AOR, 0.81; 95% CI, 0.77-0.85), Black patients (AOR, 0.86; 95% CI, 0.83-0.89), and Hispanic patients (AOR, 0.66; 95% CI, 0.63-0.69) were less likely to decline HT. Furthermore, Black patients who declined chemotherapy had a higher mortality risk than White patients (adjusted hazard ratio [AHR], 1.07; 95% CI, 1.02-1.13), while there were no OS differences between Black and White patients who declined HT (AHR, 1.05; 95% CI, 0.97-1.13) or radiotherapy (AHR, 0.98; 95% CI, 0.92-1.04). This cross-sectional study highlights racial and ethnic disparities in treatment declination and OS, suggesting the need for equity-focused interventions, such as patient education on treatment benefits and improved patient-clinician communication and shared decision-making, to reduce disparities and improve patient survival.

Cutaneous Squamous Cell Carcinoma: An Updated Review

Representing the second most common skin cancer, the incidence and disease burden of cutaneous squamous cell carcinoma (cSCC) continues to increase. Surgical excision of the primary site effectively cures the majority of cSCC cases. However, an aggressive subset of cSCC persists with clinicopathological features that are indicative of higher recurrence, metastasis, and mortality risks. Acceleration of these features is driven by a combination of genetic and environmental factors. The past several years have seen remarkable progress in shaping the treatment landscape for advanced cSCC. Risk stratification and clinical management is a top priority. This review provides an overview of the current perspectives on cSCC with a focus on staging, treatment, and maintenance strategies, along with future research directions.

Evaluating the utility of ZNF331 promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance)

ABSTRACT While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of ZNF331 promoter hypermethylation (mZNF331) as a prognostic and predictive marker in colon cancer. We examined the association of mZNF331 with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803). Residual tumour tissue was available for genomic DNA extraction and methylation analysis for 385 patients. ZNF331 promoter methylation status was determined by bisulphite conversion and fluorescence-based real-time polymerase chain reaction. Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive role of mZNF331 in this well-annotated dataset, adjusting for clinicopathologic features and standard molecular markers. mZNF331 was observed in 267/385 (69.4%) evaluable cases. Histopathologic features were largely similar between patients with mZNF331 compared to unmethylated ZNF331 (unmZNFF31). There was no significant difference in disease-free or overall survival between patients with mZNF331 versus unmZNF331 colon cancers, even when adjusting for clinicopathologic features and molecular marker status. Similarly, there was no difference in disease-free or overall survival across treatment arms when stratified by ZNF331 methylation status. While ZNF331 promoter hypermethylation is frequently observed in CRC, our current study of a small subset of patients with stage III colon cancer suggests limited applicability as a prognostic marker. Larger studies may provide more insight and clarity into the applicability of mZNF331 as a prognostic and predictive marker.