Subtype Of Carcinoma Research Articles

Case report: Tongue metastasis as an initial sign of clear cell renal cell carcinoma and its prognosis

Clear cell renal cell carcinoma (ccRCC) is the most prevalent and lethal subtype of renal cell carcinoma (RCC), characterized by a poor prognosis and a high likelihood of distant metastasis. Nonetheless, metastasis of ccRCC to the tongue remains rare. Diagnosing and planning treatment for patients who initially present with tongue metastasis can be particularly challenging, as few cases have been reported in the literature. We present a case of a 62-year-old man who presented with a painful lump on the right anterior border of his tongue. Histological examination revealed lobulated and nested epithelial cell clusters with moderate dysplasia and frequent mitotic figures within the lamina propria. Immunohistochemistry showed positivity for vimentin, CD10, PAX-8, and epithelial membrane antigen (EMA), but negativity for PAX-2, calponin, S-100 protein, periodic acid-Schiff with diastase (PAS-D), P63, P40, and CK7, confirming the diagnosis of ccRCC metastasis to the tongue. After comprehensive evaluation and multidisciplinary team consultation, the patient underwent cytoreductive nephrectomy (CN), metastasectomy, and targeted therapy. According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, the patient maintained stable disease (SD) during systemic treatment. Unfortunately, treatment was discontinued due to adverse drug reactions, and the patient was transitioned to palliative care. His disease progressed to progressive disease (PD), and he ultimately succumbed to systemic infection, with a progression-free survival (PFS) of approximately 15 months. This case highlights the urgent need for improved therapeutic strategies to manage symptoms and prolong survival in patients with this rare metastatic presentation.

Assessing the Rise in Papillary Thyroid Cancer Incidence: A 38-Year Australian Study Investigating WHO Classification Influence

The incidence of thyroid cancer has shown marked increases globally over recent decades. This study investigated how the incidence of papillary thyroid carcinoma (PTC) subtypes and World Health Organisation (WHO) endocrine tumour classification changes have affected overall thyroid cancer incidence recorded in Australia. Using incidence data from the Australian Institute of Health and Welfare cancer registry (spanning 1982 to 2019), this descriptive epidemiological study employed joinpoint regression analysis to assess temporal trends in thyroid carcinoma incidence, focusing on PTC. Results were then compared with WHO endocrine tumour classification changes over the same period. The results showed increasing trends for the classic PTC subtype over the entire 38-year period and for thyroid microcarcinomas post-2003, while a declining trend for the follicular variant of PTC was observed commencing in 2015. Examination of PTC incidence also revealed distinct changes in trends that align with the WHO classification of papillary microcarcinoma as a subtype in 2004 and the reclassification of some encapsulated follicular variant of PTCs to non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) in 2016/17. Even when taking these WHO classification changes into account, significant increases in PTC over the last three decades are observed. These findings underscore the shifts in classification driven by improving diagnostic clarity influencing thyroid carcinoma incidence patterns. However, thyroid carcinoma cases in Australia have dramatically increased over the last three decades independent of WHO classification changes, suggesting a genuine increase rather than simply being a direct consequence of improved reporting and diagnostics.

Pharmacological Inhibition of MDM2 Induces Apoptosis in p53-Mutated Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) represents the most aggressive breast carcinoma subtype lacking efficient therapeutic options. A promising approach in cancer treatment is the pharmacological inhibition of murine double minute 2 (MDM2)-p53 interaction inducing apoptosis in p53 wild-type tumors. However, the role of MDM2 in TNBC with primarily mutant p53 is not well understood. We here selected the clinical-stage MDM2 inhibitors Idasanutlin and Milademetan and investigated their anti-tumoral effects in TNBC. When we analyzed anti-tumor activity in the TNBC cell lines MDA-MB-231, MDA-MB-436, and MDA-MB-468, cellular viability was efficiently reduced, with half maximal inhibitory concentration (IC50) values ranging between 2.00 and 7.62 µM being up to 11-fold lower compared to the well-characterized non-clinical-stage MDM2 inhibitor Nutlin-3a. Furthermore, caspase-3/7 activity was efficiently induced. Importantly, the IC50 values for MDM2 inhibition were equally observed in HCT116 p53+/+ or HCT116 p53−/− cells. Finally, the IC50 was significantly higher in non-malignant MCF-10A cells than in TNBC cells. Taken together, Idasanutlin and Milademetan show a potent anti-tumor activity in TNBC cell culture models by efficiently inducing tumor cell death via apoptosis. This effect was observed despite an inactivating p53 mutation and was apparently independent of p53 expression. Our data suggest that MDM2 is a promising target in TNBC and clinical-stage MDM2 inhibitors should be further evaluated for their potential therapeutic application.

Diagnostic accuracy of preoperative MRI in assessing macrotrabecular-massive subtype of hepatocellular carcinoma: a systematic review and meta-analysis.

To determine the value of preoperative magnetic resonance imaging (MRI) in predicting macrotrabecular-massive hepatocellular carcinoma (MTM-HCC). A search was conducted on PubMed, Web of Science, Cochrane Library databases, and Embase for studies evaluating the performance of MRI in assessing MTM-HCC. The quality assessment of diagnostic studies (QUADAS-2) tool was used to assess the risk of bias. Diagnostic accuracy measures, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR), were pooled. Summary receiver operating characteristic (SROC) curves with the area under the curve (AUC) were generated. Meta-regression analysis was performed to explore potential sources of heterogeneity. A total of ten eligible studies including 2074 lesions in 2053 patients were analyzed. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.65 (0.52, 0.76), 0.88 (0.80, 0.94), 5.6 (3.70, 8.60), 0.40 (0.30, 0.53), 14 (10, 20), and 0.84 (0.81, 0.87), respectively. High heterogeneity was observed (I2 was 78.61% and 90.95% for sensitivity and specificity, respectively) along with a threshold effect (Spearman's correlation coefficient = 0.927, p < 0.001). Meta-regression analysis demonstrated that the MRI method (radiomics or non-radiomics) affected the heterogeneity. MRI has diagnostic value for MTM-HCC due to its higher specificity and moderate sensitivity, but its clinical application remains suboptimal due to significant heterogeneity. Thus, further prospective studies with large sample sizes are needed to confirm these results. Question What is the value of MRI for preoperatively predicting MTM-HCC? Findings Meta-regression analyses revealed that the MRI method (radiomics or non-radiomics) is a significant factor contributing to heterogeneity. Clinical relevance This study demonstrates the high diagnostic accuracy of MRI for early detection of MTM-HCC, which can assist in guiding individualized management.

IMMUNOHISTOCHEMICAL CHARACTERISTICS OF BASAL CELL CARCINOMA AT NATIONAL HOSPITAL OF DERMATOLOGY AND VENEREOLOGY, VIETNAM

Objective: To investigate the immunohistochemical characteristics of basal cell carcinoma at the National Hospital of Dermatology and Venereology. Methods: A descriptive, cross-sectional, retrospective, and prospective study was conducted on 312 patients diagnosed with basal cell carcinoma at the National Hospital of Dermatology and Venereology from January 2019 to September 2023. Histopathological and immunohistochemical analysis was performed using four immune markers: BerEP4, Bcl-2, p63, and EMA. Results: BerEP4 immunostaining was positive in all 312 cases of basal cell carcinoma, representing various histological subtypes. Bcl-2 immunostaining was also positive in all 312 cases of basal cell carcinoma, with notably stronger expression in peripheral tumor cells compared to the central region. P63 immunostaining yielded positive results in 310 cases of basal cell carcinoma, accounting for 99.4% of the cases studied. EMA immunostaining, on the other hand, was negative in 308 cases of basal cell carcinoma, equivalent to 87.2%. The four cases of EMA-positive basal cell carcinoma were all classified as the histopathological subtype of squamous basal cell carcinoma (within the invasive category). Conclusions: These results suggest that immunohistochemistry with the four immune markers, BerEP4, Bcl-2, p63, and EMA, can be used to support the definitive and differential diagnosis of basal cell carcinoma compared to other cutaneous carcinomas. Received 15 September 2023Revised 26 September 2023Accepted 03 November 2023

Identification of Hepatocellular Carcinoma Subtypes Based on Global Gene Expression Profiling to Predict the Prognosis and Potential Therapeutic Drugs.

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous tumor, and distinguishing its subtypes holds significant value for diagnosis, treatment, and the prognosis. Methods: Unsupervised clustering analysis was conducted to classify HCC subtypes. Subtype signature genes were identified using LASSO, SVM, and logistic regression. Survival-related genes were identified using Cox regression, and their expression and function were validated via qPCR and gene interference. GO, KEGG, GSVA, and GSEA were used to determine enriched signaling pathways. ESTIMATE and CIBERSORT were used to calculate the stromal score, tumor purity, and immune cell infiltration. TIDE was employed to predict the patient response to immunotherapy. Finally, drug sensitivity was analyzed using the oncoPredict algorithm. Results: Two HCC subtypes with different gene expression profiles were identified, where subtype S1 exhibited a significantly shorter survival time. A subtype scoring formula and a nomogram were constructed, both of which showed an excellent predictive performance. COL11A1 and ACTL8 were identified as survival-related genes among the signature genes, and the downregulation of COL11A1 could suppress the invasion and migration of HepG2 cells. Subtype S1 was characterized by the upregulation of pathways related to collagen and the extracellular matrix, as well as downregulation associated with the xenobiotic metabolic process and fatty acid degradation. Subtype S1 showed higher stromal scores, immune scores, and ESTIMATE scores and infiltration of macrophages M0 and plasma cells, as well as lower tumor purity and infiltration of NK cells (resting/activated) and resting mast cells. Subtype S2 was more likely to benefit from immunotherapy. Subtype S1 appeared to be more sensitive to BMS-754807, JQ1, and Axitinib, while subtype S2 was more sensitive to SB505124, Pevonedistat, and Tamoxifen. Conclusions: HCC patients can be classified into two subtypes based on their gene expression profiles, which exhibit distinctions in terms of signaling pathways, the immune microenvironment, and drug sensitivity.

Prognostic value of intraductal carcinoma subtypes and postoperative radiotherapy for localized prostate cancer

BackgroundIntraductal carcinoma of the prostate cancer (IDC-P), as a specific pathological type in prostate cancer which usually implies a poor prognosis. IDC-P morphology can be divided into two subtypes: Pattern 1, sieve like or loose cribriform structures; Pattern 2, solid or dense cribriform structures. The purpose of the study is to identify the impact of IDC-P and its subtypes on the prognosis of patients undergoing post-operative radiotherapy (PORT) after radical prostatectomy (RP) due to localized prostate cancer(PCa).MethodsWe performed a retrospective study of patients with localized PCa treated by RP followed by PORT or not. Patients with localized PCa who underwent RP from August 2013 to December 2020 were included in this study. Inclusion criteria: post-operative PSA dropped to less than 0.1 ng/ml after RP, had at least 1 poor prognostic risk factor (including high Gleason’s grouping; positive surgical margins; seminal vesicle invasion; extraprostatic extension; and lympho-vascular invasion), and were eligible for adjuvant radiotherapy.; In this study, patients who underwent salvage radiotherapy after RP due to biochemical recurrence (two consecutive PSA > 0.2 ng/ml) were also included, but not patients with persistent postoperative PSA > 0.1 ng/ml. Exclusion criteria: patients using other types of therapy prior to biochemical recurrence. Screening cases with pathological results of intraductal carcinoma, subtyping was completed by a pathologist, grouped by intraductal carcinoma (+/-; pattern 1/ 2) and treatment regimen (RP + PORT / RP only), Kaplan-Meier curves were plotted based on the time to biochemical recurrence-free and overall survival of the patients, and Cox regression analyses were performed. Finally, based on the results of Cox regression analysis, we initially predicted the probability of biochemical recurrence and death of the patients by plotting the nomogram.ResultsA total of 139 patients were included in this study with a median follow-up of 61.5 months. K-M curves showed that patients with “IDC-P (+) RP only” had the worst prognosis; patients with IDC-P could have a survival benefit after receiving PORT; whereas patients with non-intraductal carcinoma had a better prognosis than the above patients with or without PORT. In addition, patients with IDC-P(+) pattern 2 were more likely to experience biochemical recurrence and death. Multivariate Cox regression analysis showed that pattern 2 was a risk factor for biochemical recurrence and death. Other BCR-related risk factors in the research: Gleason grading group 5 (HR = 3.343, 95% CI: 1.616–6.916, P = 0.001), PM (HR = 2.124, 95% CI: 1.044–4.320,P = 0.038) and PORT (HR = 0.266, 95%CI: 0.109–0.647, P = 0.004). Other OS-related risk factors in the research: Grading group 5 (HR = 3.642, 95%CI:1.475–8.991, P = 0.005), SVI (HR = 2.522, 95% CI: 1.118–5.691, P = 0.026) and PORT (HR = 0.319, 95%CI: 0.107–0.949, P = 0.040).ConclusionPatients suffering from localized prostate cancer with IDC-P(+), especially IDC-P pattern 2, are more susceptible to biochemical recurrence and death after radical prostatectomy. While postoperative radiotherapy can alleviate the negative prognostic impact from IDC-P. It is implied that IDC-P can also be an indicator to be considered in PORT decision making to some extent.

Claudin 18.2 Expression in 1,404 Digestive Tract Adenocarcinomas including 1,175 Colorectal Carcinomas: Distinct Colorectal Carcinoma Subtypes are Claudin 18.2 Positive.

Claudin 18.2 (CLDN18.2) immunohistochemical expression can be used to select patients with gastric/gastroesophageal junction adenocarcinomas for zolbetuximab (IMAB362) therapy, a monoclonal antibody targeting CLDN18.2. The aim of this study was to correlate immunohistochemical expression of CLDN18.2 with clinicopathologic and molecular features in a large series of digestive tract cancers. Immunohistochemistry (IHC) for CLDN18.2 was performed on tissue microarrays from 1404 adenocarcinomas including 155 gastric/gastroesophageal, 74 pancreatic ductal, 1175 colorectal (576 in initial test cohort; 599 in subsequent validation cohort), and correlated with HER2 and mismatch repair (MMR) status. Cases were scored as CLDN18.2 positive or negative, with positivity defined as moderate to strong membranous staining in >75% of tumor cells. CLDN18.2 expression was correlated with clinicopathologic and molecular features for all colorectal adenocarcinomas. CLDN18.2 was positive in 39% (61/155) of gastric/gastroesophageal adenocarcinomas, 38% (28/74) of pancreatic ductal adenocarcinomas, and 3.4% (40/1175) of colorectal adenocarcinomas (p<0.001). For gastric/gastroesophageal and pancreatic ductal adenocarcinoma, there was no correlation between CLDN18.2 expression and either HER2 or MMR status. In contrast, CLDN18.2-positive colorectal adenocarcinomas had distinct clinicopathologic and molecular features. CLDN18.2-positive colorectal adenocarcinomas were more frequently proximally located and were more often MMR deficient and BRAF V600E positive (all with p<0.05). Quantitative pathologic analysis using the digital pathology biomarker QuantCRC demonstrated marked differences in histologic features between CLDN18.2-positive and negative colorectal adenocarcinomas, with CLDN18.2-positive tumors having increased tumor:stroma ratio and %mucin but decreased %immature stroma in both the test and validation cohorts (all with p<0.05). In conclusion, CLDN18.2-positive colorectal adenocarcinomas are frequently MMR deficient, BRAF V600E mutated, and demonstrate distinct histologic features. Future studies addressing the efficacy of zolbetuximab therapy in this subset of colorectal cancers are needed.

Molecular subtype of ovarian clear cell carcinoma: an analysis of 80 Chinese patients using the TCGA molecular classification of endometrial cancer

Molecular subtype of ovarian clear cell carcinoma: an analysis of 80 Chinese patients using the TCGA molecular classification of endometrial cancer

Ringed with complexity: Insights from a difficult signet ring cell urachal carcinoma case

Introduction: Signet ring cell carcinoma is a rare and highly malignant subtype of urachal carcinoma, an already rare type of bladder malignancy. Case Report: We present a case of a 55-year-old male with mucus-like umbilical discharge and a palpable mass with an indeterminate workup found to have signet ring cell carcinoma after surgical intervention. Two months later, recurrence was suspected, and additional surgical intervention was performed. Conclusion: This case emphasizes the challenges in diagnosis, importance of early diagnosis and intervention, and the need for a standardized therapeutic regimen.

Ovarian Carcinomas: Clinicopathologic and Molecular Features With Comments on 2014 FIGO Staging.

According to histopathology and molecular genetics, there are 5 major subtypes of ovarian carcinomas: high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3% to 4%), and low-grade serous (<5%) carcinomas. These tumors, which constitute over 95% of cases, represent distinct diseases with different prognoses and therapy. This review outlines contemporary advances in molecular pathology, which have expanded our knowledge of the biology of epithelial ovarian cancer and are also important to patient management. We also comment on some controversial points of the FIGO staging classification that we proposed in 2014.

Identification of IGFBP3 and LGALS1 as potential secreted biomarkers for clear cell renal cell carcinoma based on bioinformatics analysis and machine learning.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC). Due to the lack of symptoms until advanced stages, early diagnosis of ccRCC is challenging. Therefore, the identification of novel secreted biomarkers for the early detection of ccRCC is urgently needed. This study aimed to identify novel secreted biomarkers for diagnosing ccRCC using bioinformatics and machine learning techniques based on transcriptomics data. Differentially expressed genes (DEGs) in ccRCC compared to normal kidney tissues were identified using 3 transcriptomics datasets (GSE53757, GSE40435 and GSE11151) from the Gene Expression Omnibus (GEO). Potential secreted biomarkers were examined within these common DEGs using a list of human secretome proteins from The Human Protein Atlas. The recursive feature elimination (RFE) technique was used to determine the optimal number of features for building classification machine learning models. The expression levels and clinical associations of candidate biomarkers identified with RFE were validated using transcriptomics data from The Cancer Genome Atlas (TCGA). Classification models were then developed based on the expression levels of these candidate biomarkers. The performance of the models was evaluated based on accuracy, evaluation metrics, confusion matrices, and ROC-AUC (receiver operating characteristic-area under the ROC curve) curves. We identified 44 DEGs that encode potential secreted proteins from 274 common DEGs found across all datasets. Among these, insulin-like growth factor binding protein 3 (IGFBP3) and lectin, galactoside-binding, soluble, 1 (LGALS1) were selected for further analysis using the RFE technique. Both IGFBP3 and LGALS1 showed significant upregulation in ccRCC tissues compared to normal tissues in the GEO and TCGA datasets. The results of the survival analysis indicated that patients with higher expression levels of these genes exhibited shorter overall and disease-free survival times (OS and DFS). Decision tree and random forest models based on IGFBP3 and LGALS1 levels achieved an accuracy of 98.04% and an AUC of 0.98. This study identified IGFBP3 and LGALS1 as promising novel secreted biomarkers for ccRCC diagnosis.

Triple-Negative Breast Cancer: Radiologic-Pathologic Correlation.

Triple-negative breast cancers (TNBCs) are invasive carcinomas that lack ER and PR expression and also lackamplification or overexpression of HER2. Triple-negative breast cancers are histopathologically diverse, with the majority classified as invasive breast carcinomas of no special type with a basal-like profile. Triple-negative breast cancer is the most aggressive molecular subtype of invasive breast carcinoma, with thehighest rates of stage-matched mortality and regional recurrence. Triple-negative breast cancer has a younger median age of diagnosis than other molecular subtypes and is disproportionately diagnosed in Black women and BRCA1 germline pathogenic mutation carriers. On US and mammography, TNBCs are most often seen as a noncircumscribed mass without calcifications; TNBCs can have circumscribed margins and mimic a cyst or have probably benign features that may result in delayed diagnosis. MRI is the most sensitive modality for detecting TNBC, with rim enhancement being a common feature, and MRI is also the most accurate imaging for assessing neoadjuvant chemotherapy response. Understanding the radiologic and pathologic findings of TNBC can aid in diagnosis.

Leveraging explainable AI and large-scale datasets for comprehensive classification of renal histologic types

Recently, as the number of cancer patients has increased, much research is being conducted for efficient treatment, including the use of artificial intelligence in genitourinary pathology. Recent research has focused largely on the classification of renal cell carcinoma subtypes. Nonetheless, the broader categorization of renal tissue into non-neoplastic normal tissue, benign tumor and malignant tumor remains understudied. This gap in research can primarily be attributed to the limited availability of extensive datasets including benign tumor and normal tissue in addition to specific type of renal cell carcinoma, which hampers the ability to conduct comprehensive studies in these broader categories. This research introduces a model aimed at classifying renal tissue into three primary categories: normal (non-neoplastic), benign tumor, and malignant tumor. Utilizing digital pathology while slide images (WSIs) from nephrectomy specimens of 2,535 patients from multiple institutions, the model provides a foundational approach for distinguishing these key tissue types. The study utilized a dataset of 12,223 WSIs comprising 1,300 WSIs of normal tissue, 700 WSIs of benign tumors, and 10,223 WSIs of malignant tumors. Employing the ResNet-18 architecture and a Multiple Instance Learning approach, the model demonstrated high accuracy, with F1-scores of 0.934 (CI: 0.933–0.934) for normal tissue, 0.684 (CI: 0.682–0.687) for benign tumors, and 0.878 (CI: 0.877–0.879) for malignant tumors. The overall performance was also notable, achieving a weighted average F1-score of 0.879 (CI: 0.879–0.880) and a weighted average area under the receiver operating characteristic curve of 0.969 (CI: 0.969–0.969). This model significantly aids in the swift and accurate diagnosis of renal tissue, encompassing non-neoplastic normal tissue, benign tumor, and malignant tumor.

The X-Linked Tumor Suppressor TSPX Regulates Genes Involved in the EGFR Signaling Pathway and Cell Viability to Suppress Lung Adenocarcinoma.

Background: TSPX is an X-linked tumor suppressor that was initially identified in non-small cell lung cancer (NSCLC) cell lines. However, its expression patterns and downstream mechanisms in NSCLC remain unclear. This study aims to investigate the functions of TSPX in NSCLC by identifying its potential downstream targets and their correlation with clinical outcomes. Methods: RNA-seq transcriptome and pathway enrichment analyses were conducted on the TSPX-overexpressing NSCLC cell lines, A549 and SK-MES-1, originating from lung adenocarcinoma and squamous cell carcinoma subtypes, respectively. In addition, comparative analyses were performed using the data from clinical NSCLC specimens (515 lung adenocarcinomas and 502 lung squamous cell carcinomas) in the Cancer Genome Atlas (TCGA) database. Results: TCGA data analysis revealed significant downregulation of TSPX in NSCLC tumors compared to adjacent non-cancerous tissues (Wilcoxon matched pairs signed rank test p < 0.0001). Notably, the TSPX expression levels were inversely correlated with the cancer stage, and higher TSPX levels were associated with better clinical outcomes and improved survival in lung adenocarcinoma, a subtype of NSCLC (median survival extended by 510 days; log-rank test, p = 0.0025). RNA-seq analysis of the TSPX-overexpressing NSCLC cell lines revealed that TSPX regulates various genes involved in the cancer-related signaling pathways and cell viability, consistent with the suppression of cell proliferation in cell culture assays. Notably, various potential downstream targets of TSPX that correlated with patient survival (log-rank test, p = 0.016 to 4.3 × 10-10) were identified, including EGFR pathway-related genes AREG, EREG, FOSL1, and MYC, which were downregulated. Conclusions: Our results suggest that TSPX plays a critical role in suppressing NSCLC progression by downregulating pro-oncogenic genes, particularly those in the EGFR signaling pathway, and upregulating the tumor suppressors, especially in lung adenocarcinoma. These findings suggest that TSPX is a potential biomarker and therapeutic target for NSCLC management.

TP53 Mutations and PD-L1 Amplification in Vulvar Adenocarcinoma of the Intestinal Type: Insights From Whole Exome Sequencing of 2 Cases.

Vulvar adenocarcinoma of the intestinal type (VAIt) is a rare subtype of primary vulvar carcinoma, with ∼30 cases documented in the English literature. This study presents 2 new cases of HPV-independent VAIt with lymph node metastasis and discusses their clinical presentation, histopathologic features, and whole exome sequencing (WES) analysis. Both cases exhibited histologic features consistent with VAIt, including tubular, papillary, and mucinous carcinoma components. Immunohistochemical analysis showed p16 patchy staining, CDX2, CK20, and SATB2 positivity, while being negative for ER, PAX8, and CK7. WES revealed pathogenic TP53 mutations in both cases, accompanied by distinct additional mutations (GRIN2A and KDM6A in Case #1; CHD4 in Case #2). Common copy number alterations (CNAs) included TP53 loss of heterozygosity and CD274/PD-L1 amplification. However, other CNAs varied between the cases. Immunohistochemistry for p53 suggests the presence of both wild-type and mutant subclones, indicating that TP53 abnormalities may be acquired during tumor progression. Both tumors showed mutational signatures SBS1 and SBS5, associated with aging and DNA damage. Our findings deepen the understanding of the genetic events involved in the tumorigenesis of HPV-independent VAIt. Given the TP53 abnormalities and CD274/PD-L1 amplification, emerging p53-based therapies and immune checkpoint inhibitors may represent potential treatment targets. While these findings contribute to the understanding of VAIt tumorigenesis, further research is required to validate these observations in a larger cohort.

SEPT5 overexpression predicts poor prognosis and promotes progression through feedback regulation of HIF-1α in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC), a predominant subtype of renal cell carcinoma, significantly contributes to the heightened morbidity and mortality in individuals diagnosed with urologic tumors. The challenges posed by high malignancy at the initial diagnosis of ccRCC, therapeutic resistance, and unfavorable patient prognosis remain largely unresolved. Our findings indicate that SEPT5 is upregulated in ccRCC and this upregulation is associated with an adverse prognosis for ccRCC patients. Furthermore, we demonstrate that overexpression of SEPT5 promotes proliferation of ccRCC cells, alters their cell cycle distribution, and enhances their migratory and invasive capabilities. Additionally, we observe a positive correlation between SEPT5 overexpression and resistance to sorafenib and sunitinib in ccRCC cells. Further mechanistic investigations have revealed that SEPT5 serves as a novel direct transcriptional target of HIF-1α, leading to subsequent reduction in protein expression and nuclear translocation of HIF-1α. This establishes a feedback loop in ccRCC tumorigenesis. Ultimately, knockdown of SEPT5 significantly inhibits xenografted tumor growth in vivo. Overall, this study provides compelling evidence that directly targeting the HIF-1α-SEPT5 feedback axis may be an effective approach for suppressing the proliferation and progression of ccRCC, offering new insights into the diagnosis and treatment of ccRCC patients.

Surgical Management of Giant Basal Cell Carcinoma in the Maxillofacial Region: Ablative and Reconstructive Strategies.

Giant basal cell carcinoma (GBCC) is a rare and aggressive subtype of basal cell carcinoma (BCC), characterized by a diameter of ≥5 cm and a potential for deep tissue invasion. This study aimed to present our experience with the surgical management of GBCC in the maxillofacial region, focusing on resection and immediate reconstruction strategies. We conducted a retrospective analysis of 5926 patients with BCC in the maxillofacial region from 2010 to 2020, with a specific emphasis on 32 patients diagnosed with GBCC. Associations between patient and tumor characteristics were analyzed, treatment approaches evaluated, and clinical outcomes assessed. The cohort comprised 20 males (62.5%) and 12 females (37.5%) (P > 0.05), with a median age of 71 years (range: 40-86 years). The median time from tumor onset to presentation was 4 years (range: 2-7 years). A total of 24 GBCCs (75%) developed de novo, whereas 8 (25%) were recurrent BCCs (P < 0.05). The median tumor diameter was 8 cm (range: 5-15 cm), with local invasiveness extending to cartilage in 31.25% of cases, facial muscles in 29.41%, neural tissues in 21.87%, and bone in 18.75%. Surgical resections included orbital exenteration (3 cases, 9.38%), total parotidectomy (2 cases, 6.25%), partial maxillectomy (2 cases, 6.25%), frontal craniofacial resection (2 cases, 6.25%), partial petrosectomy with mastoidectomy (1 case, 3.13%), and near-total rhinectomy (1 case, 3.13%). For reconstruction, a skin graft was used in 3 patients (9.38%), local skin flaps in 15 (46.88%), locoregional flaps in 10 (31.25%), and free flaps in 4 (12.5%). The 5-year overall survival, disease-free survival, and disease-specific survival for the cohort were 87.5%, 93.75%, and 96.88%, respectively. Our findings suggest that a single-stage procedure featuring aggressive surgical resection and reconstruction achieves low complication rates, excellent oncologic control, and acceptable cosmetic outcomes.

Comparative Analysis of Transcriptomic and Proteomic Expression between Two Non-Small Cell Lung Cancer Subtypes.

Non-small cell lung cancer (NSCLC) is frequently diagnosed late and has poor survival. The two predominant subtypes of NSCLC, adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), are currently differentially diagnosed using immunohistochemical markers; however, they are increasingly recognized as very different cancer types suggestive of potential for new, more targeted therapies. There are extensive efforts to find more precise and noninvasive differential diagnostic tools. Here, we examined these two NSCLC subtypes for differences that may inform treatment and identify potential novel therapeutic pathways. We presented a comparative analysis of transcriptomic and proteomic expression in tumors from a cohort of 22 NSCLC patients: 8 LUSC and 14 LUAD. Comparing NSCLC subtypes, we found differential gene expression related to cell differentiation for LUSC and cellular structure and immune response regulation for LUAD. Differential protein expression between NSCLC subtypes was related to extracellular structure for LUSC and metabolic processes, including glucose metabolism for LUAD. This direct comparison was more informative about subtype-specific pathways than between each subtype and control (nontumor) tissues. Many of our observations between NSCLC subtypes support and inform existing observations and reveal differences that may aid research seeking to identify and validate novel subtype biomarkers or druggable targets.

FKBP Prolyl Isomerase 11: A Novel Oncogene Interacting With SRSF1 in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the main subtypes of esophageal carcinoma with high morbidity. This study aimed to explore the role of FKBP prolyl isomerase 11 (FKBP11) in ESCC and investigate the underlying mechanism. FKBP11 levels in ESCC tumor tissues and cell lines were measured. Cell function assays were conducted to evaluate the role of FKBP11 in ESCC cells. The xenograft mouse model was established to validate the effect of FKBP11 on ESCC tumorigenesis in vivo. The co-immunoprecipitation assay was performed to determine the FKBP11-interacting proteins. Obvious upregulations in FKBP11 expression were found in ESCC tumor tissues and cell lines. In vitro, FKBP11 knockdown weakened cell proliferation, migration, and invasion capacities and reinforced cell apoptosis in ESCC cells. In vivo, FKBP11 knockdown slowed ESCC tumorigenesis. The following mechanism investigation determined serine and arginine-rich splicing factor 1 (SRSF1) as the FKBP11-interacting protein in ESCC cells. FKBP11 directly bound to SRSF1 and FKBP11 knockdown decreased SRSF1 mRNA level. SRSF1 overexpression abrogated the inhibitory effect of FKBP11 knockdown on the proliferation and migration of ESCC cells. KBP11 functions as an oncogene in ESCC by targeting SRSF1.