Transcriptome Analysis in Vulvar Squamous Cell Cancer

Abstract

To date, therapeutic strategies in vulvar squamous cell carcinoma (VSCC) are lacking molecular pathological information and targeted therapy hasn’t been approved in the treatment of VSCC, yet. Two etiological pathways are widely accepted: HPV induced vs. HPV independent, associated with chronic skin disease, often harboring TP53 mutations (mut). The aim of this analysis was to analyze the RNA expression patterns for subtype stratification on VSCC samples that can be integrated into the previously performed whole exome sequencing data for the detection of prognostic markers and potential therapeutic targets. We performed multiplex gene expression analysis (NanoString) with 770 genes in 24 prior next generation sequenced samples. An integrative data analysis was performed. Here, 98 genes were differentially expressed in TP53mut vs. HPV+ VSCC, in the TP53mut cohort, where 56 genes were upregulated and 42 were downregulated in comparison to the HPV+ tumors. Aberrant expression was primarily observed in cell cycle regulation, especially in HPV+ disease. Within the TP53mut group, a distinct cluster was identified that was correlated to a significantly worse overall survival (p = 0.017). The RNA expression profiles showed distinct patterns with regard to the known VSCC subtypes and could potentially enable further subclassification in the TP53mut groups

Management of primary and recurrent Bartholin’s gland carcinoma: A systematic review on behalf of MITO Rare Cancer Group

“…Genomic and molecular profiling of vulvar carcinoma highlighted that the most common types of mutation included PT53, CDKN2A (p16) , and EGFR . 78-80 In vulvar squamous cell carcinoma, EGFR immunohistochemical overexpression/gene amplification has been identified as an early event and linked to poor clinical outcomes, representing a possible target for a therapeutic strategy. 81,82 Recently, a phase II trial evaluated the anti-tumor activity of erlotinib on a cohort of locally advanced, primary, recurrent, or metastatic vulvar squamous cell carcinoma, reaching an overall clinical benefit rate of 67.5%.…”

Immunosuppressive M2 TAMs represent a promising target population to enhance phagocytosis of ovarian cancer cells in vitro

“…The other samples were not matched from the same patients. The RNAseq cohort includes material from 192 ovarian cancer patients who underwent primary debulking surgery according to current German guidelines ( 21 ). Cell aspirates and tumor tissue were obtained before treatment and after written informed consent in accordance with the Declaration of Helsinki and approved by the local ethics board (#200814 and PV6012-4312-BO-ff).…”

“…RNA extraction from tumor tissue of 192 ovarian cancer patients was performed as previously described ( 21 ). Briefly, tissue samples were obtained intraoperatively and immediately stored in liquid nitrogen as fresh frozen samples.…”