Recurrent genetic alterations and biomarker expression in primary and metastatic squamous cell carcinomas of the vulva.

TitleRecurrent genetic alterations and biomarker expression in primary and metastatic squamous cell carcinomas of the vulva.
Publication TypeJournal Article
Year of Publication2019
AuthorsXing D, Liu Y, Park HJin, Baek I, Tran H, Cheang G, Novo J, Dillon J, Matoso A, Farmer E, Cheng MA, Tsai Y-C, Lombardo K, Conner MG, Vang R, Hung C-F, Wu T-C, Song W
JournalHum Pathol
Volume92
Pagination67-80
Date Published2019 Oct
ISSN1532-8392
Abstract

Using a comprehensive next-generation sequencing pipeline (143 genes), Oncomine Comprehensive v.2, we analyzed genetic alterations on a set of vulvar squamous cell carcinomas (SCCs) with emphasis on the primary and metastatic samples from the same patient, to identify amenable therapeutic targets. Clinicopathologic features were reported and genomic DNA was extracted from 42 paraffin-embedded tumor tissues of 32 cases. PD-L1 expression was evaluated in 20 tumor tissues (10 cases with paired primary and metastatic tumors). Fifteen (88%) of 17 successfully analyzed HPV-unrelated SCCs harbored TP53 mutations. 2 different TP53 mutations had been detected in the same tumor in 4 of 15 cases. Other recurrent genetic alterations in this group of tumors included CDKN2a mutations (41%), HRAS mutations (12%), NOTCH1 mutations (12%) and BIRC3 (11q22.1-22.2) amplification (12%). Six HPV-related tumors harbored PIK3CA, BAP1, PTEN, KDR, CTNNB1, and BRCA2 mutations, of which, one case also contained TP53 mutation. Six cases showed identical mutations in paired primary site and distant metastatic location and four cases displayed different mutational profiles. PD-L1 expression was seen in 6 of 10 primary tumors and all 6 paired cases showed discordant PD-L1 expression in the primary and metastatic sites. Our results further confirmed the genetic alterations that are amenable to targeted therapy, offering the potential for individualized management strategies for the treatment of these aggressive tumors with different etiology. Discordant PD-L1 expression in the primary and metastatic vulvar SCCs highlights the importance of evaluation of PD-L1 expression in different locations to avoid false negative information provided for immunotherapy.

DOI10.1016/j.humpath.2019.08.003
Alternate JournalHum. Pathol.
PubMed ID31437519
PubMed Central IDPMC6864277
Grant ListP50 CA098252 / CA / NCI NIH HHS / United States