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

Deyin Xing*, Yuehua Liu, Hyeon Jin Park, Inji Baek, Hung Tran, Gloria Cheang, Jorge Novo, Jessica Dillon, Andres Matoso, Emily Farmer, Max A. Cheng, Ya Chea Tsai, Kara Lombardo, Michael G. Conner, Russell Vang, Chien Fu Hung, Tzyy Choou Wu, Wei Song

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)67-80
Number of pages14
JournalHuman pathology
StatePublished - Oct 2019


  • Mutations
  • PD-L1
  • Squamous cell carcinoma
  • TP53
  • Vulva

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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