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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)67-80
Number of pages14
JournalHuman pathology
Volume92
DOIs
StatePublished - Oct 2019

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Vulva
Squamous Cell Carcinoma
Biomarkers
Mutation
Neoplasms
Paraffin
Immunotherapy
Therapeutics
DNA

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Recurrent genetic alterations and biomarker expression in primary and metastatic squamous cell carcinomas of the vulva. / Xing, Deyin; Liu, Yuehua; Park, Hyeon Jin; Baek, Inji; Tran, Hung; Cheang, Gloria; Novo, Jorge; Dillon, Jessica; Matoso, Andres; Farmer, Emily; Cheng, Max A.; Tsai, Ya Chea; Lombardo, Kara; Conner, Michael G.; Vang, Russell; Hung, Chien Fu; Wu, Tzyy Choou; Song, Wei.

In: Human pathology, Vol. 92, 10.2019, p. 67-80.

Research output: Contribution to journalArticle

Xing, D, Liu, Y, Park, HJ, Baek, I, Tran, H, Cheang, G, Novo, J, Dillon, J, Matoso, A, Farmer, E, Cheng, MA, Tsai, YC, Lombardo, K, Conner, MG, Vang, R, Hung, CF, Wu, TC & Song, W 2019, 'Recurrent genetic alterations and biomarker expression in primary and metastatic squamous cell carcinomas of the vulva', Human pathology, vol. 92, pp. 67-80. https://doi.org/10.1016/j.humpath.2019.08.003
Xing, Deyin ; Liu, Yuehua ; Park, Hyeon Jin ; Baek, Inji ; Tran, Hung ; Cheang, Gloria ; Novo, Jorge ; Dillon, Jessica ; Matoso, Andres ; Farmer, Emily ; Cheng, Max A. ; Tsai, Ya Chea ; Lombardo, Kara ; Conner, Michael G. ; Vang, Russell ; Hung, Chien Fu ; Wu, Tzyy Choou ; Song, Wei. / Recurrent genetic alterations and biomarker expression in primary and metastatic squamous cell carcinomas of the vulva. In: Human pathology. 2019 ; Vol. 92. pp. 67-80.
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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.",
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AU - Baek, Inji

AU - Tran, Hung

AU - Cheang, Gloria

AU - Novo, Jorge

AU - Dillon, Jessica

AU - Matoso, Andres

AU - Farmer, Emily

AU - Cheng, Max A.

AU - Tsai, Ya Chea

AU - Lombardo, Kara

AU - Conner, Michael G.

AU - Vang, Russell

AU - Hung, Chien Fu

AU - Wu, Tzyy Choou

AU - Song, Wei

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