Marguerite L Palisoul1, Mary M Mullen1, Rebecca Feldman2, Premal H Thaker3. 1. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, Alvin J. Siteman Cancer Center, St Louis, MO, United States. 2. Department of Solid Tumor Oncology, Carolinas HealthCare System, Levine Cancer Institute, Charlotte, NC, United States. 3. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, Alvin J. Siteman Cancer Center, St Louis, MO, United States. Electronic address: thakerp@wudosis.wustl.edu.
Abstract
OBJECTIVES: To identify molecular alterations that contribute to vulvar cancer pathogenesis with the intent of identifying molecular targets for treatment. METHODS: After retrospective analysis of a database of molecularly-profiled gynecologic cancer patients, 149 vulvar cancer patients were included and tested centrally at a CLIA laboratory (Caris Life Sciences, Phoenix, AZ). Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and gene amplification (C/FISH). A Fisher's exact test was used when indicated with a p-value≤0.05 indicating significance. RESULTS: Median age was 65. 85% had squamous cell carcinoma (SCC) and 15% adenocarcinoma (ADC) histologies. 46% had metastatic (Stage IV) disease. Targeted hot-spot sequencing identified variants in the following genes: TP53 (33%), PIK3CA/BRCA2 (8%, 10%, respectively), HRAS/FBXW7 (5%, 4%, respectively) and ERBB4/GNAS (3%, 3% respectively). Mutations in AKT1, ATM, FGFR2, KRAS, NRAS (n=1, respectively) and BRAF (n=2) also occurred. Specific protein changes for targetable genes included clinically pathogenic mutations commonly found in other cancers (e.g. PIK3CA: exon 9 [E545K], RAS: G13D, Q61L, BRCA2: S1667X, BRAF: R443T, FBXW7: E471fs, etc.). Drug targets identified by IHC and ISH methodologies include cMET (32% IHC, 2% ISH), PDL1 (18%), PTEN loss (56%), HER2 (4% IHC, 2% ISH) and hormone receptors (AR, 4%; ER, 11%; PR, 4%). Comparisons between SCC and ADC identified differential rates for AR, ER, HER2 and GNAS with an increased presence in ADC (p-values all <0.05). CONCLUSIONS: Molecularly-guided precision medicine could provide vulvar cancer patients alternative, targeted treatment options.
OBJECTIVES: To identify molecular alterations that contribute to vulvar cancer pathogenesis with the intent of identifying molecular targets for treatment. METHODS: After retrospective analysis of a database of molecularly-profiled gynecologic cancerpatients, 149 vulvar cancerpatients were included and tested centrally at a CLIA laboratory (Caris Life Sciences, Phoenix, AZ). Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and gene amplification (C/FISH). A Fisher's exact test was used when indicated with a p-value≤0.05 indicating significance. RESULTS: Median age was 65. 85% had squamous cell carcinoma (SCC) and 15% adenocarcinoma (ADC) histologies. 46% had metastatic (Stage IV) disease. Targeted hot-spot sequencing identified variants in the following genes: TP53 (33%), PIK3CA/BRCA2 (8%, 10%, respectively), HRAS/FBXW7 (5%, 4%, respectively) and ERBB4/GNAS (3%, 3% respectively). Mutations in AKT1, ATM, FGFR2, KRAS, NRAS (n=1, respectively) and BRAF (n=2) also occurred. Specific protein changes for targetable genes included clinically pathogenic mutations commonly found in other cancers (e.g. PIK3CA: exon 9 [E545K], RAS: G13D, Q61L, BRCA2: S1667X, BRAF: R443T, FBXW7: E471fs, etc.). Drug targets identified by IHC and ISH methodologies include cMET (32% IHC, 2% ISH), PDL1 (18%), PTEN loss (56%), HER2 (4% IHC, 2% ISH) and hormone receptors (AR, 4%; ER, 11%; PR, 4%). Comparisons between SCC and ADC identified differential rates for AR, ER, HER2 and GNAS with an increased presence in ADC (p-values all <0.05). CONCLUSIONS: Molecularly-guided precision medicine could provide vulvar cancerpatients alternative, targeted treatment options.
Authors: Simona Maria Fragomeni; Frediano Inzani; Anna Fagotti; Luigi Della Corte; Stefano Gentileschi; Luca Tagliaferri; Gian Franco Zannoni; Giovanni Scambia; Giorgia Garganese Journal: J Cancer Res Clin Oncol Date: 2020-04-25 Impact factor: 4.553
Authors: Kelly Pedrozo Ferreira; Bruna Cristine de Almeida; Laura Gonzalez Dos Anjos; Glauco Baiocchi; Fernando Augusto Soares; Rafael Malagoli Rocha; Edmund Chada Baracat; Andrey Senos Dobroff; Katia Candido Carvalho Journal: Int J Mol Sci Date: 2021-05-09 Impact factor: 5.923
Authors: Erik A Williams; Adrienne J Werth; Radwa Sharaf; Meagan Montesion; Ethan S Sokol; Dean C Pavlick; Molly McLaughlin-Drubin; Rachel Erlich; Helen Toma; Kevin Jon Williams; Jeff M Venstrom; Brian M Alexander; Nikunj Shah; Natalie Danziger; Amanda C Hemmerich; Eric A Severson; Jonathan Keith Killian; Douglas I Lin; Jeffrey S Ross; Julie Y Tse; Shakti H Ramkissoon; Mark C Mochel; Julia A Elvin Journal: JCO Precis Oncol Date: 2020-06-16