p53 and p16 expression profiles in vulvar cancer: a translational analysis by the Arbeitsgemeinschaft Gynäkologische Onkologie Chemo and Radiotherapy in Epithelial Vulvar Cancer study group

Background There are 2 known pathways for tumorigenesis of vulvar squamous cell carcinoma—a human papillomavirus–dependent pathway characterized by p16 overexpression and a papillomavirus–independent linked to lichen sclerosus, TP53 mutation. A correlation papillomavirus dependency with favorable prognosis has been proposed. Objective The objective the study was further understand role p53 status in carcinoma characterize its clinical relevance. Study Design Arbeitsgemeinschaft Gynaecological Oncology Chemo Radiotherapy Epithelial Vulvar Cancer-1 is retrospective cohort 1618 patients primary Fédération Internationale de Gynécologie et d'Obstétrique stage ≥1B treated at 29 gynecologic cancer centers Germany between 1998 2008. For this translational substudy, formalin-fixed paraffin-embedded tissue collected. microarray constructed (n=652 samples); expression determined immunohistochemistry. Human subtype were analyzed polymerase chain reaction. Results immunohistochemistry positive 166 550 tumors (30.2%); staining 187 597 (31.3%). Only available information regarding without silent pattern (n=411); 3 groups defined: p53+ (n=163), p16+/p53− (n=132), p16−/p53− (n=116). DNA detected 85.6% tumors; papillomavirus-16 most common (86.3%). Patients p16+ younger (64 vs 72 years p53+, respectively, 69 P<.0001) showed lower rates lymph-node involvement (28.0% 42.3% 30.2% P=.050). Notably, 2-year-disease-free overall survival significantly different among groups: disease-free survival, 47.1% (p53+), 60.2% (p16−/p53−), 63.9% (p16+/p53−) (P<.001); 70.4% 75.4% 82.5% (P=.002). In multivariate analysis, phenotype consistently improved compared other (hazard ratio, 0.66; 95% confidence interval, 0.44–0.99; P=.042). Conclusion associated an whereas positivity adverse outcome. Our data support hypothesis clinically relevant third subgroup p53−/p16− showing intermediate that needs be characterized.