1. 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
- Author
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Linn Woelber, Sven Mahner, Peer Hantschmann, Sophie Fuerst, Ulrich Canzler, Eike Burandt, Werner Meier, Matthias W. Beckmann, Alexander Mustea, Dirk Bauerschlag, R Klapdor, I Braicu, Georg Schmidt, Matthias Kalder, Christine Eulenburg, Leticia Oliveira-Ferrer, Julia Kathrin Jueckstock, Nikolaus de Gregorio, Martin Heubner, Martin Hellriegel, Karl Ulrich Petry, Maximilian Klar, Atanas Ignatov, Stefan Kommoss, Hans-Georg Strauss, and Katharina Prieske
- Subjects
p53 ,Oncology ,Vulvar Squamous Cell Carcinoma ,medicine.medical_treatment ,Medizin ,p16 ,Lichen sclerosus ,medicine.disease_cause ,Translational Research, Biomedical ,0302 clinical medicine ,Germany ,030212 general & internal medicine ,Stage (cooking) ,vulvar cancer ,030219 obstetrics & reproductive medicine ,Tissue microarray ,Vulvar Neoplasms ,Obstetrics and Gynecology ,Middle Aged ,Immunohistochemistry ,Up-Regulation ,3. Good health ,Phenotype ,Carcinoma, Squamous Cell ,Female ,Adult ,HPV ,medicine.medical_specialty ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,Retrospective Studies ,business.industry ,Papillomavirus Infections ,Vulvar cancer ,medicine.disease ,Survival Analysis ,Radiation therapy ,Tissue Array Analysis ,Mutation ,prognosis ,Tumor Suppressor Protein p53 ,business ,Carcinogenesis ,Follow-Up Studies - Abstract
Background: There are 2 known pathways for tumorigenesis of vulvar squamous cell carcinoma—a human papillomavirus–dependent pathway characterized by p16 overexpression and a human papillomavirus–independent pathway linked to lichen sclerosus, characterized by TP53 mutation. A correlation of human papillomavirus dependency with a favorable prognosis has been proposed.Objective: The objective of the study was to further understand the role of human papillomavirus and p53 status in vulvar squamous cell carcinoma and characterize its clinical relevance.Study Design: The Arbeitsgemeinschaft Gynaecological Oncology Chemo and Radiotherapy in Epithelial Vulvar Cancer-1 study is a retrospective cohort study of 1618 patients with primary vulvar squamous cell carcinoma Fédération Internationale de Gynécologie et d'Obstétrique stage ≥1B treated at 29 gynecologic cancer centers in Germany between 1998 and 2008. For this translational substudy, formalin-fixed paraffin-embedded tissue was collected. A tissue microarray was constructed (n=652 samples); p16 and p53 expression was determined by immunohistochemistry. Human papillomavirus status and subtype were analyzed by polymerase chain reaction.Results: p16 immunohistochemistry was positive in 166 of 550 tumors (30.2%); p53 staining in 187 of 597 tumors (31.3%). Only tumors with available information regarding p16 and p53 immunohistochemistry and without p53 silent expression pattern were further analyzed (n=411); 3 groups were defined: p53+ (n=163), p16+/p53− (n=132), and p16−/p53− (n=116). Human papillomavirus DNA was detected in 85.6% of p16+/p53− tumors; human papillomavirus-16 was the most common subtype (86.3%). Patients with p16+ tumors were younger (64 vs 72 years for p53+, respectively, 69 years for p16−/p53− tumors; PConclusion: p16 overexpression is associated with an improved prognosis whereas p53 positivity is linked to an adverse outcome. Our data support the hypothesis of a clinically relevant third subgroup of vulvar squamous cell carcinoma with a p53−/p16− phenotype showing an intermediate prognosis that needs to be further characterized.
- Published
- 2021
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