Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based framework that includes 2 normal and 4 abnormal patterns and closely correlates with TP53 mutational status. A total of 122 patients with surgically treated PSCC in 3 hospitals were included. Based on HPV in situ hybridization and p16 and p53 IHC, the tumors were classified into 3 subtypes: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed up for at least 22 months (median: 56.9 months). Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (P< 0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 abnormal patterns not recognized in the classic p53 IHC interpretation (basal, null, and cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired disease-specific survival (hazard ratio = 23.4, 95% CI = 2.7-3095.3; P= 0.001 and 16.3, 95% CI = 1.8-2151.5; P= 0.008, respectively). In conclusion, compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define 2 prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.
The American journal of surgical pathology. 2024 Jul 23 [Epub ahead of print]
Isabel Trias, Ferran Algaba, Inés de Torres, Adela Saco, Lorena Marimon, Núria Peñuelas, Laia Diez-Ahijado, Lia Sisuashvili, Katarzyna Darecka, Alba Morató, Marta Del Pino, Carla Ferrándiz-Pulido, María José Ribal, Tarek Ajami, Juan Manuel Corral, Josep Maria Gaya, Oscar Reig, Oriol Ordi, Inmaculada Ribera-Cortada, Adriana García-Herrera, Natalia Rakislova
Department of Pathology, Hospital Clinic of Barcelona-University of Barcelona, Barcelona, Spain., Department of Pathology, Fundació Puigvert-Universitat Autònoma de Barcelona, Barcelona, Spain., Department of Pathology, Hospital Universitari Vall d'Hebron-Universitat Autònoma de Barcelona, Barcelona, Spain., Barcelona Institute for Global Health (ISGlobal)-University of Barcelona, Barcelona, Spain., Medicine and Health Sciences Faculty (Facultat de Medicina i Ciències de la Salut)-University of Barcelona, Barcelona, Spain., Department of Dermatology, Hospital Universitari Vall d'Hebron-Universitat Autònoma de Barcelona., Uro-Oncology Unit, Hospital Clínic de Barcelona-University of Barcelona., Department of Urology, Fundació Puigvert-Universitat Autònoma de Barcelona, Barcelona, Spain., Translational Genomic and Targeted Therapeutics in Solid Tumors, Oncology and Haematology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.