Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas with Adverse Prognosis

Isabel Trias
,
Ferran Algaba
,
Inés De Torres
ORCID logo ,
Adela Saco
,
Lorena Marimon
ORCID logo ,
Núria Peñuelas
,
Laia Diez-Ahijado
,
Lia Sisuashvili
,
Katarzyna Darecka
,
Alba Morató
,
Marta Del Pino
ORCID logo ,
Carla Ferrandiz-Pulido
,
Maria J. Ribal
,
Tarek Ajami
,
Juan Manuel Corral Molina
ORCID logo ,
Josep M. Gaya
,
Oscar Reig
,
Oriol Ordi
,
Inmaculada Ribera-Cortada
,
Adriana García-Herrera
,
Natalia Rakislova
* ORCID logo
Version 1 : Received: 15 March 2024 / Approved: 18 March 2024 / Online: 18 March 2024 (09:42:24 CET)

How to cite: Trias, I.; Algaba, F.; De Torres, I.; Saco, A.; Marimon, L.; Peñuelas, N.; Diez-Ahijado, L.; Sisuashvili, L.; Darecka, K.; Morató, A.; Del Pino, M.; Ferrandiz-Pulido, C.; Ribal, M.J.; Ajami, T.; Molina, J.M.C.; Gaya, J.M.; Reig, O.; Ordi, O.; Ribera-Cortada, I.; García-Herrera, A.; Rakislova, N. p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas with Adverse Prognosis. Preprints 2024, 2024030996. https://doi.org/10.20944/preprints202403.0996.v1 Trias, I.; Algaba, F.; De Torres, I.; Saco, A.; Marimon, L.; Peñuelas, N.; Diez-Ahijado, L.; Sisuashvili, L.; Darecka, K.; Morató, A.; Del Pino, M.; Ferrandiz-Pulido, C.; Ribal, M.J.; Ajami, T.; Molina, J.M.C.; Gaya, J.M.; Reig, O.; Ordi, O.; Ribera-Cortada, I.; García-Herrera, A.; Rakislova, N. p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas with Adverse Prognosis. Preprints 2024, 2024030996. https://doi.org/10.20944/preprints202403.0996.v1

Abstract

Background: Penile squamous cell carcinoma (PSCC) is classified into two prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. Conversely, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with prognosis in a large series of PSCC patients. p53 was analysed according to a recently described immunohistochemical (IHC) pattern-based framework that includes two normal (scattered, mid-epithelial) and four abnormal patterns (diffuse, basal overexpression, cytoplasmic and null) and closely correlates with TP53 mutational status. Methods: A total of 122 patients with surgically treated PSCC in three hospitals in Barcelona, Spain, were included. Based on HPV in situ hybridization and p16 and p53 IHC expression, the tumors were classified into three molecular types: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed for at least 22 months (median 56.9 months), and disease-specific survival (DSS) was analysed. Results: 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 patterns not recognized in the classical p53 IHC interpretation (basal, null, cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired DSS (hazard ratio=23.4, 95% confidence interval [CI]= 2.7-3095.3; p=0.001 and 16.3, 95% CI=1.8-2151.5; p=0.008, respectively). 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 two prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

Keywords

penile cancer; penile squamous cell carcinoma; HPV; p53; prognosis; disease-specific survival

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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