Human papilloma virus (HPV) infection is implicated in a proportion of invasive squamous cell carcinoma of the penis (PC). A subset of PC involves dysregulation of the p53 pathway. HPV in situ hybridization (ISH) and p16ink4a positivity are surrogate markers for HPV infection, and p53 immunohistochemistry (IHC) denotes abnormality in the p53 pathway. There remains an ambiguity with regard to the contribution of both the pathways in the prognosis of PC. We sought to analyze the clinicopathologic characteristics of a cohort of Indian PC patients with respect to p16 ink4a and p53 expression.
A cohort of 123 PC patients was studied for p16ink4aand p53IHC and HPVISH. The results of these biomarkers were correlated with various clinicopathologic parameters.
p16ink4a and HPV ISH were positive in 47% and 53% of the tumors, respectively. The proportion of warty, basaloid, or mixed warty-basaloid tumor subtypes showed significant p16ink4apositivity (P < .0001) compared to other subtypes. Twenty-eight patients were dual negative (p53- /p16ink4a-), 32 were dual positive (p53+/p16ink4a+), 38 were p53+/p16ink4a-, and 25 were p53-/p16ink4a +. In patients where p16ink4a was negative, a p53-positive phenotype had a higher propensity for lymph node metastases (OR, 5.42; 95% CI, 1.75-16.80; P = .003). Similarly, p53 positivity dictates nodal involvement in the p16ink4a-positive subset of tumors (OR, 5.00; 95% CI, 1.23-20.17; P = .024). On multivariate analyses, pathologic subtypes (warty, warty-basaloid, and basaloid) (P < .0001), p16ink4aexpression (P < .0001), and absence of nodal metastasis (P < .0001) were significant predictors of improved overall (OS) and cancer specific survival (CSS). In Kaplan-Meier analysis, the OS was significantly longer in patients with p16ink4a + tumors (P < .0001), as was the CSS (P < .0001). Patients with dual positive tumors had a significantly higher OS (P < .001) and CSS (P = .012), in the entire cohort. In the node positive patients, dual positivity was associated with significantly higher OS (P < .0001); however, the median CSS for p53+/p16ink4a+tumors were not significantly different compared to p53- /p16ink4a- tumors (P = .064), although there was a trend towards improved CSS.
There is a strong concordance between p16ink4aIHC and HPV ISH results. p16ink4a status is an independent predictor of survival (OS and CSS) in our cohort of PCs. p53 is a predictor of nodal metastasis irrespective of p16 status. Dual positive tumors have a significantly better outcome in comparison to dual negative tumors.
Clinical genitourinary cancer. 2021 Jul 10 [Epub ahead of print]
Sambit K Mohanty, Sourav K Mishra, Nitin Bhardwaj, Ruhani Sardana, Sunil Jaiswal, Niharika Pattnaik, Dinesh Pradhan, Shivani Sharma, Seema Kaushal, Manas R Baisakh, Suren Das, Manas R Pradhan, Kaliprasad Satapathy, Ashis Pattnaik, Shailendra K Sharma, Chira R Khadenga, Subodh Das, Debadarshi Rath, Biswajit Nanda, Anil V Parwani
Department of Pathology and Laboratory Medicine, Advanced Medical Research Institute, Bhubaneswar, India; Department of Pathology and Laboratory Medicine, CORE Diagnostics, Gurgaon, India., Department of Medical Oncology, Advanced Medical Research Institute, Bhubaneswar, India., Department of Pathology and Laboratory Medicine, CORE Diagnostics, Gurgaon, India., Department of Pathology and Laboratory Medicine, Advanced Medical Research Institute, Bhubaneswar, India., Department of Surgical Oncology, Advanced Medical Research Institute, Bhubaneswar, India., Aurora Diagnostics, Jacksonville, FL., Department of Pathology, All India Institute of Medical Sciences, New Delhi, India., Department of Pathology and Laboratory Medicine, Prolife Diagnostics, Bhubaneswar, India., Department of Urology, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India., Department of Urology, Advanced Medical Research Institute, Bhubaneswar, India., Department of Urology, Kalinga Hospital, Bhubaneswar, India., Department of Radiation Oncology, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India., Department of Pathology, Wexner Medical Center, Columbus, OH. Electronic address: .