The Biomarker Potential of Caveolin-1 in Penile Cancer

Abstract

Various types of human cancers were characterized by an altered expression of epithelial or stromal caveolin-1 (CAV1). However, the clinical significance of CAV1 expression in penile cancer remains largely unknown. Here the expression patterns of CAV1 were analyzed in a retrospective cohort (n=43) of penile squamous cell carcinomas (SCC). Upon penile cancer progression, significantly increased CAV1-levels were determined within the malignant epithelium, whereas within the tumor stroma, namely the fibroblastic tumor compartment harboring activated and/or cancer associated fibroblasts, CAV1 levels significantly decline. Concerning the clinicopathological significance of CAV1 expression in penile cancer as well as respective epithelial-stromal CAV1 distributions, high expression within the tumor cells as well as low expression of CAV1 within the stromal compartment were correlated with decreased overall survival of penile cancer patients. Herein, CAV1 expressions and distributions at advanced penile cancer stages were independent of the immunohistochemically proven tumor protein p53 status. In contrast, less differentiated p16-positive tumor epithelia (indicative for human papilloma virus infection) were characterized by significantly decreased CAV1 levels. Conclusively, we provide further and new evidence that the characteristic shift in stromal‐epithelial CAV1 being functionally relevant to tumor progression even occurs in penile SCC.

Current State of Cell Therapies for Genitourinary Malignancies

“…Penile cancer is a rare, but aggressive cancer that disproportionally affects men in Africa, Asia, and South America 67,68 . Most penile cancers are squamous cell carcinomas, and risk factors include smoking and human papillomavirus (HPV) exposure, with approximately 50% of penile cancers being HPV + 69,70 . At the early stage of disease presentation, patients with penile cancer are treated with topical agents or surgical resection of local lesions.…”

“…67,68 Most penile cancers are squamous cell carcinomas, and risk factors include smoking and human papillomavirus (HPV) exposure, with approximately 50% of penile cancers being HPV + . 69,70 At the early stage of disease presentation, patients with penile cancer are treated with topical agents or surgical resection of local lesions. Patients with lymph node metastasis have a significantly worse prognosis and are treated with a lymph node surgical resection and systemic chemotherapy.…”

Tumor Location May Independently Predict Survival in Patients With M0 Squamous Cell Carcinoma of the Penis

“…Several biomarkers for SCCP have been identified, although they are not routinely available in diagnosis and treatment. Panic et al demonstrated that the characteristic shift in stromalepithelial caveolin-1 (CAV1) was correlated with tumor progression in SCCP (14). Hu et al found that overexpression of inhibitor of DNA binding 1 (ID1) was significantly relevant to lymph node metastasis in SCCP (15).…”

“…Panic et al. demonstrated that the characteristic shift in stromal-epithelial caveolin-1 (CAV1) was correlated with tumor progression in SCCP ( 14 ). Hu et al.…”

miR-138-5p-mediated HOXD11 promotes cell invasion and metastasis by activating the FN1/MMP2/MMP9 pathway and predicts poor prognosis in penile squamous cell carcinoma

“…The detailed mechanisms behind tumor progression remain elusive. Although a recent genetic understanding of PSCC has shown that HRAS mutations, EGFR ampli cations, and dysregulation of CAV1 and IDO1 are associated with advanced disease [10][11][12], most studies lack speci c mechanisms owing to the lack of appropriate PSCC cell lines, convincing metastatic experiments in vivo and large-scale clinical validations. Our previous studies have established a molecular strati cation to predict high-risk PSCC patients with lymph node metastasis [13,14], but the mechanism needs to be further explored in depth.…”