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. 2025 Jul;40(7):1013-1039.
doi: 10.14670/HH-18-846. Epub 2024 Nov 7.

Identification of new tissue markers for the monitoring and standardization of penile cancer according to the degree of differentiation

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Identification of new tissue markers for the monitoring and standardization of penile cancer according to the degree of differentiation

Carlos Casanova-Martín et al. Histol Histopathol. 2025 Jul.

Abstract

Penile cancer is an uncommon disease compared with other urological tumors and is more common in low- and middle-income countries. Risk factors include age, ethnicity, smoking, hygiene, and human papillomavirus infection. Although carcinoma of the penis can be cured in up to 80% of cases if detected early, late diagnosis drastically reduces survival rates, especially in metastatic cases. More than 95% of cases are squamous cell carcinomas, and the degree of cell differentiation is a key histopathological factor, distinguishing between poorly (P), moderately (M), and well-differentiated (W) carcinomas, with verrucous carcinoma (V) having the best prognosis due to its low metastatic capacity. This study analyses the differential expression of several biomarkers related to cell proliferation and cell cycle, inflammation, epigenetics, and autophagy (cell cycle (IRS-4, Ki-67, RB1, CDK4, cyclin D1, ERBB2, β-catenin, and MAGE-A), inflammation (COX2, NLRP3, and AIF-1), epigenetics (HAT-1) and autophagy (ULK-1 and ATG9A) in penile carcinoma according to the degree of differentiation. Immunohistochemical techniques were performed on 34 penile squamous cell carcinoma (PSCC) samples classified into subtype V (N=6), and groups P (N=9), M (N=9), and W (N=10). The findings suggest a differential expression of molecules according to the degree of cell differentiation, with a higher differential expression of molecules according to the degree of cell differentiation, suggesting that the proteins studied could have predictive value. The study highlights the complexity of PSCC and the need for future studies to explore translational applications and search for new biomarkers to improve clinical management and understanding of this disease.

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