Penile squamous cell carcinoma (pSCC) is a rare genitourinary tumor associated with notable psychosexual distress and poor prognosis. Traditional prognostic factors for pSCC include TNM stage and histological grade, with lymph node metastases being a critical indicator of poor prognosis. This study aimed to evaluate the prognostic impact of the following immunohistochemistry markers routinely used in histopathology practice: GATA3, IMP3, HIF-1-α, CK7, CA-IX, HER2, and TTF-1. A retrospective cohort of 145 patients with pSCC was analyzed using tissue microarray and immunohistochemical techniques. Overall survival (OS) was correlated statistically with detected marker expression. Key findings include that low GATA3 expression is associated with significantly worse OS in univariate Cox regression truncated at 3 years of follow-up. Low GATA3 retained prognostic impact when adjusted for major clinicopathological variables: Age, pT and pN stage, grade, lymphatic, venous, and perineural invasion, lymphocytic infiltrate, and expression of p16, p53, and PD-L1. Low GATA3 expression was associated with shorter cancer-specific survival (CSS) at 10 years follow-up. IMP3, CK7, and CA-IX showed statistically insignificant trends towards poorer prognosis. CK7 and CA-IX were more frequently expressed in high grade pSCC and in p16/HPV-positive tumors. IMP3 and CA-IX were associated with regional lymph node metastases. All cases were negative in TTF-1 and HER2. This study suggests GATA3 as a potential prognostic marker in pSCC.

Department of Anaesthesia and Intensive Care Medicine 3rd Faculty of Medicine Charles University University Hospital Kralovske Vinohrady Šrobárova 1150 50 100 34 Prague Czech Republic

Department of Pathology 1st Faculty of Medicine Charles University General University Hospital Studničkova 2 128 00 Prague Czech Republic

Department of Pathology 3rd Faculty of Medicine Charles University University Hospital Kralovske Vinohrady Šrobárova 1150 50 100 34 Prague Czech Republic

Department of Pathology and Molecular Medicine 3rd Faculty of Medicine Charles University Thomayer University Hospital Vídeňská 800 140 59 Prague Czech Republic

Department of Urology 3rd Faculty of Medicine Charles University University Hospital Kralovske Vinohrady Šrobárova 1150 50 100 34 Prague Czech Republic

Department of Urology 3rd Faculty of Medicine of Charles University Thomayer University Hospital Vídeňská 800 100 34 Prague Czech Republic

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