Dlaždicobuněčný karcinom penisu -- etiologie, imunitní mikroprostředí a nové prognostické markery.

Penile cancer is a relatively rare malignancy with a highly variable prognosis. The most important indicator of cancer specific survival (CSS) is the involvement of regional lymph nodes, which may not be identified during clinical examination or by conventional imaging methods. For that reason, new prognostic and therapeutic markers of penile squamous cell carcinoma (SCC) are currently being investigated at the histological, immunohistochemical and molecular level. Although the WHO classifies penile SCC into HPV-associated and HPV-independent, the prognostic impact of HPV status remains questionable according to several studies and our data. In our study, a negative prognostic effect of tumour grade budding on overall survival (OS) and CSS was found. Tumour budding has been associated with the metastatic involvement of regional lymph nodes in penile SCC. A few relevant studies have investigated the prognostic significance of immune cell infiltration in pSCC. In our study, a non-brisk/absent lymphocyte infiltrate was significantly associated with shorter OS and CSS. Mutated p53 profile correlates with aggressive phenotype and poor prognosis in many tumour types including penile SCC. Our data confirmed its negative prognostic impact on both OS and CSS. High tumour mutational burden (TMB) was associated with shorter OS, with high programmed death ligand 1 (PD-L1) expression and HPV/p16 negativity. The PD-L1 positivity enrichment in HPV-negative tumours harboring high TMB illustrates pSCC oncogenesis in association with chronic inflammation, high amount of acquired mutations, and neoantigen (PD-L1) production. This discovery suggests that patients with HPV-independent SCC could be suitable candidates for anti-PD-1/PD-L1 treatment. In summary, tumour budding, tumour lymphocytic infiltration and p53 show a stronger correlation with survival outcomes compared to factors such as pT stage, histopathological grade or morphological subtype in penile carcinoma. [ABSTRACT FROM AUTHOR]