Análise da expressão de ALK, P16, PD-1 E PD-L1 por imunoistoquímica em amostras teciduais de câncer de pênis

Abstract

Penile carcinoma (PC) is a rare cancer in developed countries, but endemic in several regions of the world, with the most common histologic type being squamous cell carcinoma (SCC). The incidence of penile cancer is associated with several factors, with room for primary preventive measures. In addition, correct diagnosis and treatment can lead to cure in most cases. The anaplastic lymphoma protein kinase (ALK) is a member of the super tyrosine kinase receptor family of insulin, which also includes other cancer-relevant tyrosine kinases, this protein has been associated with clinical and pathological characteristics of patients with non-small cell lung cancer (NSCLC) for undergoing gene rearrangements. Crizotinib, the first developed human ALK inhibitor, is a drug whose main activity is to suppress the proliferation of anaplastic cells with ALK activation. Patients with NSCLC and positive ALK when treated with Crizotinib had excellent survival results. The tumor suppressor protein P16 acts to control cell proliferation in response to human papilloma virus (HPV) infection. More recently, it has been used as a high-risk HPV surrogate marker for cervical cancer and in head and neck tumors. Immunotherapy has received great attention and the development of drugs that block the binding of programmed cell death receptor-1 (PD-1) with the programmed cell death ligand-1 (PD-L1), to restore immune system function and induce an anticancer immune response. These PD-1 and PD-L1 biomarkers may be overexpressed and may be a negative or positive prognostic factor, depending on cancer. Several methods have been used to evaluate the presence of ALK rearrangements, and the expressions of P16, PD-1 and PD-L1. This study aimed to identify and analyze the expression of proteins ALK (D5F3), P16 (E6H4), PD-L1 and PD-1 in tumor tissue samples from patients with penile carcinoma by immunohistochemistry, and to verify if there is any relationship between the expression of these proteins and various demographic, clinical and pathological factors used as prognostic and disease staging, such as histological subtype, histological grade, pathological extension, lymph node status, and survival, among others. The study of the correlation between P16 and HPV and the possibility of using Crizotinib in patients with ALK-positive penile carcinoma, both represent a possible innovative contribution to the treatment of this disease, as well as the application of immunotherapy for PD-1 and PD-L1 positive patients. Expression of P16 (E6H4) and PD-L1 was detected, however, there was no expression of ALK (D5F3) and PD-1. P16 expression was directly correlated with tumor grade, lymph node classification and histological status. Tumor grade, lymphatic vascular invasion and lymph node staging were also directly related to PD-L1 expression. The presence of HPV was related to tumor grade and perineural invasion.