Dados do Trabalho

Título

MYC COPY NUMBER ALTERATIONS IN PENILE SQUAMOUS CELL CARCINOMA

Introdução e Objetivo

Penile Squamous Cell Carcinoma (PSCC) is a rare malignancy; however, the incidence is higher in developing countries. In Brazil, the state of Maranhão is assumed to be the highest reported incidence of PSCC worldwide.The MYC gene locus is described as a significant site of HPV integration, leading to gene overexpression and carcinogenesis, since is involved in many mechanisms of cell's expression. The present study aimed to analyze the copy number alterations (CNA) and protein expression of MYC in 40 PSCC samples, collected from patients treated at three referral hospitals in Maranhão, Brazil.

Método

Tumor DNA was extracted and HPV detection was carried out using the nested-PCR (PGMY09/11 and GP5+/6+). Copy number (CN) analysis was performed by qPCR using TaqMan copy number assays for MYC. CN analysis results were defined as gain (3 copies) and amplification (≥ 4 copies). The MYC protein expression assay was performed by immunohistochemistry (IHC) using the monoclonal anti-myc antibody (clone EP121). Staining in ≥ 40% of invasive PSCC was considered positive (overexpression). Categorical variables were analyzed using chi-square or fisher's exact tests.

Resultados

The patients had a mean age of 59.6 ± 15.0 years, a low level of education (77.5%), were alcohol consumers (75.0%), smokers (45.0%), and exhibited phimosis (55.0%). The lesions were predominantly located on the penile glans (52.5%) with sizes ranging from 2.1 to 5.0 cm (57.5%). Histologically, the majority of tumors were usual (52.5%), poorly differentiated (75.0%), with the presence of koilocytosis (65.0%), at pT3/pT4 stage (50.0%), stage II (62.5%), and exhibited metastasis (50.0%). Angiolymphatic invasion and perineural invasion were observed in 37.5% and 50.0% of cases, respectively. The presence of HPV was detected in 55.0% of the cases. IHC results showed positivity in 52.5% of cases. MYC gain and amplification were identified in 37.5% and 10% of PSCC samples, respectively. MYC overexpression was statistically significant for HPV infection (P=0.028). Pathological stage (P=0.027) and koilocytosis (P=0.049) were positively associated with CN alterations. Interestingly, HPV was detected more frequently in samples without CN alterations (P=0.007).

Conclusão

In this study, we observed an increased MYC overexpression in HPV-positive samples. However, it may not be directly associated with HPV integration in the MYC locus or MYC gains/amplifications. Therefore, our study group is currently conducting RT-qPCR assays and HPV genotyping to elucidate this association.