Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF

Abstract

Squamous cell carcinoma of the penis (SSCP) represents 95% of penile cancers. It affects mostly uncircumcised patients and is often associated with lack of adequate local hygiene and phimosis. In Brazil, the incidence is 2.7% but in some areas of the country can reach 17% of diagnosed cases of cancer per year. The tumor can occur in any part of the sexual organ and the type of staging to be used is controversial. The Broders classification is more often used to classify tumors. Studies suggest the relationship between the development of penile carcinoma and HPV infection (Human Papilloma Virus). The evaluation method of inguinal lymph nodes remains controversial and it is difficult to differentiate inflammatory reaction from metastatic lymphadenopathy. Physical examination is not a reliable predictor of lymph node involvement since patients with palpable lymph nodes can not present metastases. There are few publications about the molecular mechanisms involved in the genesis and progression of the SSCP. Although several markers have been evaluated, currently the clinical application of these is limited. Most of the markers studied require invasive procedures for obtaining tumor tissue. There is a need to find through a minimally invasive technique circulating tumor markers able to differentiate SSCP patients with and without metastatic involvement. In this type ofmalignancythediscovery of biomarkers that assessthe prognosisis relevant since physical examination is not a reliable predictor oflymph node involvementand survival. The objectives of this study were: 1) to review and discuss the epidemiology, etiology, different types of surgical approach and controversies in the surgical treatment of penile cancer 2)to investigate via the platform ClinProt / MALDI / TOF presence of plasma markers able to discriminate healthy subjects from patients affected by squamous cell carcinoma of the penis (SCCP) 3) to evaluate the importance of these markers in disease progression. Between June 2010 and June 2011, plasma samples from 36 healthy subjects and 25 patients with penile carcinoma who underwent surgical treatment in the UrologyServicesofNational Cancer InstituteandMarioKröeffHospital were collected and analyzed by the ClinProt/MALDI/TOF platform. Our results found a cluster of 2 peptides (A=m/z 1897.22 +-9 Da and B=m/z 2021.99 +-9 Da that was able to discriminate patients from controls subjects. These peptides were further identified as C3 and C4 A/B fragments from complement system. Cross validation analysis using the whole casuistic showed 62.5% and 86.76% of sensitivity and specificity, respectively with a very high sensitivity (100%) and specificity (97%) for SCCP patients that have died by disease. Moreover, patients with lymph node involvement present a sensitivity and specificity of 80% and 97%, respectively. The results showed that as the disease progresses more under express are the cluster comparing with healthy subjects. These results may be useful as prognostic toll.