Evaluation of the frequency of EGFR, KRAS and EML4-ALK mutation in adenocarcinomas and their subtypes and impact of expression of hyaluronidases and hyaluronic acid synthase in pre-neoplastic lung lesions

Abstract

Adenocarcinomas represent the most common histologic subtype in most countries, contributing to almost half of cases of lung cancer. How huge sources have been spent on trials involving therapeutic aspects in adenocarcinomas, there is need to develop standard criteria to improve behavior, therapy and prognosis of patients. Important changes begin to occur in the treatment of metastatic disease, especially in relation to specific molecular alterations, such as the EGFR mutation, KRAS, and EML4-ALK translocation. Example that includes this kind of progress comes from the use of oral tyrosine kinase inhibitors of EGFR such as gefitinib and erlotinib. In 1999 and 2004, WHO recognized the atypical adenomatous hyperplasia (AAH) as a pre-invasive lesion for adenocarcinoma of the lung, since these lesions are incidental findings ffi the adjacent lung parenchyma in 5 to 23% of resected lung adenocarcinomas. Earty detection of precancerous lesions in individuals at risk, could curb the neoplastic transformation and especially metastases. Quantitative and qualitative changes in hyaluronidase (Hyalos) and Hyaluronic Acid Synthases (HAS), can cause degradation of the extracellular matrix and promote tumor growth and invasion. In this project, we intend to continue our line of research, evaluating the Hyall by immunohistochemistry and 3 and HAS 1, 2 and 3 in pre-neoplastic lung lesion and enjoy the series we already have to assess the frequency of mutation of KRAS and EGFR markers by PCR and EML4-ALK by FISH in three reference centers in the country. Knowledge of the frequency of mutation of EGFR, KRAS and EML4-ALK fusion and genetic profile of patients in three major centers of references can be expanded to the rest the country, allowing a personalized therapy directed at our regional variations. (AU)