The clinicopathological significance of ALK rearrangements and KRAS and EGFR mutations in primary pulmonary mucinous adenocarcinoma.

Abstract

Primary pulmonary mucinous adenocarcinoma (PPMA) is one of the important subtypes of lung adenocarcinoma. Detection of anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements and of KRAS and epidermal growth factor receptor (EGFR) mutations will help in diagnosing and predicting treatment outcome. The aim of this study was to investigate the clinicopathological significance of ALK rearrangements, KRAS and EGFR mutations in PPMA. ALK expression was detected immunohistochemically. KRAS and EGFR mutations were determined by the amplification refractory mutation system. Seventy-three patients of PPMA were enrolled. ALK rearrangements were detected in 34.2 % of patients and were more frequent in upper/middle lobe, stage III-IV, lymphatic permeation-positive patients and non-smokers. ALK rearrangements were significantly increased in the solid tumor predominant with mucin production subtype, and in special tissue structures, including signet ring cells, cribriform, and micropapillary patterns. KRAS mutations were observed in 23.3 % of patients and were more prevalent in invasive mucinous adenocarcinoma and lower lobe tumors. Only one case of ALK rearrangements harbored KRAS mutation, and no cases manifested with the coexistence of ALK rearrangements and EGFR mutations. KRAS and EGFR co-mutation was detected in one case. PPMA patients with ALK rearrangements or KRAS mutation represent a unique subtype in NSCLC. The results provide basis data for target therapy screening of PPMA patients.