Significance of the epidermal growth factor receptor mutation status and differences among molecular subgroups in surgically resected lung microinvasive adenocarcinoma

Abstract

Lung microinvasive adenocarcinoma (MIA) is a newly-defined subtype of early stage non-small cell lung cancer (NSCLC). However, its epidermal growth factor receptor (EGFR) mutation status and clinical significance remain unclear. The present study aimed to determine EGFR mutation characteristics and identify their significance in patients with resected lung MIA. The present study also analyzed clinicopathological differences between EGFR molecular subgroups defined as 19Del and L858R. The present study examined EGFR mutations in 79 consecutive lung MIA resection specimens and compared the differences in clinicopathological features between the EGFR wild-type and mutation groups, as well as between the 19Del and L858R subgroups. EGFR mutations were detected in 60 (75.95%) tumors. The most common mutations were 19Del (28 cases; 35.44%) and L858R (30 cases; 37.97%). Two patients harbored rare mutations and one of them had a concomitant double mutation. EGFR mutations were significantly associated with microinvasion component, thyroid transcription factor 1 (TTF-1) expression, intratumoral fibrosis and inflammatory cell infiltration. Subgroup evaluation indicated that there was a significant association between 19Del and tumor size, maximum diameter of microinvasion, presence of intratumoral fibrosis and inflammatory cell infiltration. Similar associations were observed for the L858R subgroup, and L858R was associated with TTF-1 expression. In particular, 19Del occurred more frequently in MIA with a smaller size, with a smaller microinvasive area, without TTF-1 expression, and lacking intratumoral fibrosis and inflammatory cell infiltration. By contrast, L858R was detected more frequently in MIA with entirely different tumor features. In conclusion, the results of the present study indicated that surgically resected MIA cases harboring different EGFR gene statuses exhibit distinct clinicopathological features. Significant differences in pathological features associated with the tumor microenvironment were identified in MIA with 19Del or L858R mutations. Therefore, the present study proposed that MIA should be classified into molecular subgroups based on EGFR mutation subtypes. The molecular sub-classification should be taken into account for prognostic evaluation and clinical management of MIA.