EGFR Mutation Is Specific for Terminal Respiratory Unit Type Adenocarcinoma

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Abstract
We have previously reported that terminal-respiratory-unit (TRU) type adenocarcinoma is a distinct subset of lung adenocarcinoma in terms of molecular pathway for carcinogenesis and phenotypic profiles. This type of cancer shows TRU features, characterized by distinct cellular morphology and the expression of TTF-1 and surfactant proteins. Recently, two groups published novel mutations of the epidermal growth factor receptor (EGFR) that are closely associated with clinical response to gefitinib. The clinicopathologic features of gefitinib responders overlap with those of TRU-type adenocarcinoma, and the characteristics of TRU are likely to correspond to the bronchioloalveolar features reported as a predictor of gefitinib response. We therefore examined the characteristics of EGFR-mutated pulmonary adenocarcinomas with special reference to TRU-type adenocarcinoma. EGFR mutation was detected in 97 of 195 adenocarcinomas, 91 of 149 TRU-type adenocarcinomas and 6 of 46 tumors of other types. Conversely, 91 of 97 EGFR-mutated adenocarcinomas were categorized as TRU-type adenocarcinomas. This type-specific involvement was confirmed by logistic regression model. In addition, EGFR mutation was detected in some cases of atypical adenomatous hyperplasia, a preinvasive lesion of TRU-type adenocarcinoma. These findings further confirm that TRU-type-adenocarcinoma is a distinct adenocarcinoma subset in which a particular molecular pathway is involved.