Clinicopathological features of younger (aged ≤ 50 years) lung adenocarcinoma patients harboring the EML4-ALK fusion gene

Abstract

Background: The EML4-ALK fusion gene has recently been identified as a driver mutation in a subset of non-small cell lung cancers. In subsequent studies, EML4-ALK has been detected in a low percentage of patients, and was associated with a lack of EGFR or KRAS mutations, younger age, and adenocarcinoma with acinar histology. Cases with the EML4-ALK fusion gene were examined to clarify the clinicopathological characteristics of young adenocarcinoma patients.

Methods: Between December 1998 and May 2009, 85 patients aged ≤ 50 with lung adenocarcinoma were treated at our hospital. We examined 49 samples from adenocarcinoma patients who underwent surgical resection, chemotherapy, and/or radiotherapy for the EML4-ALK gene. None of the patients received ALK inhibitors because these drugs had not been approved in Japan before 2012. EML4-ALK fusion genes were screened using multiplex reverse-transcription PCR assay, and were confirmed by direct sequencing.

Results: The EML4-ALK fusion gene was detected in five tumors (10.2%). One patient had stage IB disease, one had stage IIIA, and three had stage IV. Histologically, there was one solid adenocarcinoma, two acinar adenocarcinomas, and two papillary adenocarcinomas. EML4-ALK fusion genes were mutually exclusive to EGFR and KRAS mutations. The five-year survival rate was 59.4% in patients without EML4-ALK fusion and was not reached in patients with EML4-ALK fusion.

Conclusion: The EML4-ALK fusion gene may be a strong oncogene in younger patients with lung adenocarcinoma.

Keywords: Adenocarcinoma; EML4-ALK; non-small cell lung cancer; young patient.

Figure 1

Histopathological results of EML4‐ALK fusion‐harboring tumors: (a,b) two acinar adenocarcinomas (cases 1 and 2), (c) one solid adenocarcinoma (case 3), and (d,e) two papillary adenocarcinomas (cases 4 and 5).

Figure 2

Kaplan–Meier plots of the overall survival of EML4‐ALK‐positive compared to EML4‐ALK‐negative patients. Overall survival was calculated from the date of initial therapy of the patients.