Comparison of Clinicopathological Features and Prognosis between Rearrangements and Mutations in Surgically Resected Early-stage Lung Adenocarcinoma.

Background: A number of mutations in key oncogenes have been identified as important for the initiation and maintenance of lung adenocarcinoma (LAC). This study elucidated the prevalence and prognostic significance of mutations in the epidermal growth factor receptor gene () and rearrangements in the anaplastic lymphoma kinase gene () in patients with surgically resected primary LAC.

Patients And Methods: We retrospectively analyzed 675 consecutive patients who underwent radical resection at a single institution. We concurrently analyzed mutations in and the Kirsten rat sarcoma viral oncogene homolog gene () by reverse transcription (RT)-PCR, and investigated rearrangements by immunohistochemistry. LAC with or without various oncogenic mutations was studied for clinicopathological features and their association with disease-free survival (DFS) and overall survival (OS).

Result: rearrangements and mutations were detected in 75 and 312 patients, respectively, with coexistence in 5 cases. rearrangements and mutations in and were mutually exclusive. Compared with patients with mutations, rearrangements were more common in younger patients, and those with advanced tumors, lymph node metastases, and higher rates of postoperative adjuvant therapy. Histologically, mutations were more common than rearrangements in patients with the acinar predominant subtype and the lepidic predominant subtype of LAC, whereas rearrangements were more frequent in the solid predominant subtype with mucin production and invasive mucinous adenocarcinomas. -positive patients had a significantly worse DFS than those with mutations and wild-type (WT) patients. The mean OS after surgical procedures was significantly longer in -mutated versus WT patients. No significant differences were found in patients with -positive tumors compared with -mutated and WT patients.

Conclusion: Clinicopathological features of LAC with rearrangements differ from those of LAC with mutations. Patients with rearrangements had a significantly worse DFS than those harboring mutations. Thus, rearrangements are an adverse prognostic factor in surgically-resected LAC patients, while mutations are associated with a better prognosis.