Prognostic significance of anaplastic lymphoma kinase rearrangement in patients with completely resected lung adenocarcinoma.

Reports of the prognostic significance of anaplastic lymphoma kinase (ALK) rearrangement in early stage lung adenocarcinoma have been contradictory. This study aimed to identify the associations of ALK rearrangement with clinicopathologic features and prognosis in patients with surgically resected stage I-IIIA lung adenocarcinoma. Analysis of ALK status was performed by a fully-automated immunochemistry assay (with rabbit monoclonal Ventana D5F3 antibody) in tissue sections of 2,103 patients with surgically-resected stage I-IIIA lung adenocarcinoma. ALK positive patients were matched with negative patients in a 1:1 ratio using propensity score matching (PSM). Clinical outcomes were assessed by disease-free survival (DFS) and overall survival (OS) after surgery. Initial recurrence pattern was also investigated according to ALK status. Among 2,103 stage I-IIIA lung adenocarcinoma cases, 81 (3.9%) were ALK positive. ALK positivity was significantly associated with younger age (P<0.001), solid predominant adenocarcinoma (P<0.001), variants of invasive adenocarcinoma (P<0.001), higher frequency of pleura invasion (P=0.040), smaller tumor size (P=0.014), mediastinal lymph node involvement (N2; P<0.001) and later pathologic stage (IIIA; P=0.001). In the match cohort, ALK positivity was not associated with DFS [hazard ratio (HR), 0.58; 95% confidence interval (CI): 0.33-1.03, P=0.063] or OS (HR, 0.61; 95% CI: 0.22-1.67, P=0.334). Lymph node involvement (HR: 5.36, 95% CI, 3.01-9.65, P<0.001) and solid predominant adenocarcinoma subtype (HR, 2.02; 95% CI: 1.07-3.79; P=0.029) were the independent prognostic factors of inferior DFS, and lymph node involvement was the independent prognostic factors of worse OS (HR, 6.61; 95% CI: 2.43-17.94; P<0.001). ALK positive patients had a higher risk of developing tumor recurrence in liver (P=0.043). ALK rearrangement was not an independent prognostic factor in stage I-IIIA lung adenocarcinoma patients but leaded to a higher risk of developing recurrence in liver.

Liu Y ，Ye X ，Yu Y ，Lu S ... -  《-》

Worse disease-free, tumor-specific, and overall survival in surgically-resected lung adenocarcinoma patients with ALK rearrangement.

Gao Q ，Li P ，Jiang X ，Zhan Z ，Yan Q ，Zhang B ，Huang C ... -  《Oncotarget》

Anaplastic lymphoma kinase rearrangement in surgically resected stage IA lung adenocarcinoma.

Shin SH ，Lee H ，Jeong BH ，Choi YS ，Shin MH ，Kim S ，Han J ，Lee KS ，Shim YM ，Kwon OJ ，Kim H ... -  《-》

Clinicopathological and Prognostic Significance of EML4-ALK Rearrangement in Patients with Surgically Resected Lung Adenocarcinoma: A Propensity Score Matching Study.

The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is a key oncogenic driver in non-small cell lung cancer (NSCLC). This study analyzed the clinicopathological characteristics and prognostic significance of EML4-ALK fusion gene in patients with surgically resected adenocarcinoma. The clinicopathological characteristics of 1056 consecutive patients with surgically resected stage I-IIIA adenocarcinoma were collected from February 2014 to October 2014, and EML4-ALK rearrangement was detected using real-time polymerase chain reaction (RT-PCR) technology. To compare the imaging and pathological features, a propensity score matching (PSM) method was performed. The follow-up information was collected to evaluate the long-term outcomes of patients with EML4-ALK rearrangement. The prevalence of EML4-ALK rearrangement was 6.6% in 1056 consecutive patients. A total of 70 EML4-ALK-positive and 210 EML4-ALK-negative patients were identified after PSM. Imaging and pathological analyses showed that EML4-ALK rearrangement was significantly associated with less ground-glass opacity (GGO) (adjusted OR=1.38, 95% CI=1.03-1.85, Ptrend =0.029) and higher prevalence of non-invasive mucinous adenocarcinoma mucin-laden adenocarcinomas (non-IMA MLA, adjusted OR=6.79, 95% CI=2.69-17.17, P<0.001). EML4-ALK rearrangement was found to be an unfavorable prognostic factor for disease-free survival (DFS) in female patients (HR=2.26, 95% CI=1.13-4.53, P=0.021). Our results suggest that adenocarcinomas harboring EML4-ALK fusion gene exhibit specific radiological and pathological characteristics compared with EML4-ALK-negative adenocarcinomas. In female patients, EML4-ALK rearrangement was associated with shorter DFS.

Shi J ，Gu W ，Zhao Y ，Zhu J ，Jiang G ，Bao M ，Shi J ... -  《Cancer Management and Research》

Resected stage I anaplastic lymphoma kinase-positive lung adenocarcinoma has a negative impact on recurrence-free survival.

The clinical and prognostic implications of anaplastic lymphoma kinase (ALK) status in resected lung cancers remain unclear. In this study we analyzed the prognostic and predictive significance of ALK-positive among patients with completely resected lung adenocarcinoma. We retrospectively reviewed 197 patients with lung adenocarcinoma who underwent complete surgical resection and had been tested for their ALK status. We investigated the impact of an ALK-positive status on the recurrence-free survival (RFS) and overall survival (OS) and examined the predictive factors for an ALK-positive status. ALK positivity was noted in 36 (18%) out of 197 patients, and when limited to stage I patients, in 24 (19%) out of 124. In the pathological-stage I population, while the OS exhibited no significant difference between ALK-positive and ALK-negative patients (5-year OS rate, 81.2% vs. 89.8%, p = 0.226), the RFS of ALK-positive patients was significantly worse than that of ALK-negative patients (5-year RFS rate, 55.9% vs. 78.8%, p = 0.018). A multivariate analysis showed that ALK-positive status (hazard ratio [HR] 3.431, p = 0.009) was an independent prognostic factor for the RFS. Regarding the relationship between clinicopathological factors and an ALK-positive status, a high-grade histological subtype, including solid and micropapillary subtypes (odds ratio [OR] 5.464, p < 0.001), and never-smokers (OR 4.292, p = 0.018) were associated with ALK-positive. A high-grade histological subtype and never-smokers were associated with ALK positivity, and the RFS of ALK-positive patients was worse than that of ALK-negative patients among patients with completely resected stage I lung adenocarcinoma.

Fujibayashi Y ，Tane S ，Kitazume M ，Kuroda S ，Kimura K ，Kitamura Y ，Nishio W ... -  《-》