Anaplastic lymphoma kinase fusion protein expression is associated with a favorable prognosis in resected invasive mucinous lung adenocarcinoma: A retrospective study from two Chinese tertiary hospitals

Background: Invasive mucinous adenocarcinoma (IMA) is a distinct variant of lung adenocarcinoma, which typically has a worse survival. However, its pathogenesis is potentially associated with a high degree of molecular heterogeneity, which might determine its different prognosis.

Methods: We retrospectively analyzed 2207 consecutive lung adenocarcinoma patients who underwent radical resection at Qilu Hospital of Shandong University and Shandong Provincial Hospital from 2013 to 2019. Anaplastic lymphoma kinase (ALK) fusion protein expression was routinely detected by immunohistochemistry. The clinicopathological characteristics and treatment outcomes of IMA patients were retrieved, and compared between ALK-positive and ALK-negative IMA patients as well as between pure IMA and mixed IMA patients. The last follow-up was on December 31, 2020, and the median follow-up was 42 months.

Results: A total of 98 patients (4.4%) were diagnosed with IMA. ALK protein expression was positive in 24.5% of IMAs, which was significantly higher than that of non-IMA lung adenocarcinomas (4.7%, P < 0.001). ALK-positive and ALK-negative IMA, as well as pure IMA and mixed IMA, showed similar distribution in terms of patients' age, gender and smoking history, stage, and primary tumor location, except for a higher rate of lymph node metastasis in mixed IMA (22.0% vs. 46.2%, P = 0.012). Five cases (20.8%) of ALK-positive IMAs and 28 cases (40.6%) of ALK-negative IMAs experienced recurrence. Multivariable-adjusted Cox regression analysis demonstrated that ALK expression was a favorable prognostic factor for both disease-free survival (hazard ratio [HR]: 0.354; 95% confidence interval [CI]: 0.131-0.960; P = 0.041) and overall survival (HR: 0.138; 95% CI: 0.029-0.658; P = 0.013) in resected IMA. No difference in disease-free survival (HR: 0.524; 95% CI: 0.237-1.157; P = 0.110) and OS (HR: 0.553; 95% CI: 0.199-1.537; P = 0.256) was observed between pure IMA and mixed IMA.

Conclusion: Invasive mucinous lung adenocarcinoma showed higher ALK protein expression, which was a favorable prognostic factor for survival in early resected patients.