Abstract
Patients with lung adenocarcinoma who harbor ALK gene rearrangements can demonstrate significant clinical benefit with ALK tyrosine kinase inhibitors. Insulin-like growth factor receptor 1 (IGFR1) is a cellular membrane receptor that is overexpressed in many tumors. It plays an important role in cancer progression and is associated with increased postoperative recurrence and poorer disease-free survival. The aim of this study was to determine the EML4-ALK mutation and IGFR1 expression in lung adenocarcinoma and analyze their prognostic value. In this study, we analyzed the EML4-ALK mutation using the FISH and IHC techniques in 251 lung adenocarcinoma (203 primary resections, 48 metastasectomies) cases. Correlative analyses were performed between the EML4-ALK mutation, the IGFR1, TTF1, and NapsinA expression, and the clinicopathologic factors in lung adenocarcinomas. The EML4-ALK mutation was observed in 3.8% of the cases and it was associated with the solid pattern, signet ring cell morphology, and larger tumor size. IGFR1 expression was identified in 49% of the cases and most of the ALK-mutated cases were also expressing the IGFR1 protein (66%). IGFR1 expression frequency was increased in metastasectomy specimens. A solid signet-ring cell pattern or mucinous cribriform pattern was present at least focally in all ALK-positive tumors, consistently with the literature. In addition, IGFR1 expression levels showed an increase in the EML4-ALK-mutated cases in our series, but the clinical significance of this finding should be supported by larger series and survival analysis. Our findings show that IGFR1 expression may be useful as a poor prognostic marker in patients with lung adenocarcinoma.
Highlights
Lung cancer is the most frequent cause of cancer deaths, accounting for approximately 1.6 million deaths per year worldwide [1]
The Echinoderm microtubule-associated proteinlike 4’ (EML4)-Anaplastic lymphoma kinase‘ (ALK) mutation was observed in 3.8% of the cases and it was associated with the solid pattern, signet ring cell morphology, and larger tumor size
Insulin-like growth factor receptor 1 (IGFR1) expression was identified in 49% of the cases and most of the ALK-mutated cases were expressing the IGFR1 protein (66%)
Summary
Lung cancer is the most frequent cause of cancer deaths, accounting for approximately 1.6 million deaths per year worldwide [1]. Many studies on lung cancer carcinogenesis have been conducted over the years. These studies are especially important for clinical treatment strategies and the development of targeted therapies. Translocation and inversion of the ‘Anaplastic lymphoma kinase‘ (ALK) gene with ‘Echinoderm microtubule-associated proteinlike 4’ (EML4) has been detected in a subset of nonsmall cell lung cancer (NSCLC) patients in 2007 [4]. Several studies have shown that certain patient characteristics such as younger age, never or light smoker, signet ring cell morphology, and adenocarcinoma subtype increase the probability of finding an ALK mutation [9,10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
