J Cancer 2016; 7(15):2207-2212. doi:10.7150/jca.16768

Research Paper

Clinicopathological features and relation between anaplastic lymphoma kinase (ALK) mutation and histological subtype of lung adenocarcinoma in Eastern European Caucasian population

Bojan Zaric1, Vladimir Stojsic1, Milana Panjkovic1, Dragana Tegeltija1, Vanesa Stepanov1, Tomi Kovacevic1, Tatjana Sarcev1, Davorin Radosavljevic2, Aleksandar Milovancev1, Vasilis Adamidis1, Paul Zarogoulidis3✉, Wolfgang Hohenforst-Schmidt4, Georgia Trakada5, Aggeliki Rapti6, Branislav Perin1

1. Institute for Pulmonary Diseases of Vojvodina, Faculty of Medicine, University of Novi Sad, Serbia;
2. Institute of Oncology and Radiology of Serbia, Belgrade, Serbia;
3. Pulmonary Oncology Unit, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece;
4. Medical Clinic I, ''Fuerth'' Hospital, University of Erlangen, Fuerth, Germany;
5. Division of Pulmonology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Alexandra Hospital, Athens, Greece;
6. Pulmonary Department, ''Sotiria '' Hospital of Chest Diseases, Athens, Greece.

Abstract

Introduction: The incidence of echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) mutation among surgically treated patients with adenocarcinoma of the lung of the Eastern European ethnicity is underreported. The aim of this trial was the determination of EML4-ALK mutation frequency in investigated population, and the evaluation of correlations between lung adenocarcinoma subtype and clinical characteristics with mutation status.

Patients and methods: This was a prospective trial which included 195 patients with adenocarcinoma of the lung who underwent surgical treatment. ALK mutation screening was performed by immunohistochemistry (IHC). IHC scores of 2+ and 3+ were regarded as positive. Confirmatory FISH was performed in all IHC positive and in 2:1 ratio in negative patients.

Results: Overall ALK mutation rate established by IHC was 6.2%, while FISH confirmed rate of 5.1%. The FISH confirmed ALK positivity in 7.6% Hungarians, 5.5% Serbians, and 6.6% Slovakians. Acinar subtype of adenocarcinoma of the lung was significantly (p=0.02) related to EML4-ALK positive mutation status. Most of the patients were males (56.9%), smokers (50.8%), or former smokers (28.7%) with acinar (55.4%) or solid (35.9%) adenocarcinoma of the lung. Sensitivity and specificity of IHC were 100% and 98.9% respectively.

Conclusions: ALK mutation rate in surgically treated patients with adenocarcinoma of the lung was found to be 6.2% by IHC and 5.1% by FISH. Acinar subtype of the adenocarcinoma of the lung was significantly related to ALK positive mutation.

Keywords: adenocarcinoma of the lung, anaplastic lymphoma kinase (ALK), EML4-ALK translocation, non-small cell lung cancer

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How to cite this article:
Zaric B, Stojsic V, Panjkovic M, Tegeltija D, Stepanov V, Kovacevic T, Sarcev T, Radosavljevic D, Milovancev A, Adamidis V, Zarogoulidis P, Hohenforst-Schmidt W, Trakada G, Rapti A, Perin B. Clinicopathological features and relation between anaplastic lymphoma kinase (ALK) mutation and histological subtype of lung adenocarcinoma in Eastern European Caucasian population. J Cancer 2016; 7(15):2207-2212. doi:10.7150/jca.16768. Available from http://www.jcancer.org/v07p2207.htm