Correlation of anaplastic lymphoma kinase overexpression and the EML4-ALK fusion gene in non-small cell lung cancer by immunohistochemical study.
BACKGROUND
Recently the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene with transforming activity was identified in non-small cell lung cancer (NSCLC). In addition, NSCLC patients with the EML4-ALK fusion gene had a dramatic response and longer progression free survival after ALK inhibitor treatment than those without this fusion gene. However, the incidence and clinical and molecular characteristics of the EML4-ALK fusion gene in NSCLC patients of Taiwan are still unclear.


METHODS
Sixty-four fresh frozen tumor specimens were obtained from the tissue bank of Chang Gung Memorial Hospital for RNA extraction and EML4-ALK fusion gene detection. Paraffin sections of lung tumors from all of these patients were available and were analyzed for ALK protein expression by immunohistochemical (IHC) study. The results were correlated with clinical and molecular biomarkers.


RESULTS
Three of the 64 tumors (4.7%) had the EML4-ALK fusion gene. Two were adenocarcinomas, and one was adenosquamous carcinoma. Twenty patients with non-squamous cell carcinomas had epidermal growth factor receptor (EGFR) mutations, so the EML4-ALK fusion gene was found in 14.3% of EGFR wild type non-squamous cell carcinomas. Two tumors were variant 3 (3a+3b with 3b predominant) and had strong staining (3+) for ALK by IHC stains. One tumor was variant 1 and had moderate staining (2+) for ALK. None of the ALK wild type tumors had strong staining for ALK. When compared with other clinical and molecular features, only the IHC stain for ALK was significantly correlated with the EML4-ALK fusion gene (p = 0.0002).


CONCLUSIONS
ALK overexpression detected by IHC study could be a promising detection method for the EML4-ALK fusion gene and is worth further confirmation with more samples.
Department of Pathology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Tai-Di
TD
Chen
Il-Chi
IC
Chang
Hui-Ping
HP
Liu
Yi-Cheng
YC
Wu
Chi-Liang
CL
Wang
Ya-Ting
YT
Chen
Yi-Rong
YR
Chen
Shiu-Feng
SF
Huang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*
C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases