ECT2 amplification and overexpression as a new prognostic biomarker for early-stage lung adenocarcinoma.
Genetic abnormality in early-stage lung adenocarcinoma was examined to search for new prognostic biomarkers. Six in situ lung adenocarcinomas and nine small but invasive adenocarcinomas were examined by array-comparative genomic hybridization, and candidate genes of interest were screened. To examine gene abnormalities, 83 cases of various types of lung carcinoma were examined by quantitative real-time genomic PCR and immunohistochemistry. The results were then verified using another set of early-stage adenocarcinomas. Array-comparative genomic hybridization indicated frequent amplification at chromosome 3q26. Of the seven genes located in this region, we focused on the epithelial cell transforming sequence 2 (ECT2) oncogene, as ECT2 amplification was detected only in invasive adenocarcinoma, and not in in situ carcinoma. Quantitative PCR and immunohistochemistry analyses also detected overexpression of ECT2 in invasive adenocarcinoma, and this was correlated with both the Ki-67 labeling index and mitotic index. In addition, it was associated with disease-free survival and overall survival of patients with lung adenocarcinoma. These results were verified using another set of early-stage adenocarcinomas resected at another hospital. Abnormality of the ECT2 gene occurs at a relatively early stage of lung adenocarcinogenesis and would be applicable as a new biomarker for prognostication of patients with lung adenocarcinoma.
Department of Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Yoshihiko
Y
Murata
Yuko
Y
Minami
Reika
R
Iwakawa
Jun
J
Yokota
Shingo
S
Usui
Koji
K
Tsuta
Kouya
K
Shiraishi
Shingo
S
Sakashita
Kaishi
K
Satomi
Tatsuo
T
Iijima
Masayuki
M
Noguchi
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D014408:Biomarkers, Tumor; D018572:Disease-Free Survival; D055088:Early Detection of Cancer; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; C489850:ECT2 protein, human; D011518:Proto-Oncogene Proteins
3q26 Region; ECT2; array-comparative genomic hybridization; early-stage lung adenocarcinoma; prognostic biomarker