Clinicopathological and Survival Analysis of Japanese Patients with Resected Non-Small-Cell Lung Cancer Harboring NKX2-1, SETDB1, MET, HER2, SOX2, FGFR1, or PIK3CA Gene Amplification

被引：42

作者：

Inoue, Yusuke ^{[1
,2
]}

Matsuura, Shun ^{[1
,2
]}

Kurabe, Nobuya ^{[1
]}

Kahyo, Tomoaki ^{[1
]}

Mori, Hiroki ^{[3
]}

Kawase, Akikazu ^{[4
]}

Karayama, Masato ^{[2
,5
]}

Inui, Naoki ^{[2
,6
]}

Funai, Kazuhito ^{[4
]}

Shinmura, Kazuya ^{[1
]}

Suda, Takafumi ^{[2
]}

Sugimura, Haruhiko ^{[1
]}

机构：

[1] Hamamatsu Univ Sch Med, Dept Tumor Pathol, Hamamatsu, Shizuoka 4313192, Japan

[2] Hamamatsu Univ Sch Med, Dept Internal Med, Div 2, Hamamatsu, Shizuoka 4313192, Japan

[3] Hamamatsu Med Ctr, Dept Pathol, Hamamatsu, Shizuoka, Japan

[4] Hamamatsu Univ Sch Med, Dept Surg 1, Hamamatsu, Shizuoka 4313192, Japan

[5] Hamamatsu Univ Sch Med, Clin Oncol, Hamamatsu, Shizuoka 4313192, Japan

[6] Hamamatsu Univ Sch Med, Clin Pharmacol & Therapeut, Hamamatsu, Shizuoka 4313192, Japan

来源：

JOURNAL OF THORACIC ONCOLOGY | 2015年 / 10卷 / 11期

基金：

日本学术振兴会;

关键词：

Non-small-cell lung cancer; Gene amplification; Coamplification; NKX2-1; SETDB1; IN-SITU HYBRIDIZATION; INDEPENDENT PROGNOSTIC-FACTOR; COPY NUMBER; PROTEIN EXPRESSION; GEFITINIB THERAPY; 3Q AMPLIFICATION; ADENOCARCINOMA; RESISTANCE; CARCINOMAS; ONCOGENE;

D O I：

10.1097/JTO.0000000000000685

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Gene amplification is an important genetic change in cancer cells. We investigated the prevalence, clinicopathological characteristics, and prognostic value of NKX2-1 (also known as TTF-1), SETDB1, MET, HER2, SOX2, FGFR1, and PIK3CA amplification in Japanese patients with non-small-cell lung cancer (NSCLC). Methods: The copy numbers of the seven above-mentioned genes were assessed using fluorescence in situ hybridization in a tissue microarray containing 282 surgically resected NSCLC specimens (164 adenocarcinoma [AC], 99 squamous cell carcinoma [SCC], and 19 others). Clinicopathological information were obtained from the medical records. Results:NKX2-1, SETDB1, MET, HER2, SOX2, FGFR1, and PIK3CA gene amplification were observed in 30 of 277 (10.8%), 16 of 280 (5.7%), 38 of 278 (13.7%), 8 of 270 (3.0%), 34 of 278 (12.2%), 18 of 282 (6.4%), and 53 of 278 (19.1%) cases, respectively. Coamplification was detected in 16 of 156 (10.3%) AC patients and 35 of 93 (37.6%) SCC patients (p < 0.0001). NKX2-1 amplification was significantly related to an AC histology (p = 0.004), whereas SOX2, FGFR1, and PIK3CA amplifications were related to a SCC histology (p < 0.0001). Within the ACs, NKX2-1 and SETDB1 amplifications were markers of a shorter survival period. A multivariate Cox proportional hazards model revealed that NKX2-1 amplification was an independent predictor of poor survival (hazard ratio, 2.938; 95% confidence interval, 1.434-6.022; p = 0.003). Coamplification had impact on patient outcome in AC but not in entire NSCLC and SCC. Conclusions: The amplification status differed among the histological types of NSCLC. NKX2-1 amplification was an independent and the most practically important predictor of a poor prognosis among Japanese patients with AC.

引用

页码：1590 / 1600

页数：11

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