表皮生长因子受体家族配体和受体在胃癌中的表达。

Expression of the ERBB Family of Ligands and Receptors in Gastric Cancer.

机构信息

Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Pathobiology. 2017;84(4):210-217. doi: 10.1159/000464250. Epub 2017 Apr 12.

DOI:10.1159/000464250

PMID:28399526

Abstract

OBJECTIVE

Gastric cancer (GC) is the second most common cancer and the third leading cause of cancer-related death in Korea. Alterations in the ERBB (homology to the erythroblastoma viral gene product, v-erbB) receptor family and ERBB-related signaling pathways are frequently observed in GC. However, the roles of the ERBB receptors and their ligands in GC are not well established.

METHODS

We evaluated the expression levels of various ERBB receptor ligands (i.e., heparin-binding epidermal growth factor-like growth factor [HBEGF], transforming growth factor-α [TGFA], amphiregulin [AREG], epiregulin [EREG], epidermal growth factor [EGF], and betacellulin [BTC]) and 3 ERBB family receptors (i.e., epidermal growth factor receptor [EGFR], human EGFR2 [HER2], and ERBB3) in 313 cases of GC using immunohistochemistry, fluorescence in situ hybridization, and mRNA in situ hybridization.

RESULTS

A high expression of EGFR, HER2, and ERBB3 was observed in 30, 32, and 27 cases, respectively. A high expression of HBEGF, TGFA, AREG, EREG, EGF, and BTC was observed in 91, 97, 151, 74, 26, and 37 cases, respectively. A high expression of TGFA was associated with better survival, while a high expression of BTC was associated with worse survival. These results were confirmed using Cox proportional hazards analysis. HBEGF, TGFA, AREG, tumor-node-metastasis classification, Lauren's classification, and ERBB3 were significant survival parameters in multivariate analysis.

CONCLUSION

Among the ERBB family receptors and ligands examined, 3 ligands (i.e., TGFA, HBEGF, and AREG) and ERBB3 had a prognostic impact.

摘要

目的

胃癌（GC）是韩国第二常见的癌症和第三大癌症相关死亡原因。ERBB（与成红细胞病毒产物，v-erbB 同源）受体家族和 ERBB 相关信号通路的改变在 GC 中经常观察到。然而，ERBB 受体及其配体在 GC 中的作用尚未得到很好的确定。

方法

我们使用免疫组织化学、荧光原位杂交和 mRNA 原位杂交评估了 313 例 GC 中各种 ERBB 受体配体（即肝素结合表皮生长因子样生长因子[HBEGF]、转化生长因子-α[TGFA]、双调蛋白[AREG]、上皮调节素[EREG]、表皮生长因子[EGF]和β细胞素[BTC]）和 3 个 ERBB 家族受体（即表皮生长因子受体[EGFR]、人表皮生长因子受体 2[HER2]和 ERBB3）的表达水平。

结果

观察到 30 例、32 例和 27 例 EGFR、HER2 和 ERBB3 高表达。HBEGF、TGFA、AREG、EREG、EGF 和 BTC 高表达分别见于 91、97、151、74、26 和 37 例。TGFA 高表达与生存改善相关，而 BTC 高表达与生存恶化相关。这些结果通过 Cox 比例风险分析得到证实。HBEGF、TGFA、AREG、肿瘤-淋巴结-转移分类、Lauren 分类和 ERBB3 是多变量分析中的显著生存参数。