Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Int J Cancer. 2010 Sep 1;127(6):1486-92. doi: 10.1002/ijc.25172.
Gab2, a docking-type signaling protein with demonstrated oncogenic potential, is overexpressed in breast cancer, but its prognostic significance and role in disease evolution remain unclear. Immunohistochemical detection of Gab2 in a large cohort of primary human breast cancers of known outcome revealed that while Gab2 expression was positively correlated with increased tumor grade, it did not correlate with disease recurrence or breast cancer-related death in the total cohort or in patients stratified according to lymph node, estrogen receptor (ER) or HER2 status. Interestingly, analysis of a "progression series" that included premalignant and preinvasive breast lesions as well as samples of metastatic disease revealed that Gab2 expression was significantly enhanced in the earliest lesion examined, usual ductal hyperplasia, with a further increase detected in ductal carcinoma in situ (DCIS). Furthermore, expression was less in invasive cancers and lymph node metastases than in DCIS, but still higher than in normal breast. These findings indicate that while Gab2 expression is not prognostic in breast cancer, its role in early disease evolution warrants further analysis, as Gab2 and its effectors may provide targets for novel strategies aimed at preventing breast cancer development.
Gab2 是一种衔接型信号蛋白，具有明确的致癌潜能，在乳腺癌中过表达，但它在疾病进展中的预后意义和作用仍不清楚。对已知结局的大量原发性人乳腺癌进行 Gab2 的免疫组化检测表明，尽管 Gab2 的表达与肿瘤分级增加呈正相关，但在总队列中或根据淋巴结、雌激素受体 (ER) 或 HER2 状态分层的患者中，Gab2 的表达与疾病复发或乳腺癌相关的死亡均无相关性。有趣的是，对包括癌前和侵袭前乳腺病变以及转移性疾病样本的“进展系列”分析表明，Gab2 的表达在最早检查到的病变——普通导管增生中显著增强，在导管原位癌 (DCIS) 中进一步增加。此外，浸润性癌症和淋巴结转移中的表达低于 DCIS，但仍高于正常乳腺。这些发现表明，尽管 Gab2 的表达在乳腺癌中没有预后意义，但它在早期疾病进展中的作用值得进一步分析，因为 Gab2 及其效应物可能为旨在预防乳腺癌发展的新策略提供靶点。
