Overexpression of the oncogenic signal transducer Gab2 occurs early in breast cancer development
Overexpression of the oncogenic signal transducer Gab2 occurs early in breast cancer development
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DOI：
10.1002/ijc.25172
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发表时间：
2010-09-15
影响因子：
6.4
通讯作者：
Daly, Roger J.
中科院分区：
文献类型：
--
作者：
Fleuren, Emmy D. G.;O'Toole, Sandra;Daly, Roger J.
Gab2是一种具有致癌潜力的停靠型信号蛋白，在乳腺癌中过表达，但其预后意义和在疾病演变中的作用尚不清楚。在一个已知结果的原发性人类乳腺癌的大型队列中对Gab2进行免疫组织化学检测，结果显示，虽然Gab2表达与肿瘤分级增加呈正相关，但在总队列或根据淋巴结、雌激素受体（ER）或HER2状态分层的患者中，Gab2表达与疾病复发或乳腺癌相关死亡无关。有趣的是，对包括癌前和浸润前乳腺病变以及转移性疾病样本的“进展系列”的分析显示，Gab2表达在检查的最早病变（通常的导管增生）中显著增强，在导管原位癌（DOS）中检测到进一步增加。此外，在浸润性癌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，虽然Gab2表达在乳腺癌中不是预后性的，但其在早期疾病演变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。
Gab2, a docking-type signaling protein with demonstrated oncogenic potential, is overexpressed in breast cancer, but its prognostic significance and rote 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 (DOS). 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.