Gene amplification and protein overexpression of MET are common events in ovarian clear-cell adenocarcinoma: their roles in tumor progression and prognostication of the patient
Gene amplification and protein overexpression of MET are common events in ovarian clear-cell adenocarcinoma: their roles in tumor progression and prognostication of the patient
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DOI：
10.1038/modpathol.2011.70
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发表时间：
2011-08-01
期刊：
影响因子：
7.5
通讯作者：
Matsubara, Osamu
中科院分区：
文献类型：
--
作者：
Yamamoto, Sohei;Tsuda, Hitoshi;Matsubara, Osamu
本研究的目的是评估卵巢透明细胞腺癌中MET蛋白的过表达和基因拷贝数的改变，并评估其作为新的治疗靶点的潜力。对90例透明细胞腺癌分别采用免疫组化和亮场双原位杂交技术检测MET蛋白过表达和MET基因拷贝数改变。此外，我们还对101例晚期非透明细胞型卵巢癌进行了评价比较。当在至少10%的肿瘤细胞中观察到中等或强强度的完全膜染色时，MET过表达被指定。当肿瘤表现出高水平的多体（>= 4拷贝，>= 40%的肿瘤细胞）或MET基因扩增时，双原位杂交确定为阳性。90例透明细胞腺癌中有20例（22%）检测到MET过表达，而111例非透明细胞型卵巢癌中未检测到MET过表达。89例透明细胞型腺癌中有21例（24%）双原位杂交阳性，而非透明细胞型卵巢癌只有3例（3%）。在整个人群中，MET基因的真正扩增仅在透明细胞腺癌组织学中检测到（5例，6%）。在透明细胞腺癌中，双原位杂交阳性与MET过表达和肿瘤低分化组织学高度相关（P分别为0.0105和0.00038）。对于透明细胞腺癌患者，MET过表达，以及肿瘤的晚期临床分期和低分化组织学，被确定为总体生存的一个独立的不利预后因素。总之，在卵巢癌中，MET原癌基因的扩增是高度选择性的，通常发生在透明细胞腺癌中。MET可以作为透明细胞腺癌患者预后和肿瘤进展的生物标志物，并有潜力作为透明细胞腺癌的新治疗靶点。现代病理学杂志（2011）24,1146-1155；doi: 10.1038 / modpathol.2011.70;2011年4月8日在线发布
The aim of this study was to assess protein overexpression and gene copy number alterations of MET in ovarian clear-cell adenocarcinoma, and to assess its potential as a novel therapeutic target. Ninety cases of clear-cell adenocarcinoma were analyzed for MET protein overexpression and copy number alterations of the MET gene by immunohistochemistry and brightfield double in situ hybridization, respectively. In addition, 101 cases of the non-clear-cell type ovarian carcinomas at advanced stages were also evaluated for comparison. MET overexpression was assigned when complete membrane staining with moderate or strong intensity was observed in at least 10% of the tumor cells examined. Double in situ hybridization was determined as positive when the tumor exhibited high-level polysomy (>= 4 copies in >= 40% of tumor cells) or MET gene amplification. MET overexpression was detected in 20 of 90 clear-cell adenocarcinomas (22%) and none of 111 non-clear-cell type ovarian carcinomas. Double in situ hybridization was positive in 21 of 89 informative clear-cell adenocarcinomas (24%) and only 3 non-clear-cell type ovarian carcinomas (3%). In the whole population, true amplification of the MET gene was detected only in the clear-cell adenocarcinoma histology (five cases, 6%). In clear-cell adenocarcinomas, double in situ hybridization positivity was highly correlated with the presence of MET overexpression and a poorly differentiated histology of tumors (P = 0.0105 and 0.00038, respectively). For the patients with clear-cell adenocarcinomas, MET overexpression, as well as advanced clinical stage and the poorly differentiated histology of tumors, was identified as an independent unfavorable prognostic factor for overall survival. In conclusion, among ovarian carcinomas, the amplification of the MET proto-oncogene is highly selective and commonly occurs in clear-cell adenocarcinoma. MET could serve as a biomarker for the prognostication of patients with clear-cell adenocarcinoma and tumor progression, and has potential as a novel therapeutic target for this carcinoma. Modern Pathology (2011) 24, 1146-1155; doi:10.1038/modpathol.2011.70; published online 8 April 2011