Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations

Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations
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DOI:
10.1038/modpathol.3800960
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发表时间:
2007-12-01
期刊:
影响因子:
7.5
通讯作者:
Fischer, Andrew H.
Fischer, Andrew H.
中科院分区:
医学1区
文献类型:
--
作者:
Li, Cuizhen;Zota, Victor;Fischer, Andrew H.

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胰岛素样生长因子-Ⅱ mRNA结合蛋白3(Insulin-like growth factor-II mRNA-binding protein 3,IMP3)是一种新发现的癌胚mRNA结合蛋白,参与胚胎发生和某些恶性肿瘤的发生。为了研究这种蛋白在子宫内膜癌中的诊断和临床病理学意义,我们评估了IMP3在两种最常见的子宫内膜恶性肿瘤,子宫内膜样腺癌和浆液性癌中的免疫组化表达。我们选择了167例子宫内膜腺癌患者,其中子宫内膜样腺癌122例,浆液性癌45例。20例子宫良性病变患者的20例良性子宫内膜标本作为对照。IMP3免疫组化染色在所有浆液性癌中均呈阳性,其中IMP3免疫反应阳性肿瘤细胞数> 50%者39例(86%),IMP3免疫反应阳性肿瘤细胞数21- 50%者3例(7%),IMP3免疫反应阳性肿瘤细胞数6-20%者3例(7%)。免疫组化显示,38例(84%)浆液性癌中IMP3的反应强度为强,7例(16%)为中等。54例(44%)乳腺样腺癌IMP 3阴性。30例(25%)、20例(16%)、10例(8%)和8例(7%)类胶质瘤样腺癌在1-5、6-20、21-50和> 50%的肿瘤细胞中表现出IMP 3阳性免疫反应性。在34例(28%)乳腺癌样腺癌中观察到强IMP 3染色强度,26例(21%)中等强度,8例(7%)弱染色强度。所有20例对照病例均为IMP 3阴性。为了比较p53和IMP 3的表达,我们发现35例(78%)浆液性癌在> 50%的肿瘤细胞核中显示出强的p53免疫组化活性。与此相反,112例乳腺样腺癌中有11例(10%)在> 50%的肿瘤细胞核中表现出强p53阳性。总之,我们的研究结果表明,与浆液性腺癌相比,IMP 3在浆液性腺癌中的表达显著(P < 0.0001)。IMP3和p53的表达可能是鉴别子宫内膜浆液性癌和子宫内膜样腺癌的重要指标。此外,IMP3在类胶质瘤样腺癌中的表达与肿瘤的较高核分级和结构分级相关(分别为P=0.0000和P=0.0002)。
Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) is a newly identified oncofetal mRNA-binding protein that is involved in embryogenesis and carcinogenesis of some malignant neoplasms. To investigate the diagnostic and clinicopathologic significance of this protein in endometrial carcinomas, we evaluated immunohistochemical expression of IMP3 in the two most common forms of endometrial malignancies, endometrioid adenocarcinoma and serous carcinoma. We selected 167 endometrial adenocarcinoma cases including 122 cases of endometrioid adenocarcinoma and 45 cases of serous carcinoma. Twenty samples of benign endometrium obtained from 20 patients with nonmalignant uterine lesions were used as controls. Positive immunohistochemical stain for IMP3 was identified in all serous carcinoma cases, among which, 39 (86%) and 3 (7%) cases showed IMP3 immunoreactivity in > 50%, and 21-50, or 6-20% of tumor cells, respectively. Immunohistochemical reaction intensity for IMP3 was identified to be strong in 38 (84%) and intermediate in 7 (16%) cases of serous carcinoma. Fifty-four (44%) cases of endometrioid adenocarcinoma were negative for IMP3. Thirty (25%), 20 ( 16%), 10 (8%), and 8 ( 7%) cases of endometrioid adenocarcinoma demonstrated positive immunoreactivity for IMP3 in 1-5, 6-20, 21-50, and > 50% of the tumor cells. Strong IMP3-staining intensity was noted in 34 (28%), intermediate in 26 (21%), and weak in 8 ( 7%) cases of endometrioid adenocarcinoma. All 20 control cases were negative for IMP3. To compare p53 with IMP3 expressions, we found that 35 (78%) of the serous carcinoma cases showed strong p53 immunohistochemical activity in > 50% of the tumor cell nuclei. In contrast, 11 of 112 (10%) endometrioid adenocarcinoma cases demonstrated strong p53 positivity in > 50% of the tumor cell nuclei. In conclusion, our findings demonstrate significant expression of IMP3 in serous carcinoma as compared to endometrioid adenocarcinoma ( P < 0.0001). Expression of IMP3 and p53 may be helpful biomarkers in the distinction of endometrial serous carcinoma from endometrioid adenocarcinoma. In addition, expression of IMP3 in endometrioid adenocarcinoma correlates with higher nuclear and architecture grades of the tumor ( P=0.0000 and P=0.0002, respectively).