Zhu Y, Zheng J J, Yang F, Nie Q Q, Zhu Z L, Deng H
Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
Department of Pathology, Yinzhou No.2 Hospital of Ningbo, Ningbo 315000, China.
Zhonghua Bing Li Xue Za Zhi. 2016 Dec 8;45(12):859-865. doi: 10.3760/cma.j.issn.0529-5807.2016.12.009.
To study CD10 expression in cancer-associated fibroblasts (CAF) and related effect on colorectal cancer initiation and progression. A total of 226 surgical removed colorectal cancer specimens were collected with patient follow-up data. A panel of immunohistochemical markers(CD10, Ki-67, p53, cyclin D1 and β-catenin) were evaluated in carcinomas, adjacent adenomas and paired normal colorectal mucosa with correlation of clinicopathological parameters. CD10 expression was not detected in the normal colorectal mucosa by immunohistochemistry. The percentages of CD10 expression in CAF were 80.1% (181/226) in carcinoma tissue and 58.4% (132/226) in adjacent adenomas, respectively. SMA was positive and desmin was negative. The proliferation index of Ki-67 was 84.1%(190/226) in tumor tissue, 63.7%(144/226)in adenoma zone, and 7.1% (16/226) in the normal mucosa. The rate of p53 mutation was 50.4% (114/226)in tumor tissue, 53.1%(120/226)in adenoma and 8.8%(20/226)in the normal mucosa. The expression rate of cyclin D1 was 83.6%(189/226) in tumor tissue, 48.7%(110/226)in adenoma zone, but negative in the normal mucosa. For normal tissue, the percentages of β-catenin expression was 53.1%(120/226), 95.6%(216/226) and 10.6%(24/226) in the cell membrane, cytoplasm and nucleus, respectively.The β-catenin expression in cell membrane, cytoplasm and nucleus was 17.7%(40/226), 100.0% (226/226) and 49.1% (111/226), respectively, in the tumor cells. The expression of Ki-67, p53, cyclin D1 and β-catenin in the tumor cells was positively associated with CD10 in CAF (<0.05). The CD10 expression was different in patients with different gender, age and differentiation degree (<0.05), whereas the depth of invasion, lymph node metastasis and tumor emboli did not relate to it. Overall survival rates in CD10 negative group were higher than that in CD10 positive group. CD10 is only expressed in CAF. Significant correlation is found between CAF with high CD10 expression and neighboring tumor cells with p53, Ki-67 and cyclin D1 expression and nuclear β-catenin expression. CD10-positive CAF and p53, β-catenin, cyclin D1 and Ki-67-labelled colorectal cancer cells together with nuclear β-catenin expression may provide helps for diagnosis of colorectal carcinoma from an angle of tumor interstitial microenvironment. CAF with CD10 expression may promote the initiation and progression of colon cancer cells by activating Wnt signaling pathway.
研究癌症相关成纤维细胞(CAF)中CD10的表达及其对结直肠癌发生和进展的相关影响。收集了226例手术切除的结直肠癌标本及患者随访数据。采用一组免疫组化标志物(CD10、Ki-67、p53、细胞周期蛋白D1和β-连环蛋白)对癌组织、相邻腺瘤及配对的正常结直肠黏膜进行评估,并分析其与临床病理参数的相关性。免疫组化检测显示正常结直肠黏膜中未检测到CD10表达。CAF中CD10在癌组织和相邻腺瘤中的表达率分别为80.1%(181/226)和58.4%(132/226)。平滑肌肌动蛋白(SMA)呈阳性,结蛋白呈阴性。肿瘤组织中Ki-67的增殖指数为84.1%(190/226),腺瘤区为63.7%(144/226),正常黏膜为7.1%(16/226)。肿瘤组织中p53突变率为50.4%(114/226),腺瘤中为53.1%(120/226),正常黏膜中为8.8%(20/226)。细胞周期蛋白D1在肿瘤组织中的表达率为83.6%(189/226),腺瘤区为48.7%(110/226),正常黏膜中为阴性。对于正常组织,β-连环蛋白在细胞膜、细胞质和细胞核中的表达率分别为53.1%(120/226)、95.6%(216/226)和10.6%(24/226)。肿瘤细胞中β-连环蛋白在细胞膜、细胞质和细胞核中的表达率分别为17.7%(40/226)、100.0%(226/226)和49.1%(111/226)。肿瘤细胞中Ki-67、p53、细胞周期蛋白D1和β-连环蛋白的表达与CAF中的CD10呈正相关(<0.05)。不同性别、年龄和分化程度的患者CD10表达不同(<0.05),而浸润深度、淋巴结转移和肿瘤栓子与CD10表达无关。CD10阴性组的总生存率高于CD10阳性组。CD10仅在CAF中表达。发现高表达CD10的CAF与邻近肿瘤细胞中p53、Ki-67和细胞周期蛋白D1表达及细胞核β-连环蛋白表达之间存在显著相关性。CD10阳性的CAF与p53、β-连环蛋白、细胞周期蛋白D1和Ki-67标记的结直肠癌细胞以及细胞核β-连环蛋白表达一起,可能从肿瘤间质微环境的角度为结直肠癌的诊断提供帮助。表达CD10的CAF可能通过激活Wnt信号通路促进结肠癌细胞的发生和进展。