摘要
目的探讨癌相关成纤维细胞（CAF）CD10的表达及其在结直肠癌形成和演进中的作用。方法收集浙江宁波市鄞州第二医院有详细随访资料的结直肠癌手术切除标本226例，应用免疫组织化学法检测肿瘤组织中心区、癌旁腺瘤组织及切缘正常黏膜组织间质成纤维细胞CD10表达和肿瘤细胞Ki－67、p53、cyclin D1及β－catenin的表达，观察CD10在间质CAF中表达情况，分析其与肿瘤细胞表达Ki－67、p53、cyclin D1及β－catenin和临床病理参数的相关性。结果正常肠黏膜间质成纤维细胞不表达CD10，结直肠癌组织中心区和癌旁腺瘤区CAF CD10的表达率分别为80.1%（181/226）和58.4%（132/226），CD10阳性的细胞同时表达平滑肌肌动蛋白（SMA），不表达结蛋白。Ki－67在结直肠癌组织中心区和癌旁腺瘤区的肿瘤细胞表达率分别为84.1%（190/226）和63.7%（144/226），正常肠黏膜上皮表达率为7.1%（16/226）。p53在结直肠癌组织中心区和癌旁腺瘤区肿瘤细胞表达率分别为50.4%（114/226）和53.1%（120/226），在正常肠黏膜上皮的表达率为8.8%（20/226）。cyclin D1在结直肠癌组织中心区和癌旁腺瘤区肿瘤细胞表达率分别83.6%（189/226）和48.7%（110/226），在正常肠黏膜上皮不表达。β－catenin在正常肠黏膜上皮全部定位于细胞膜，癌旁腺瘤区肿瘤细胞膜表达率为53.1%（120/226），细胞质表达率为95.6%（216/226），细胞核表达率为10.6%（24/226）；肿瘤中心区癌细胞膜表达率为17.7%（40/226），细胞质表达率为100.0%（226/226），细胞核表达率为49.1%（111/226）。随着CAF CD10在癌旁腺瘤区和癌组织中心区的表达逐渐增高，周围肿瘤细胞Ki－67、p53、cyclin D1和β－catenin核表达也逐渐增高（P〈0.05）。CAF CD10在不同性别、不同年龄段和不同分化程度的癌组织中的表达率有差异（P〈0.05）；而与浸润深度、有无淋巴结转移及脉管癌栓无关（P〉0.05）。CD10阴性组的总体生存率优于CD10阳性组。结论CD10只在CAF中表达，高表达CD10的CAF与其邻近肿瘤细胞高表达p53、cyclin D1、Ki－67以及β－catenin的核表达呈正相关，CAF的标志物CD10与肿瘤细胞标志物p53、cyclin D1、Ki－67以及核β－catenin相结合，可以从肿瘤间质微环境的角度为结直肠癌病理诊断提供帮助；表达CD10的CAF通过激活Wnt信号促进肿瘤发生发展。
Objective To study CD10 expression in cancer-associated fibroblasts （CAF） and related effect on coloreetal cancer initiation and progression. Methods A total of 226 surgical removed eolorectal cancer specimens were collected with patient follow-up data. A panel of immunohistochemieal markers（CD10, Ki-67, p53, cyclin D1 and 13-catenin） were evaluated in carcinomas, adjacent adenomas and paired normal colorectal mucosa with correlation of clinicopathological parameters. Results CD10 expression was not detected in the normal eoloreetal mueosa by immunohistoehemistry. 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 mueosa. 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 eyelin 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-eatenin 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-eatenin 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, eyclin D1 and 13-eatenin in the tumor cells was positively associated with CD10 in CAF （ P 〈 0. 05 ）. The CDIO expression was different in patients with different gender, age and differentiation degree （ P 〈 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. Conclusions CDIO is only expressed in CAF. Signifieant correlation is found between CAF with high CDIO expression and neighboring tumor cells with p53, Ki-67 and cyclin D1 expression and nuclear β-eatenin expression. CDlO-positive CAF and p53, β-catenin, eyelin D1 and Ki-67-labelled eoloreetal cancer cells together with nuclear β-eatenin expression may provide helps for diagnosis of colorectal carcinoma from an angle of tumor interstitial microenvironment. CAF with CDIO expression may promote the initiation and progression of colon cancer cells by activating Wnt signaling pathway.
作者
朱音
郑江江
杨芳
聂倩倩
朱紫菱
邓红
Zhu Yin Zheng Jiangiiang Yang Fang Nie Qianqian Zhu Ziling Deng Hong(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)
出处
《中华病理学杂志》
CAS
CSCD
北大核心
2016年第12期859-865,共7页
Chinese Journal of Pathology
基金
国家自然科学基金（30870971）
浙江省自然科学基金（LY12H16027）
