CK10和CK17在早期宫颈癌组织中的表达及其预测预后的价值
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摘要
目的:CK10和CK17在早期宫颈癌组织中的表达及其预测预后价值的意义。方法:采用标准免疫组化SP法检测CK10和CK17在60例正常宫颈组织、60例宫颈上皮内瘤变和120例宫颈癌组织中的表达情况。结果:CK10的阳性表达定位于细胞质,在正常宫颈组织、CIN、宫颈癌患者中阳性表达率分别为80.00%、50.00%和21.67%,三组相比差异有显著统计学意义(P<0.001)。CK17的阳性表达定位于细胞质,三组阳性表达率分别为0%、46. 67%和80. 00%,三组相比差异显著(P <0. 001)。χ2检验分析宫颈癌组织中CK17的表达与患者FIGO分期、是否有淋巴结转移、病理分型、组织分化无关(P> 0. 05); CK10的表达与患者FIGO分期、是否有淋巴结转移、病理分型无关,与组织分化程度有关(P=0. 021)。Kaplan-Meier生存分析显示:早期宫颈癌手术治疗患者的1年、3年、5年生存率分别为:100%、96. 7%、93. 3%; CK10阴性组和阳性组5年生存率分别为91. 5%和100%; CK17阴性组和阳性组5年生存率分别为100%和91. 7%,差异均无统计学意义(P> 0. 05)。单因素分析显示CK10及CK17的表达和预后无关(P> 0. 05),年龄、是否淋巴结转移、FIGO分期、组织分化、病理分型均与预后相关(P <0. 05)。根据CK17和CK10的表达情况将患者分为四组,CK17阳性CK10阴性组患者1年、3年、5年生存率分别为:100%、94. 9%、89. 7%,余CK17阳性CK10阳性组、CK17阴性CK10阳性组、CK17阴性CK10阴性组5年生存率分别为:100%、100%、100%,差异无统计学意义(P=0. 211)。结论:CK10的表达水平与宫颈病变严重程度呈负相关,CK17的表达水平与宫颈病变严重程度呈正相关,两者可能参与了宫颈癌的发生发展,但CK17和CK10在预测宫颈癌患者预后方面的价值不大,而年龄、是否淋巴结转移、FIGO分期、组织分化、病理分型是影响患者预后的重要因素。
Objective:To study the expression and prognostic value of CK10 and CK17 in patients undergoing early cervical cancer surgery.Methods:Standard immunohistochemical SP method was used to detect the expression of CK10 and CK17 in 60 normal cervical tissues, 60 cervical intraepithelial neoplasia and 120 cervical cancer tissues. Results:The positive expression of CK10 was located in cytoplasm,and the positive expression rates were 80.00%,50.00%,and 21.67% in normal cervical tissues,CIN,and cervical cancer patients,respectively,showing a significant difference among the three groups(P<0.001).The positive expression of CK17 was located in cytoplasm.The positive expression rates of the three groups were 0%,46.67% and 80.00%,respectively,with significant differences(P<0.001).The χ~2 test analyzed that the expression of CK17 in cervical cancer tissues was independent of FIGO stage,lymph node metastasis,pathological classification and tissue differentiation(P>0.05).The expression of CK10 was independent of the patient's FIGO stage,lymph node metastasis or pathological typing,and was related to the degree of tissue differentiation(P=0.021).Kaplan-Meier survival analysis showed that the 1-year,3-year and 5-year survival rates of patients with early cervical cancer treated by surgery were 100%,96.7% and 93.3%,respectively.The 5-year survival rates in the CK10 negative group and the positive group were 91.5% and 100%,respectively(P>0.05). The 5-year survival rate of the CK17 negative group and the positive group was 100% and 91.7%,respectively(P>0.05).Univariate analysis showed that the expression of CK10 and CK17 was not correlated with prognosis(P>0.05),and age,lymph node metastasis,FIGO stage,tissue differentiation,and pathological classification were significantly correlated with prognosis(P<0.05).According to the expression of CK17 and CK10,we divided the patients into four groups.The 1-year,3-year and 5-year survival rate of CK17 positive CK10 negative group was:100%,94.9%,89.7%.The 5-year survival rate of CK17 positive CK10 positive,CK17 negative CK10 positive group,CK17 negative CK10 negative was 100%,100%,100%(P=0.211),and there was no statistically significant difference.Conclusion:The expression level of CK10 and negatively correlated with cervical lesion severity.CK17 expression level was positively correlated with cervical lesion severity.Both may participate in the development of cervical cancer,but CK17 and CK10 have little value in predicting the prognosis of patients with cervical cancer,but age,whether lymph node metastasis,FIGO staging,tissue differentiation,pathologic classification are the important factors influencing the prognosis of patients.
Objective:To study the expression and prognostic value of CK10 and CK17 in patients undergoing early cervical cancer surgery.Methods:Standard immunohistochemical SP method was used to detect the expression of CK10 and CK17 in 60 normal cervical tissues, 60 cervical intraepithelial neoplasia and 120 cervical cancer tissues. Results:The positive expression of CK10 was located in cytoplasm,and the positive expression rates were 80.00%,50.00%,and 21.67% in normal cervical tissues,CIN,and cervical cancer patients,respectively,showing a significant difference among the three groups(P<0.001).The positive expression of CK17 was located in cytoplasm.The positive expression rates of the three groups were 0%,46.67% and 80.00%,respectively,with significant differences(P<0.001).The χ~2 test analyzed that the expression of CK17 in cervical cancer tissues was independent of FIGO stage,lymph node metastasis,pathological classification and tissue differentiation(P>0.05).The expression of CK10 was independent of the patient's FIGO stage,lymph node metastasis or pathological typing,and was related to the degree of tissue differentiation(P=0.021).Kaplan-Meier survival analysis showed that the 1-year,3-year and 5-year survival rates of patients with early cervical cancer treated by surgery were 100%,96.7% and 93.3%,respectively.The 5-year survival rates in the CK10 negative group and the positive group were 91.5% and 100%,respectively(P>0.05). The 5-year survival rate of the CK17 negative group and the positive group was 100% and 91.7%,respectively(P>0.05).Univariate analysis showed that the expression of CK10 and CK17 was not correlated with prognosis(P>0.05),and age,lymph node metastasis,FIGO stage,tissue differentiation,and pathological classification were significantly correlated with prognosis(P<0.05).According to the expression of CK17 and CK10,we divided the patients into four groups.The 1-year,3-year and 5-year survival rate of CK17 positive CK10 negative group was:100%,94.9%,89.7%.The 5-year survival rate of CK17 positive CK10 positive,CK17 negative CK10 positive group,CK17 negative CK10 negative was 100%,100%,100%(P=0.211),and there was no statistically significant difference.Conclusion:The expression level of CK10 and negatively correlated with cervical lesion severity.CK17 expression level was positively correlated with cervical lesion severity.Both may participate in the development of cervical cancer,but CK17 and CK10 have little value in predicting the prognosis of patients with cervical cancer,but age,whether lymph node metastasis,FIGO staging,tissue differentiation,pathologic classification are the important factors influencing the prognosis of patients.
引文
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[8] Zhang Chao,Yin Bo.Expression and clinical significance of CK18 and CK19 in prostate cancer[J].Modern Oncology,2018,26(05):0737-0740.[张超,殷波.CK18、CK19在前列腺癌中的表达及其临床意义[J].现代肿瘤医学,2018,26(05):0737-0740.]
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[10] Feng YK,Hu GM,Chang J.Expression of cytokeratin 14 and P16 in cervical lesions and its diagnostic significance[J].Tumor Foundation and Clinic,2018,31(3):189-191.[冯怡锟,胡桂明,常佳.细胞角蛋白14和P16在宫颈病变组织中的表达及其诊断意义[J].肿瘤基础与临床,2018,31(3):189-191.]
[11] Liu YY.Expression of cytokeratin CK5/6 and EGFR in breast cancer tissues[J].Clinical Rational Use of Drugs,2018,11(4):130-131.[刘元英.细胞角蛋白CK5/6和EGFR在乳腺癌组织中的表达[J].临床合理用药,2018,11(4):130-131.]
[12] Martens JE,Arends J,Van der Linden PJ,et al.Cytokeratin 17 and p63 are markers of the HPV target cell,the cervical stem cell[J].Anticancer Research,2004,24(2B):771-775.
[13] Mao LJ,Gu YL,Nie MH,et al.Expression of cytokeratin 10,13,14 and 19 in OLP[J].Journal of Clinical Stomatology,2007,23(12):710-712.[毛良军,古亚兰,聂敏海,等.细胞角蛋白10、13、14和19在OLP中的表达研究[J].临床口腔医学杂志,2007,23(12):710-712.]
[14] Carrilho C,Alberto M,Buane L,et al.Keratins 8,10,13,and 17 are useful markers in the diagnosis of human cervix carcinomas[J].Hum Pathol,2004,35(5),546-551.
[15] Smedts F,Ramaekers F,Troyanovsky S,et al.Keratin expression in cervical cancer[J].American Journal of Pathology,1992,141(2):497-511.
[16] Wang WM,Wang JH,Hou HC.Expression and significance of CK17 in cervical intraepithelial neoplasia and cervical cancer[J].Practical Journal of Cancer,2012,27(1):38-40.[王为民,汪建华,侯洪春.CK17在宫颈上皮内瘤变和宫颈癌组织中的表达及意义[J].实用癌症杂志,2012,27(1):38-40.]
[17] Zhang LY,Jiang FX,Gui DQ,et al.Clinical expression and pathological significance of P16,Ki67,CK8 and CK17 in CIN and cervical squamous cell carcinoma[J].Practical Journal of Cancer,2018,33(8):1242-1244.[张力忆,蒋奉希,桂定清,等.p16、Ki67、CK8、CK17在CIN及宫颈鳞癌中的临床表达及病理意义[J].实用癌症杂志,2018,33(8):1242-1244.]
[18] Wang WM.Expression and significance of CK8 and CK17 in cervical intraepithelial neoplasia and cervical cancer[D].Shandong:Taishan Medical University,2010.[王为民.CK8和CK17在宫颈上皮内瘤变和宫颈癌中的表达及意义[D].山东:泰山医学院,2010.]
[19] Smedts F,Ramaekers FC,Hopman AH.CK17 and p16 expression patterns distinguish(atypical)immature squamous metaplasia from high-grade cervical intraepithelial neoplasia[J].Histopathology,2008,52(4):515-516.
[20] Kitamura R,Toyoshima T,Tanaka H,et al.Cytokeratin 17 mRNA as a prognostic marker of oral squamous cell carcinoma[J].Oncology Letters,2017,14:6735-6743.
[2] Escobar L,Shah R,Roa L,et al,Keratin-17 Promotes p27KIP1 nuclear export and degradation and offers potential prognostic utility[J].Tumor and Stem Cell Biology,2015,24:3650-3662.
[3] Jiang T,Zhang X.Expression of cytokeratin 20 in female cystitis glandularis and its correlation with prognosis[J].Journal of Clinical Medicine in Practice,2018,22(15):118-120.[姜涛,张旭.女性腺性膀胱炎中细胞角蛋白20的表达及其与预后的相关性[J].实用临床医药杂志,2018,22(15):118-120.]
[4] Lin S,Wang W.Expression and clinical significance of CK20 and HMGB1 protein in cervical squamous cell carcinoma[J].Labelled Immunoassay and Clinic,2018,24(8):917-920.
[5] Zhang Xinfang,Yang Zhuo,Wang Danbo.Expression and significance of cytokeratin 20 in cervical squamous cell carcinoma[J].Modern Oncology,2015,23(21):3185-3187.[张馨芳,杨卓,王丹波.细胞角蛋白20在宫颈鳞癌中的表达及意义[J].现代肿瘤医学,2015,23(21):3185-3187.]
[6] Zhou SH,Peng WJ,Chen H,et al.Expression and significance of cytokeratin 20 in lymph node micrometastasis of stage Ⅰ and Ⅱ colorectal cancer[J].Chinese General Surgery Literature,2018,12(2):96-99.
[7] BA Coelho,GT Peterle,M Santos,et al.Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma[J].Genetics and Molecular Research,2015,14(4):15123-15132.
[8] Zhang Chao,Yin Bo.Expression and clinical significance of CK18 and CK19 in prostate cancer[J].Modern Oncology,2018,26(05):0737-0740.[张超,殷波.CK18、CK19在前列腺癌中的表达及其临床意义[J].现代肿瘤医学,2018,26(05):0737-0740.]
[9] Pan QW,Chen DK,Pan JJ,et al.Expression and significance of cytokeratin 7,8 and 10/13 in cervical lesions of different grades[J].Modern Practical Medicine,2018,30(2):219-221.[潘蔷薇,陈大可,潘嘉佳,等.细胞角蛋白7、8和10/13在不同级别宫颈病变中的表达及意义[J].现代实用医学,2018,30(2):219-221.]
[10] Feng YK,Hu GM,Chang J.Expression of cytokeratin 14 and P16 in cervical lesions and its diagnostic significance[J].Tumor Foundation and Clinic,2018,31(3):189-191.[冯怡锟,胡桂明,常佳.细胞角蛋白14和P16在宫颈病变组织中的表达及其诊断意义[J].肿瘤基础与临床,2018,31(3):189-191.]
[11] Liu YY.Expression of cytokeratin CK5/6 and EGFR in breast cancer tissues[J].Clinical Rational Use of Drugs,2018,11(4):130-131.[刘元英.细胞角蛋白CK5/6和EGFR在乳腺癌组织中的表达[J].临床合理用药,2018,11(4):130-131.]
[12] Martens JE,Arends J,Van der Linden PJ,et al.Cytokeratin 17 and p63 are markers of the HPV target cell,the cervical stem cell[J].Anticancer Research,2004,24(2B):771-775.
[13] Mao LJ,Gu YL,Nie MH,et al.Expression of cytokeratin 10,13,14 and 19 in OLP[J].Journal of Clinical Stomatology,2007,23(12):710-712.[毛良军,古亚兰,聂敏海,等.细胞角蛋白10、13、14和19在OLP中的表达研究[J].临床口腔医学杂志,2007,23(12):710-712.]
[14] Carrilho C,Alberto M,Buane L,et al.Keratins 8,10,13,and 17 are useful markers in the diagnosis of human cervix carcinomas[J].Hum Pathol,2004,35(5),546-551.
[15] Smedts F,Ramaekers F,Troyanovsky S,et al.Keratin expression in cervical cancer[J].American Journal of Pathology,1992,141(2):497-511.
[16] Wang WM,Wang JH,Hou HC.Expression and significance of CK17 in cervical intraepithelial neoplasia and cervical cancer[J].Practical Journal of Cancer,2012,27(1):38-40.[王为民,汪建华,侯洪春.CK17在宫颈上皮内瘤变和宫颈癌组织中的表达及意义[J].实用癌症杂志,2012,27(1):38-40.]
[17] Zhang LY,Jiang FX,Gui DQ,et al.Clinical expression and pathological significance of P16,Ki67,CK8 and CK17 in CIN and cervical squamous cell carcinoma[J].Practical Journal of Cancer,2018,33(8):1242-1244.[张力忆,蒋奉希,桂定清,等.p16、Ki67、CK8、CK17在CIN及宫颈鳞癌中的临床表达及病理意义[J].实用癌症杂志,2018,33(8):1242-1244.]
[18] Wang WM.Expression and significance of CK8 and CK17 in cervical intraepithelial neoplasia and cervical cancer[D].Shandong:Taishan Medical University,2010.[王为民.CK8和CK17在宫颈上皮内瘤变和宫颈癌中的表达及意义[D].山东:泰山医学院,2010.]
[19] Smedts F,Ramaekers FC,Hopman AH.CK17 and p16 expression patterns distinguish(atypical)immature squamous metaplasia from high-grade cervical intraepithelial neoplasia[J].Histopathology,2008,52(4):515-516.
[20] Kitamura R,Toyoshima T,Tanaka H,et al.Cytokeratin 17 mRNA as a prognostic marker of oral squamous cell carcinoma[J].Oncology Letters,2017,14:6735-6743.