p16INK4a蛋白在人恶性肿瘤组织中的表达及临床意义
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摘要
目的探讨p16INK4a蛋白在多种人恶性肿瘤组织中的表达及临床意义。方法收集2014年至2015年手术切除的肿瘤标本642例。免疫组化染色检测并分析p16INK4在肿瘤组织中的表达。结果 642例肿瘤样本中良性肿瘤120例、恶性肿瘤522例。免疫组化检测p16INK4a在恶性肿瘤组织中表达阴性(-)、弱阳性(+)、中等阳性(++)和强阳性(+++)表达率分别为17.43%(91/522)、11.11%(58/522)、19.16%(100/522)和52.30%(273/522),而在良性病变中表达率分别为34.17%(41/120)、23.33%(28/120)、26.67%(32/120)和15.83%(19/120),差异具有统计学意义(P<0.05)。在不同组织来源的肿瘤中p16INK4a蛋白阳性表达率也并不相同(P<0.05)。分别以阳性免疫组化染色"++"和"+++"作为p16INK4A阳性表达界值,则p16INK4A蛋白作为恶性肿瘤分子标志的灵敏度、特异度和阳性预测值分别为71.46%、57.50%、87.97%和52.30%、84.17%和93.49%。结论 p16INK4A代偿性高表达是人恶性肿瘤特异性的免疫表型,可作为恶性肿瘤诊断、鉴别诊断和分子分型的分子标志。
Objective To investigate the expression of p16 INK4 a protein in human cancers and analyze its clinical significance. Methods A total of 642 cases surgical specimens of primary human tumors from 2014 to 2015 were underwent operations in the study. Immunohistochemical staining was used to detect and analyze the expression of p16 INK4 in tumor tissues. Results Of the 642 tumor samples,120 were benign and 522 were malignant. The expression rates of p16 INK4 a negative(-),weak positive( +),moderately positive( ++) and strong positive( + + +) were 17. 43%( 91/522),11. 11%( 58/522),19. 16%( 100/522) and 52. 30%( 273/522) in malignant tumor tissues,respectively; while in benign lesions,the expression rates were 34. 17%( 41/120),23. 33%( 28/120),26. 67%( 32/120) and 15. 83%( 19/120),respectively. The difference was statistically significant( P<0. 05). The positive expression rate of p16 INK4 a protein in different tissues derived tumors was not the same( P<0. 05).Using p16 INK4 a protein as a biological molecules marker of malignant tumor,the sensitivity and specificity and positive predictive value of it were different as choosing different positive cell value. While using moderately positive as positive value,the sensitivity,specificity and positive predictive value were 71. 46%,57. 50% and 87. 97%. While using strong positive as positive value,the sensitivity,specificity and positive predictive value were 52. 30%,84. 17% and 93. 49%. Conclusion The compensatory high expression of p16 INK4 A is a tumor specific immune phenotype,which is related to the abnormal cell cycle patterns of tumor,and can be used as a molecular marker for the diagnosis,differential diagnosis and molecular typing of malignant tumors.
Objective To investigate the expression of p16 INK4 a protein in human cancers and analyze its clinical significance. Methods A total of 642 cases surgical specimens of primary human tumors from 2014 to 2015 were underwent operations in the study. Immunohistochemical staining was used to detect and analyze the expression of p16 INK4 in tumor tissues. Results Of the 642 tumor samples,120 were benign and 522 were malignant. The expression rates of p16 INK4 a negative(-),weak positive( +),moderately positive( ++) and strong positive( + + +) were 17. 43%( 91/522),11. 11%( 58/522),19. 16%( 100/522) and 52. 30%( 273/522) in malignant tumor tissues,respectively; while in benign lesions,the expression rates were 34. 17%( 41/120),23. 33%( 28/120),26. 67%( 32/120) and 15. 83%( 19/120),respectively. The difference was statistically significant( P<0. 05). The positive expression rate of p16 INK4 a protein in different tissues derived tumors was not the same( P<0. 05).Using p16 INK4 a protein as a biological molecules marker of malignant tumor,the sensitivity and specificity and positive predictive value of it were different as choosing different positive cell value. While using moderately positive as positive value,the sensitivity,specificity and positive predictive value were 71. 46%,57. 50% and 87. 97%. While using strong positive as positive value,the sensitivity,specificity and positive predictive value were 52. 30%,84. 17% and 93. 49%. Conclusion The compensatory high expression of p16 INK4 A is a tumor specific immune phenotype,which is related to the abnormal cell cycle patterns of tumor,and can be used as a molecular marker for the diagnosis,differential diagnosis and molecular typing of malignant tumors.
引文
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[14]Mahajan A.Practical issues in the application of p16 immunohistochemistry in diagnostic pathology[J].Human Pathol,2016,51:64-74.
[15]Righi A,Gambarotti M,Sbaraglia M,et al.P16 expression as a prognostic and predictive marker in high grade localized osteosarcoma of the extremities:An analysis of 357 cases[J].Human Pathol,2016,58:15-23.
[2]Zhao R,Choi BY,Lee MH,et al.Implications of genetic and epigenetic alterations of CDKN2A(p16INK4a)in cancer[J].Ebio Med,2016,8(C):30-39.
[3]Marcos M.Cyclin-dependent kinases[J].Genome Biol,2014,15(6):122-122.
[4]Bezerra SM,Chaux A,Ball MW,et al.Human papillomavirus infection and immunohistochemical p16(INK4a)expression as predictors of outcome in penile squamous cell carcinomas[J].Hum Pathol,2015,46(4):532-540.
[5]Wright TC Jr,Behrens CM,Ranger-Moore J,et al.Triaging HPV-positive women with p16/Ki-67 dual-stained cytology:Results from a sub-study nested into the ATHENA trial[J].Gynecol Oncol,2017,144(1):51-56.
[6]杨军,康安静,苏宝山,等.免疫组织化学检测结果判读进展[J/CD].中华临床医师杂志(电子版),2014,8(20):3699-3703.
[7]Peurala E,Koivunen P,Haapasaari KM,et al.The prognostic significance and value of cyclin D1,CDK4 and p16 in human breast cancer[J].Breast Cancer Res,2013,15(1):R5.
[8]Wu N,Jia D,Ibrahim AH,et al.NFIB overexpression cooperates with Rb/p53 deletion to promote small cell lung cancer[J].Oncotarget,2016,7(36):57514-57524.
[9]Choi S,Kim HR,Sung CO,et al.Genomic alterations in the RB pathway indicate prognostic outcomes of early-stage lung adenocarcinoma[J].Clin Cancer Res,2015,21(11):2613-2623.
[10]Hall BM,Balan V,Gleiberman AS,et al.Aging of mice is associated with p16(Ink4a)-andβ-galactosidase-positive macrophage accumulation that can be induced in young mice by senescent cells[J].Aging(Albany NY),2016,8(7):1294-1315.
[11]Sznurkowski J J,awrocki A,Biernat W.The overexpression of p16 is not a surrogate marker for high-risk human papilloma virus genotypes and predicts clinical outcomes for vulvar cancer[J].BMC Cancer,2016,16(1):465.
[12]Meshman J,Wang PC,Chin R,et al.Prognostic significance of p16 in squamous cell carcinoma of the larynx and hypopharynx[J].Am J Otolaryngol,2017,38(1):31-37.
[13]Uguen A,Talagas M,Costa S,et al.A p16-Ki-67-HMB45 immunohistochemistry scoring system as an ancillary diagnostic tool in the diagnosis of melanoma[J].Diagn Pathol,2015,10(1):195.
[14]Mahajan A.Practical issues in the application of p16 immunohistochemistry in diagnostic pathology[J].Human Pathol,2016,51:64-74.
[15]Righi A,Gambarotti M,Sbaraglia M,et al.P16 expression as a prognostic and predictive marker in high grade localized osteosarcoma of the extremities:An analysis of 357 cases[J].Human Pathol,2016,58:15-23.
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