p16INK4a蛋白在胸腹水细胞蜡块中的表达及临床意义
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摘要
目的检测p16INK4a蛋白在胸腹水细胞蜡块中的表达水平,并探讨其临床意义。方法胸腹水细胞蜡块标本77例,其中恶性60例,良性17例,通过免疫组化的方法检测p16INK4a蛋白在其中的表达水平。结果在恶性胸腹水样本中,p16INK4a蛋白阳性(染色强度≥++)表达率高达83.33%,p16INK4a阴性表达率为16.67%,与良性病变相比较差异具有统计学意义(P<0.05)。以p16INK4a中等染色强度(≥++)为界值,p16INK4a作为恶性肿瘤分子标志的敏感性为75.76%、特异性为64.29%、阳性预测值为83.33%、阴性预测值为52.94%;同时,p16INK4a在肺癌胸腹水样本中的敏感性为76.47%、特异性为69.23%、阳性预测值为86.67%、阴性预测值为52.94%,在其他恶性肿瘤胸腹水样本中的敏感性为75.00%、特异性为60.00%、阳性预测值为80.00%、阴性预测值为52.94%,二者差异无统计学意义(P>0.05)。结论 p16INK4a蛋白代偿性高表达是恶性胸腹水的免疫表型特征,可作为肿瘤分子靶标,适合用于良恶性胸腹水的诊断和鉴别诊断,有助于提高恶性胸腹水的阳性检出率。
Objective To investigate the expression and its clinical significance of p16 INK4 a protein in paraffin-embedded specimens from ascites and pleural effusion.Methods Totally 77 cases of paraffin-embedded specimens from ascites and pleural effusion were collected,including 60 malignant tumor cases and 17 benign lesion cases.The expression of p16 INK4 a was detected by immunohistochemistry(IHC).Results In malignant tumor cases,the positive rate of p16 INK4 a expression(≥ + +) was 83.33%,significantly higher than that in benign lesion cases(P < 0.05).Using p16 INK4 a medium staining intensity(≥ + +) as the boundary value of positive expression,the sensitivity,specificity,positive predictive value(PPV) and negative predictive value(NPV) of p16 INK4 a as a biomarker for malignant tumor were 75.76%,64.29%,83.33% and 52.94%,respectively.The sensitivity,specificity,PPV and NPV of p16 INK4 a were 76.47%,69.23%,86.67% and 52.94% for lung carcinoma,respectively,and 75.00%,60.00%,80.00%and 52.94% for the other kinds of malignant tumors.The results showed that there was no statistical difference in the clinical significance of p16 INK4 a between lung carcinoma and the other kinds of malignant tumor(P > 0.05).Conclusion The compensatory high expression of p16 INK4 a is an important immunophenotypic characteristic of malignant tumor cells in ascites and pleural effusion.So p16 INK4 a could be used as a biomarker to differentially diagnose the malignant and benign ascites and pleural effusion,and helps to improve the positive detection rate of malignant pleural effusion and ascites.
Objective To investigate the expression and its clinical significance of p16 INK4 a protein in paraffin-embedded specimens from ascites and pleural effusion.Methods Totally 77 cases of paraffin-embedded specimens from ascites and pleural effusion were collected,including 60 malignant tumor cases and 17 benign lesion cases.The expression of p16 INK4 a was detected by immunohistochemistry(IHC).Results In malignant tumor cases,the positive rate of p16 INK4 a expression(≥ + +) was 83.33%,significantly higher than that in benign lesion cases(P < 0.05).Using p16 INK4 a medium staining intensity(≥ + +) as the boundary value of positive expression,the sensitivity,specificity,positive predictive value(PPV) and negative predictive value(NPV) of p16 INK4 a as a biomarker for malignant tumor were 75.76%,64.29%,83.33% and 52.94%,respectively.The sensitivity,specificity,PPV and NPV of p16 INK4 a were 76.47%,69.23%,86.67% and 52.94% for lung carcinoma,respectively,and 75.00%,60.00%,80.00%and 52.94% for the other kinds of malignant tumors.The results showed that there was no statistical difference in the clinical significance of p16 INK4 a between lung carcinoma and the other kinds of malignant tumor(P > 0.05).Conclusion The compensatory high expression of p16 INK4 a is an important immunophenotypic characteristic of malignant tumor cells in ascites and pleural effusion.So p16 INK4 a could be used as a biomarker to differentially diagnose the malignant and benign ascites and pleural effusion,and helps to improve the positive detection rate of malignant pleural effusion and ascites.
引文
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[12]付冉,王艳林,黄利鸣.p16表达异常与肿瘤关系的研究进展[J].生命的化学,2017,37(4):585-589.
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[14]Al-Ansari MM,Hendrayani SF,Shehata AI.P16(INK4A)represses the paracrine tumor-promoting effects of breast stromal fibroblasts[J].Oncogene,2013,32(18):2356-2364.
[15]Lim HK,Park JM,Chi KC,et al.Disappearance of serum methylated p16 indicates longer survival in patients with gastric cancer[J].J Gastric Cancer,2013,13(3):157-163.
[16]Sritippho T,Chotjumlong P,Iamaroon A.Roles of human papillomaviruses and p16 in oral cancer[J].Asian Pac J Cancer Prevent,2015,16(15):6193-6200.
[17]Chang Z,Ju H,Ling J,et al.Cooperativity of oncogenic K-ras and downregulated p16/INK4A in human pancreatic tumorigenesis[J].PLos One,2014,9(7):e101452.
[18]Burdelski C,Dieckmann T,Heumann A,et al.p16 upregulation is linked to poor prognosis in ERG negative prostate cancer[J].Tumour Biol,2016,37(9):1-9.
[19]Yoon N,Yoon G,Park CK,et al.Stromal p16 expression is significantly increased in malignant ovarian neoplasms[J].Oncotarget,2016,7(40):64665-64673.
[20]Yoruker EE,Mert U,Bugra D,et al.Promoter and histone methylation and p16(INK4A)gene expression in colon cancer[J].Exp Therap Med,2012,4(5):865-870.
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[22]刘玉艳,沈久洋,朱安超,等.P16/Ki67细胞学双染在子宫颈癌筛查中应用价值[J].临床与实验病理学杂志,2017,33(1):38-40.
[23]丁莉,邹先进,郑杰,等.两种筛查宫颈肿瘤方法的比较:ELISA检测宫颈脱落细胞p16INK4a蛋白FQ-PCR检测8种共用型HPV DNA[J].现代妇产科进展,2010,19(1):37-40.
[24]乐桂花.P16与Ki67的表达在子宫颈病变诊断中的应用[J].中外医疗,2016,35(10):46-48.
[25]黄小钟,郭睿,黄莺,等.p16INK4a蛋白在结直肠癌中表达及临床意义[J].中华实用诊断与治疗杂志,2016,30(12):1227-1229.
[26]杨军,黄小钟,郭睿,等.p16INK4a蛋白可作为乳腺癌特异性分子标志[J].南方医科大学学报,2016,36(6):751-755.
[27]王书奎.精准检测之肿瘤标志物研究进展[J].标记免疫分析与临床,2016,23(10):1113-1118.
[28]Martin N,Popov N,Aguilo F,et al.Interplay between homeobox proteins and polycomb repressive complexes in p16INK4a regulation[J].EMBO J,2013,32(7):982-995.
[2]黄金长,张功亮,郭广秀,等.细胞块石蜡包埋及免疫细胞化学染色技术在胸腹水细胞病理学诊断中的应用价值[J].实验与检验医学,2013,31(5):489-490.
[3]李琳,胡海,黄晓楠.胸腹水沉淀物制片方法介绍[J].诊断病理学杂志,2003,10(1):50-50.
[4]Travis J.Closing in on melanoma susceptibility gene(s)[J].Science,1992,258(5085):1080-1081.
[5]Serrano M,Hannon GJ,Beach D.A new regulatory motif in cellcycle control causing specific inhibition of cyclin D/CDK4[J].Nature,1993,366(6456):704-707.
[6]Ma J,He X,Wang W,et al.E2F promoter-regulated oncolytic adenovirus with p16 gene induces cell apoptosis and exerts antitumor effect on gastric cancer[J].Dig Dis Sci,2009,54(7):1425-1431.
[7]杨军,康安静,苏宝山,等.免疫组织化学检测结果判读进展[J].中华临床医师杂志:电子版,2014,8(20):3699-3703.
[8]Zhao R,Bu YC,Lee MH,et al.Implications of genetic and epigenetic alterations of CDKN2A(p16INK4a)in cancer[J].Ebiomedicine,2016,8(c):30-39.
[9]Fujiwaraigarashi A,Gotokoshino Y,Mochizuki H,et al.Inhibition of p16 tumor suppressor gene expression via promoter hypermethylation in canine lymphoid tumor cells[J].Res Vet Sci,2014,97(1):60-63.
[10]Lee JJ,Ko E,Cho J,et al.Methylation and immunoexpression of p16(INK4a)tumor suppressor gene in primary breast cancer tissue and their quantitative p16(INK4a)hypermethylation in plasma by real-time PCR[J].Korean J Pathol,2012,46(6):554-561.
[11]Johansson C,Somberg M,Li X,et al.HPV-16 E2 contributes to induction of HPV-P16 late gene expression by inhibiting early polyadenylation[J].EMBO J,2012,31(14):3212-3227.
[12]付冉,王艳林,黄利鸣.p16表达异常与肿瘤关系的研究进展[J].生命的化学,2017,37(4):585-589.
[13]Chen JL,Chen JR,Huang FF,et al.Analysis of p16 gene mutations and their expression using exhaled breath condensate in non-small-cell lung cancer[J].Oncol Lett,2015,10(3):1477-1480.
[14]Al-Ansari MM,Hendrayani SF,Shehata AI.P16(INK4A)represses the paracrine tumor-promoting effects of breast stromal fibroblasts[J].Oncogene,2013,32(18):2356-2364.
[15]Lim HK,Park JM,Chi KC,et al.Disappearance of serum methylated p16 indicates longer survival in patients with gastric cancer[J].J Gastric Cancer,2013,13(3):157-163.
[16]Sritippho T,Chotjumlong P,Iamaroon A.Roles of human papillomaviruses and p16 in oral cancer[J].Asian Pac J Cancer Prevent,2015,16(15):6193-6200.
[17]Chang Z,Ju H,Ling J,et al.Cooperativity of oncogenic K-ras and downregulated p16/INK4A in human pancreatic tumorigenesis[J].PLos One,2014,9(7):e101452.
[18]Burdelski C,Dieckmann T,Heumann A,et al.p16 upregulation is linked to poor prognosis in ERG negative prostate cancer[J].Tumour Biol,2016,37(9):1-9.
[19]Yoon N,Yoon G,Park CK,et al.Stromal p16 expression is significantly increased in malignant ovarian neoplasms[J].Oncotarget,2016,7(40):64665-64673.
[20]Yoruker EE,Mert U,Bugra D,et al.Promoter and histone methylation and p16(INK4A)gene expression in colon cancer[J].Exp Therap Med,2012,4(5):865-870.
[21]Tada T,Watanabe T,Kazama S,et al.Reduced p16 expression correlates with lymphatic invasion in colorectal cancers[J].Hepatogastroenterology,2003,50(54):1756-1760.
[22]刘玉艳,沈久洋,朱安超,等.P16/Ki67细胞学双染在子宫颈癌筛查中应用价值[J].临床与实验病理学杂志,2017,33(1):38-40.
[23]丁莉,邹先进,郑杰,等.两种筛查宫颈肿瘤方法的比较:ELISA检测宫颈脱落细胞p16INK4a蛋白FQ-PCR检测8种共用型HPV DNA[J].现代妇产科进展,2010,19(1):37-40.
[24]乐桂花.P16与Ki67的表达在子宫颈病变诊断中的应用[J].中外医疗,2016,35(10):46-48.
[25]黄小钟,郭睿,黄莺,等.p16INK4a蛋白在结直肠癌中表达及临床意义[J].中华实用诊断与治疗杂志,2016,30(12):1227-1229.
[26]杨军,黄小钟,郭睿,等.p16INK4a蛋白可作为乳腺癌特异性分子标志[J].南方医科大学学报,2016,36(6):751-755.
[27]王书奎.精准检测之肿瘤标志物研究进展[J].标记免疫分析与临床,2016,23(10):1113-1118.
[28]Martin N,Popov N,Aguilo F,et al.Interplay between homeobox proteins and polycomb repressive complexes in p16INK4a regulation[J].EMBO J,2013,32(7):982-995.
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