P～（27）、PTEN、PCNA、TTF-1在甲状腺良恶性病变中的表达
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摘要
目的：检测P27、PTEN、PCNA及TTF-1在甲状腺不同病变中的蛋白表达，探讨P27、PTEN、PCNA及TTF-1在甲状腺癌发生发展中的作用及其临床意义。
方法：应用免疫组织化学S—P法检测15例结节性甲状腺肿组织、15例腺瘤、43例甲状腺癌组织中P27、PTEN、PCNA及TTF-1的表达。
结果：免疫组化染色结果表明，结节性甲状腺肿组织P27、PTEN表达的阳性率均为80.0%，癌组织中P27、PTEN表达的阳性率分别为34.9%和46.5%，明显低于结节性甲状腺肿（P<0.01）。PCNA在结节性甲状腺肿阳性表达率为26.7%，癌中阳性率为72.1%，二者有显著统计学差异（P<0.01）。TTF-1在结节性甲状腺肿阳性率为100%，癌组织中为79.1%，在良恶性病变中表达无差异（P>0.05）。P27的表达与甲状腺肿瘤组织学分型密切相关，PTEN、PCNA的表达与淋巴结转移相关（P<0.05）。P27与 PTEN在癌组织中的表达呈正相关，与PCNA呈负相关（P<0.01）。
结论：P27基因失活或蛋白表达降低与甲状腺肿瘤的组织学分型及浸润程度密切相关，且与PTEN呈显著正相关，与PCNA显著负相关，联合检测P27、PTEN、PCNA有助于甲状腺肿瘤的诊断及预后评估。TTF-1在甲状腺常见良恶性病变中阳性率均高，特异地表达在细胞核，是一种特异的甲状腺滤泡细胞标记物。
Objective: To research expression of P27 and PTEN﹑PCNA﹑TTF-1 protein in the different thyroid diseases.To investigate the role and clinical significance of P27﹑PTEN﹑PCNA and TTF-1 in the pathogenesis of thyroid carcinoma.
Methods: The expression of P27﹑PTEN﹑PCNA and TTF-1 were examined immunohistochemically in 15 cases of nodular goiter,15 cases of adenoma and 43 cases of thyroid carcinoma.
Results: Immunohistochemical staining results revealed that when compared with the P27 and PTEN positive rates of nodular goiter tissues(80.0% and 80.0%, respective) the P27 positive rates of thyroid carcinoma(34.9%) and the PTEN positive rates of thyroid carcinoma(46.5%) were significantly lower(P<0.01).In the nodular goiter tissues,the positive rates of expression was 26.7% for PCNA,and that in the thyroid neoplasma was 72.1%.The different expression of PCNA protein in nodular goiter and thyroid neoplasma was very obvious(P<0.01).The positive rates of expression of TTF-1 in nodular goiter tissues was 100%,and that in the thyroid carcinoma was 79.1%,the difference was insignificant between the two types.P27 expression was associated with histological type and infiltrative degree (P<0.05),but P27 expression wasn't associated with lymph node metastasis(P>0.05).The PTEN and PCNA expression were correlated with lymph node metastasis.(P<0.05).The expression of TTF-1 was not correlated with infiltrative degree and lymph node metastasis.There was significant positive correlation between the expression of P27 and PTEN.And negative correlation between P27 and PCNA.
Conclusion: Loss of decreased expression P27 was significantly correlated with differentiation of thyroid carcinoma and infiltrative degree and markedly correlated with the expression of PTEN and PCNA.Combination of P27﹑PTEN and PCNA dection may be a powerful and aid in evaluating prognosis and
infiltrative capability of thyroid carcinoma.TTF-1 was expressed in the majority of benign and malignant thyroid diseases.The immnostaining of TTF-1 was located in nuclear of cells,TTF-1 was a sensitive marker for thyroid follicular cells.
方法：应用免疫组织化学S—P法检测15例结节性甲状腺肿组织、15例腺瘤、43例甲状腺癌组织中P27、PTEN、PCNA及TTF-1的表达。
结果：免疫组化染色结果表明，结节性甲状腺肿组织P27、PTEN表达的阳性率均为80.0%，癌组织中P27、PTEN表达的阳性率分别为34.9%和46.5%，明显低于结节性甲状腺肿（P<0.01）。PCNA在结节性甲状腺肿阳性表达率为26.7%，癌中阳性率为72.1%，二者有显著统计学差异（P<0.01）。TTF-1在结节性甲状腺肿阳性率为100%，癌组织中为79.1%，在良恶性病变中表达无差异（P>0.05）。P27的表达与甲状腺肿瘤组织学分型密切相关，PTEN、PCNA的表达与淋巴结转移相关（P<0.05）。P27与 PTEN在癌组织中的表达呈正相关，与PCNA呈负相关（P<0.01）。
结论：P27基因失活或蛋白表达降低与甲状腺肿瘤的组织学分型及浸润程度密切相关，且与PTEN呈显著正相关，与PCNA显著负相关，联合检测P27、PTEN、PCNA有助于甲状腺肿瘤的诊断及预后评估。TTF-1在甲状腺常见良恶性病变中阳性率均高，特异地表达在细胞核，是一种特异的甲状腺滤泡细胞标记物。
Objective: To research expression of P27 and PTEN﹑PCNA﹑TTF-1 protein in the different thyroid diseases.To investigate the role and clinical significance of P27﹑PTEN﹑PCNA and TTF-1 in the pathogenesis of thyroid carcinoma.
Methods: The expression of P27﹑PTEN﹑PCNA and TTF-1 were examined immunohistochemically in 15 cases of nodular goiter,15 cases of adenoma and 43 cases of thyroid carcinoma.
Results: Immunohistochemical staining results revealed that when compared with the P27 and PTEN positive rates of nodular goiter tissues(80.0% and 80.0%, respective) the P27 positive rates of thyroid carcinoma(34.9%) and the PTEN positive rates of thyroid carcinoma(46.5%) were significantly lower(P<0.01).In the nodular goiter tissues,the positive rates of expression was 26.7% for PCNA,and that in the thyroid neoplasma was 72.1%.The different expression of PCNA protein in nodular goiter and thyroid neoplasma was very obvious(P<0.01).The positive rates of expression of TTF-1 in nodular goiter tissues was 100%,and that in the thyroid carcinoma was 79.1%,the difference was insignificant between the two types.P27 expression was associated with histological type and infiltrative degree (P<0.05),but P27 expression wasn't associated with lymph node metastasis(P>0.05).The PTEN and PCNA expression were correlated with lymph node metastasis.(P<0.05).The expression of TTF-1 was not correlated with infiltrative degree and lymph node metastasis.There was significant positive correlation between the expression of P27 and PTEN.And negative correlation between P27 and PCNA.
Conclusion: Loss of decreased expression P27 was significantly correlated with differentiation of thyroid carcinoma and infiltrative degree and markedly correlated with the expression of PTEN and PCNA.Combination of P27﹑PTEN and PCNA dection may be a powerful and aid in evaluating prognosis and
infiltrative capability of thyroid carcinoma.TTF-1 was expressed in the majority of benign and malignant thyroid diseases.The immnostaining of TTF-1 was located in nuclear of cells,TTF-1 was a sensitive marker for thyroid follicular cells.
引文
Culurman Be, Roberts Jm. Cell cycle and cancer. J National Cancer Institute. 1995,87:1499～1502.
Rao J, Eu Kw,Seow-chien F,et al. Down-regulation of P27 is a significant predictor of poor overall survival and may facilitate metastasis in colorectal carcinomas.Int[J]Cancer,2000,89(3):213～216.
Barbaeschi M, Tinteren HV,Mauri FA, et al. P27 expression in breast carcinomas:an immunohistochemical study on 512 patients with long-term follow up. Int[J]Cancer,2000,89(3):236～241.
Singh S P, Lipman J, Goldman H, et al. Loss and altered subcellular localization of P27 inBarrett's associated adenocarcinoma. Cancer Res,1998,58(8):1730～1735.
Bruni P, Boccia A, Baldassarre G, et al. PTEN expression is reduced in a subset of sporadic thyroid carcinoma: evidence that PTEN–growth suppressing activity in thyroid cancer cells is mediated by P27. Oncogene,2000;19:3146～3155.
庄严，段学宁，王文治等。甲状腺癌VEGF和PCNA表达及相关性研究。中国肿瘤临床，2001，28（6）.443～447.
Shimizu T, Usuda N, Yamanda T,et al. Proliferative activity of human thyroid tumors evaluated by proliferativing cell nuclear antigen/cyclin immunohistochemical studies. Cancer,1993,71:2807.
李君，严丽萍，滕晓东.甲状腺转录因子在甲状腺良恶性病变中的表达。肿瘤学杂志。2003；9（1）：19～20.
Yasui W, Kudo Y, Semba S,et al. Reduced expression of cyclin-dependant kinase inhibitor P27 is associated with advanced stage and invasiveness of gastric carcinomas. Jpn J. Cancer Res,1997,88:625～629.
Kawamata N, Morosetti R, Miller CW, et al. Molecular analysis of the cyclin depend kinase inhibitor gene P27 in human malignanscies. Cancer Res, 1995,55:2266～2269.
Lloyd RV, Jin L, Qian X, et al. Aberrant P27 expression in endocrine and
other tumors. Am J Pathol,1997,150:401～407.
Tan P, Cady B, Wanner M. The cell cycle inhibitor P27 is an independent prognostic marker in small invasive breast carcinoma [J]. Cancer Res, 1997,57(7):1259
Pennisi E. New tumor suppressor found-twece [J]. Science, 1997, 275(5308):1876～1878.
Lin SF, Hsieh MC, Liu TC, et al. Mutation analysis of PTEN/MMAC1 in sporadic thyroid tumors. Kaohsiung J Med Sci 2000 Jan, 16(1):9～12.
Gimm O, Perren A, Weng LP, et al. Am J Pathol. 2000,156(5):1693～1700.
Tolkacheva T, Chan A, Inhibition of H-Ras transformation by the PTEN/MMAC1/TEP1 tumor suppressor gene. Oncogene, 2000,19:680～689.
Picristofano A, De Acetis M, Koff A. PTEN and P27 cooperate in prostate cancer tumor suppression in the mouse[J] Nat Genet. 2001,27(2):222～224.
Kurose K, Zhou XP, Araki T, et al. Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with P27 and cyclinD1 expression in primary epithemal ovarian carcinomas[J].Am J Pathol. 2001,158(6):2097～2106.
Landberg G, Tan EM, Roos G.Flow cytometric multiparameter analysis of proliferating cell nuclear antigen and Ki-67 antigen. Exp Cell Res. 1990,187:111～118.
陈燕昌，陈大良，殷凤峙。增殖细胞核抗原在甲状腺癌中的表达及其意义。实用癌症杂志。1997，12（3）：169～171.
杨燕初，卓建红，谢群。甲状腺癌P21、P53、PCNA表达及其意义。广西医学.1999，21（5）：853～855.
孙海燕。增殖细胞核抗原的特性及应用。实用癌症杂志.2002，17（1）：105～106.
Bejarano PA, Baughrnan RP, Biddinger PW, et al. Surgactant proteins and
thyroid transcription factor-1 in pulmonary and breast carcinomas[J]. Mod Pathol. 1996. 9445～9452.
Fabio P, Fabio B, Damante G, et al. Prognostic value of thyroid transcription factor-1 in primary resected non-small cell lung carcinoma[J]. Mod Pathol, 1999,12:318～324.
陈云，朱明华，周晓军等。甲状腺转录因子-1在滤泡源性甲状腺肿瘤中的表达及其与RET等3种基因表达的相关性研究。中华医学杂志。2002，82（4）：257～261.
Rao J, Eu Kw,Seow-chien F,et al. Down-regulation of P27 is a significant predictor of poor overall survival and may facilitate metastasis in colorectal carcinomas.Int[J]Cancer,2000,89(3):213～216.
Barbaeschi M, Tinteren HV,Mauri FA, et al. P27 expression in breast carcinomas:an immunohistochemical study on 512 patients with long-term follow up. Int[J]Cancer,2000,89(3):236～241.
Singh S P, Lipman J, Goldman H, et al. Loss and altered subcellular localization of P27 inBarrett's associated adenocarcinoma. Cancer Res,1998,58(8):1730～1735.
Bruni P, Boccia A, Baldassarre G, et al. PTEN expression is reduced in a subset of sporadic thyroid carcinoma: evidence that PTEN–growth suppressing activity in thyroid cancer cells is mediated by P27. Oncogene,2000;19:3146～3155.
庄严，段学宁，王文治等。甲状腺癌VEGF和PCNA表达及相关性研究。中国肿瘤临床，2001，28（6）.443～447.
Shimizu T, Usuda N, Yamanda T,et al. Proliferative activity of human thyroid tumors evaluated by proliferativing cell nuclear antigen/cyclin immunohistochemical studies. Cancer,1993,71:2807.
李君，严丽萍，滕晓东.甲状腺转录因子在甲状腺良恶性病变中的表达。肿瘤学杂志。2003；9（1）：19～20.
Yasui W, Kudo Y, Semba S,et al. Reduced expression of cyclin-dependant kinase inhibitor P27 is associated with advanced stage and invasiveness of gastric carcinomas. Jpn J. Cancer Res,1997,88:625～629.
Kawamata N, Morosetti R, Miller CW, et al. Molecular analysis of the cyclin depend kinase inhibitor gene P27 in human malignanscies. Cancer Res, 1995,55:2266～2269.
Lloyd RV, Jin L, Qian X, et al. Aberrant P27 expression in endocrine and
other tumors. Am J Pathol,1997,150:401～407.
Tan P, Cady B, Wanner M. The cell cycle inhibitor P27 is an independent prognostic marker in small invasive breast carcinoma [J]. Cancer Res, 1997,57(7):1259
Pennisi E. New tumor suppressor found-twece [J]. Science, 1997, 275(5308):1876～1878.
Lin SF, Hsieh MC, Liu TC, et al. Mutation analysis of PTEN/MMAC1 in sporadic thyroid tumors. Kaohsiung J Med Sci 2000 Jan, 16(1):9～12.
Gimm O, Perren A, Weng LP, et al. Am J Pathol. 2000,156(5):1693～1700.
Tolkacheva T, Chan A, Inhibition of H-Ras transformation by the PTEN/MMAC1/TEP1 tumor suppressor gene. Oncogene, 2000,19:680～689.
Picristofano A, De Acetis M, Koff A. PTEN and P27 cooperate in prostate cancer tumor suppression in the mouse[J] Nat Genet. 2001,27(2):222～224.
Kurose K, Zhou XP, Araki T, et al. Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with P27 and cyclinD1 expression in primary epithemal ovarian carcinomas[J].Am J Pathol. 2001,158(6):2097～2106.
Landberg G, Tan EM, Roos G.Flow cytometric multiparameter analysis of proliferating cell nuclear antigen and Ki-67 antigen. Exp Cell Res. 1990,187:111～118.
陈燕昌，陈大良，殷凤峙。增殖细胞核抗原在甲状腺癌中的表达及其意义。实用癌症杂志。1997，12（3）：169～171.
杨燕初，卓建红，谢群。甲状腺癌P21、P53、PCNA表达及其意义。广西医学.1999，21（5）：853～855.
孙海燕。增殖细胞核抗原的特性及应用。实用癌症杂志.2002，17（1）：105～106.
Bejarano PA, Baughrnan RP, Biddinger PW, et al. Surgactant proteins and
thyroid transcription factor-1 in pulmonary and breast carcinomas[J]. Mod Pathol. 1996. 9445～9452.
Fabio P, Fabio B, Damante G, et al. Prognostic value of thyroid transcription factor-1 in primary resected non-small cell lung carcinoma[J]. Mod Pathol, 1999,12:318～324.
陈云，朱明华，周晓军等。甲状腺转录因子-1在滤泡源性甲状腺肿瘤中的表达及其与RET等3种基因表达的相关性研究。中华医学杂志。2002，82（4）：257～261.