p63、p73在外阴鳞癌中的表达及临床意义
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摘要
目的：
观察p63、p73蛋白在外阴鳞状上皮细胞癌中的表达情况,探讨p63、p73蛋白在外阴鳞状上皮细胞癌发生发展中的作用。方法：
应用免疫组化技术检测p63、p73蛋白在20例正常外阴组织,30例外阴上皮内瘤变组织以及44例外阴鳞状上皮细胞癌组织中的表达水平。
结果：
1.p63蛋白在正常外阴组织,外阴上皮内瘤变组织及外阴鳞癌组织中均可表达。外阴上皮内瘤变组织p63蛋白阳性表达率显著高于正常外阴组织p63蛋白阳性表达率(P<0.05)；外阴鳞癌组织p63蛋白阳性表达率明显高于外阴上皮内瘤变组织p63蛋白阳性表达率(P<0.05)。
2.p63表达与手术病理分期和腹股沟淋巴结转移情况有关,与患者年龄、肿瘤位置、组织学分级等临床病理特征无关。
3.p63表达与外阴鳞癌不良预后相关,p63低表达阳性组累积3年总生存率高于p63高表达阳性组(p<0.05)。
4.p73蛋白在正常外阴组织,外阴上皮内瘤变组织和外阴鳞癌组织中均可表达；外阴上皮内瘤变组织p73蛋白阳性表达率显著高于正常外阴组织p73蛋白阳性表达率(P<0.05)；外阴鳞癌组织p73蛋白阳性表达率明显高于外阴上皮内瘤变组织p73蛋白阳性表达率(P<0.05)。
5.p73表达与腹股沟淋巴结转移情况有关,与患者年龄、肿瘤位置、手术病理分期、组织学分级等临床病理特征无关。
6.相关性分析显示：p63和p73蛋白在外阴鳞癌中的表达呈正相关(rs=0.438,P=0.03)。
结论：
在外阴鳞癌中,p63、p73蛋白表达均明显增强。两者异常表达与外阴鳞癌恶性生物学行为密切相关,p63和p73共同参与外阴鳞癌发生发展。p63异常表达与外阴鳞癌不良预后相关,可以做为外阴鳞癌预后的观察指标。
Objective:
To investigate the expression of p63 and p73 protein in human vulvar squamous cell carcinoma, to explore the role of p63 and p73 in the tumorigenesis and progression of human vulvar squamous cell carcinoma.
Methods:
The expression of p63 and p73 were detected by immunohistochemistry in 20 normal vulvar tissuses,30 vulvar intraepithelial neoplasias and 44 human vulvar squamous cell carcinomas.
Results:
1. p63 protein was detected in normal vuluar tissue, vulvar intraepithelial neoplasia and human vulvar squamous cell carcinoma. The rate of p63 protein expression in vulvar intraepithelial neoplasia was considerably higher than that in normal vulvar tissuse (P<0.05). The positive expression rate for p63 protein in human vulvar squamous cell carcinoma was so much higher than that in vulvar intraepithelial neoplasia (P<0.05).
2. The level expression of p63 was relevant with tumor staging and lymphatic metastasis of vulvar squamous cell carcinoma, while the expression of p63 had no relationship with age, localization and Pathological grading.
3. The abnormal expression of p63 protein was associated with the poor prognosis of vulvar squamous cell carcinoma. The 3-year survival rate for the low expression of p63-Postive was higher than that of the high expression of p63-Postive (p<0.05).
3. p73 protein was detected in normal vuluar tissue, vulvar intraepithelial neoplasia as well as human vulvar squamous cell carcinoma. The rate of p73 protein expression in vulvar intraepithelial neoplasia was higher than that in normal vulvar tissuse (P<0.05). The positive expression rate for p73 protein in human vulvar squamous cell carcinoma was much higher than that in vulvar intraepithelial neoplasia(P<0.05).
4. The expression of p73 correlated with lymphatic node metastasis, while the expression of p73 had no relationship with age, localization, Pathological grading and tumor staging in vulvar squamous cell carcinoma.
5.There was a positive correlation between p63 and p73 protein in vulvar squamous cell carcinoma.
Conclusions:
The expression p63 and p73 protein are increasing in vulvar squamous cell carcinoma. Their abnormal expression maybe associated with malignant biologial behavior. p63 and p73 have dependent fuction in generation, development and invasion of vulvar squamous cell carcinoma. Furthermore, the expression of p63 may provide useful prognosis implication and be an useful prognosis maker for vulvar squamous cell carcinoma.
观察p63、p73蛋白在外阴鳞状上皮细胞癌中的表达情况,探讨p63、p73蛋白在外阴鳞状上皮细胞癌发生发展中的作用。方法：
应用免疫组化技术检测p63、p73蛋白在20例正常外阴组织,30例外阴上皮内瘤变组织以及44例外阴鳞状上皮细胞癌组织中的表达水平。
结果：
1.p63蛋白在正常外阴组织,外阴上皮内瘤变组织及外阴鳞癌组织中均可表达。外阴上皮内瘤变组织p63蛋白阳性表达率显著高于正常外阴组织p63蛋白阳性表达率(P<0.05)；外阴鳞癌组织p63蛋白阳性表达率明显高于外阴上皮内瘤变组织p63蛋白阳性表达率(P<0.05)。
2.p63表达与手术病理分期和腹股沟淋巴结转移情况有关,与患者年龄、肿瘤位置、组织学分级等临床病理特征无关。
3.p63表达与外阴鳞癌不良预后相关,p63低表达阳性组累积3年总生存率高于p63高表达阳性组(p<0.05)。
4.p73蛋白在正常外阴组织,外阴上皮内瘤变组织和外阴鳞癌组织中均可表达；外阴上皮内瘤变组织p73蛋白阳性表达率显著高于正常外阴组织p73蛋白阳性表达率(P<0.05)；外阴鳞癌组织p73蛋白阳性表达率明显高于外阴上皮内瘤变组织p73蛋白阳性表达率(P<0.05)。
5.p73表达与腹股沟淋巴结转移情况有关,与患者年龄、肿瘤位置、手术病理分期、组织学分级等临床病理特征无关。
6.相关性分析显示：p63和p73蛋白在外阴鳞癌中的表达呈正相关(rs=0.438,P=0.03)。
结论：
在外阴鳞癌中,p63、p73蛋白表达均明显增强。两者异常表达与外阴鳞癌恶性生物学行为密切相关,p63和p73共同参与外阴鳞癌发生发展。p63异常表达与外阴鳞癌不良预后相关,可以做为外阴鳞癌预后的观察指标。
Objective:
To investigate the expression of p63 and p73 protein in human vulvar squamous cell carcinoma, to explore the role of p63 and p73 in the tumorigenesis and progression of human vulvar squamous cell carcinoma.
Methods:
The expression of p63 and p73 were detected by immunohistochemistry in 20 normal vulvar tissuses,30 vulvar intraepithelial neoplasias and 44 human vulvar squamous cell carcinomas.
Results:
1. p63 protein was detected in normal vuluar tissue, vulvar intraepithelial neoplasia and human vulvar squamous cell carcinoma. The rate of p63 protein expression in vulvar intraepithelial neoplasia was considerably higher than that in normal vulvar tissuse (P<0.05). The positive expression rate for p63 protein in human vulvar squamous cell carcinoma was so much higher than that in vulvar intraepithelial neoplasia (P<0.05).
2. The level expression of p63 was relevant with tumor staging and lymphatic metastasis of vulvar squamous cell carcinoma, while the expression of p63 had no relationship with age, localization and Pathological grading.
3. The abnormal expression of p63 protein was associated with the poor prognosis of vulvar squamous cell carcinoma. The 3-year survival rate for the low expression of p63-Postive was higher than that of the high expression of p63-Postive (p<0.05).
3. p73 protein was detected in normal vuluar tissue, vulvar intraepithelial neoplasia as well as human vulvar squamous cell carcinoma. The rate of p73 protein expression in vulvar intraepithelial neoplasia was higher than that in normal vulvar tissuse (P<0.05). The positive expression rate for p73 protein in human vulvar squamous cell carcinoma was much higher than that in vulvar intraepithelial neoplasia(P<0.05).
4. The expression of p73 correlated with lymphatic node metastasis, while the expression of p73 had no relationship with age, localization, Pathological grading and tumor staging in vulvar squamous cell carcinoma.
5.There was a positive correlation between p63 and p73 protein in vulvar squamous cell carcinoma.
Conclusions:
The expression p63 and p73 protein are increasing in vulvar squamous cell carcinoma. Their abnormal expression maybe associated with malignant biologial behavior. p63 and p73 have dependent fuction in generation, development and invasion of vulvar squamous cell carcinoma. Furthermore, the expression of p63 may provide useful prognosis implication and be an useful prognosis maker for vulvar squamous cell carcinoma.
引文
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[1]Schmal E H, Bamberger C. A novel protein wit h strong homology to the tumor suppressor p53. Oncogene,1997, Vol.15(11):1363～1367
[2]Yanggy A, Kaghad M, Wang Y, et al. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell, 1998, Vol.2 (3):305～316
[3]Marina Mangiulli, Alessio Valletti, Mariano Francesco Caratozzolo, et al. Identification and functional characterization of two new transcriptional variants of the human p63 gene. Nucleic Acids Research,2009, Vol.37(18):6092～6104
[4]Lu P, Barad M, Vize PD, et al. p63 expression in early ectoderm and neurectoderm. Mech, 2001, Vol.102(1-2):275～278.
[5]王帅,薛永来,冯喜增.p63基因的结构与功能生命科学.生命科学,2007,19(4)：446～450
[6]A. Yang, R. Schweitzer, D. Sun, et al, p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development, Nature,1999, Vol.398:714～718
[7]Mills A.A., Zheng B., Wang X.J., et al, p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature,1999, Vol.398:708～713
[8]Osada M,Kawahara C, et al. Cloning and funcitional analysis of human p51, which stiucturally and functionally resembles p53[J].Nat, Med,1998, Vol.4 (7):839～843.
[9]Weber A, Langhankil L, Schutz A, et al. Expression profiles of p53, p63, and p73 in benign salivary glan tumors. Virchows Arch,2002, Vol.441:428～436
[10]Yang AJ, Kaghad M, W ang Y, et al. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death inducing, and dominantnegative. Mol cell,1998, Vol. 2(3):305～316
[11]Maranke I, Kostera, Dennis R, et al. The role of p63 in development and differentiation of the epidermis. Journal of Dermatological Science, Vol.2004,34:3～9
[12]Wu G, Osada M, Guo Z, et al. ANp63a up-regulates the Hsp70 gene in human cancer. Cancer Res,2005, Vol.65 (3):758～766
[13]Meera Patturajan, Shuji Nomoto, Matthias Sommer. ΔNp63 induces β-catenin nuclear accumulation and signaling. Cancer Cell, Vol.2002,1(4):369～379
[14]Hibi K, Trink B, Patturajan M, et al. AIS is an oncogene amplified in squamous cell carcinoma. Pmc Nail Acad Sci USA,2000, Vol.97(10):5462～5467
[15]Massion PP, Taflan PM, Jamshedur Rahman SM, et al. Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Research,2003, Vol.63: 7113～7121
[16]Redon R, Muller D, Aculee K, et al. A simple specific pattern of chromosomal aberrations at early stages of head and neck squamous cell carcinomas:PIK3CA but not p63 gene as a likely target of 3q26-qter gains. Cancer Res,2001, Vol.61:4122～4129
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[1]Schmal E H, Bamberger C. A novel protein wit h strong homology to the tumor suppressor p53. Oncogene,1997, Vol.15(11):1363～1367
[2]Yanggy A, Kaghad M, Wang Y, et al. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell, 1998, Vol.2 (3):305～316
[3]Marina Mangiulli, Alessio Valletti, Mariano Francesco Caratozzolo, et al. Identification and functional characterization of two new transcriptional variants of the human p63 gene. Nucleic Acids Research,2009, Vol.37(18):6092～6104
[4]Lu P, Barad M, Vize PD, et al. p63 expression in early ectoderm and neurectoderm. Mech, 2001, Vol.102(1-2):275～278.
[5]王帅,薛永来,冯喜增.p63基因的结构与功能生命科学.生命科学,2007,19(4)：446～450
[6]A. Yang, R. Schweitzer, D. Sun, et al, p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development, Nature,1999, Vol.398:714～718
[7]Mills A.A., Zheng B., Wang X.J., et al, p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature,1999, Vol.398:708～713
[8]Osada M,Kawahara C, et al. Cloning and funcitional analysis of human p51, which stiucturally and functionally resembles p53[J].Nat, Med,1998, Vol.4 (7):839～843.
[9]Weber A, Langhankil L, Schutz A, et al. Expression profiles of p53, p63, and p73 in benign salivary glan tumors. Virchows Arch,2002, Vol.441:428～436
[10]Yang AJ, Kaghad M, W ang Y, et al. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death inducing, and dominantnegative. Mol cell,1998, Vol. 2(3):305～316
[11]Maranke I, Kostera, Dennis R, et al. The role of p63 in development and differentiation of the epidermis. Journal of Dermatological Science, Vol.2004,34:3～9
[12]Wu G, Osada M, Guo Z, et al. ANp63a up-regulates the Hsp70 gene in human cancer. Cancer Res,2005, Vol.65 (3):758～766
[13]Meera Patturajan, Shuji Nomoto, Matthias Sommer. ΔNp63 induces β-catenin nuclear accumulation and signaling. Cancer Cell, Vol.2002,1(4):369～379
[14]Hibi K, Trink B, Patturajan M, et al. AIS is an oncogene amplified in squamous cell carcinoma. Pmc Nail Acad Sci USA,2000, Vol.97(10):5462～5467
[15]Massion PP, Taflan PM, Jamshedur Rahman SM, et al. Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Research,2003, Vol.63: 7113～7121
[16]Redon R, Muller D, Aculee K, et al. A simple specific pattern of chromosomal aberrations at early stages of head and neck squamous cell carcinomas:PIK3CA but not p63 gene as a likely target of 3q26-qter gains. Cancer Res,2001, Vol.61:4122～4129
[17]Richard Redon, Thomas Hussenet, Gaetan Bour, et al. Amplicon mapping and transcriptional analysis pinpoint cyclin L as a candidate oncogene in head and neck cancer. Cancer Res, 2002, Vol.62:6211～6217
[18]Guan XY, JST Sham, T Tang, et al. Isolation of a novel candidate oncogene within a frequently amplified region at 3q26 in ovarian cancer. Cancer Res,2001, Vol.61:3806～ 3809
[19]徐冬梅,唐良萏.P63基因与宫颈癌及癌前病变.中国实用妇科与产科杂志,2008,24(11)：864～866
[20]Regauer S, Reich O. CK17 and p16 expression patterns distinguish (atypical) immature squamous metaplasia from high-gradecervical intraepithelial neoplasia (CIN Ⅲ). Histopathology,2007, Vol.50 (5):629～635
[21]BJ Quade, A Yang, Y Wang, et al. Expression of the p53 Homologue p63 in Early Cervical Neoplasia. Gynecologic Oncology,2001, Vol.80(1):24～29
[22]贾英,吴瑾,唐良萏.宫颈癌前病变中ANP63与HPV16 E7表达的研究.重庆医科大学学报,2005,30(6)：846～848
[23]Lin Z, Nan Y, Zhang X, et al. Reverse transcription-polymerase chain reaction and western blotting analysis for detection of p63 isoforms in uterine cervical cancers. Int J Gynecol Cancer,2006, Vol.16 (4):1643～1647
[24]Drew PA, Hong B, Massoll NA, et al. Characterization of papillary squamotransitional cell carcinoma of the cervix. Low Genit Tract Dis,2005, Vol.9(3):149～150
[25]Cho NH, Kim YB, Park TK, et al. P63 and EGFR as prognostic predictors in stage ⅡB radiation-treated cervical squamous cell carcinoma. Gynecol Oncol,2005, Vol.98(2):335～ 336
[26]Lee JJ, Kim S, Yeom YI, et al. Enhanced specificity of the p53 family proteins-based adenoviral gene therapy in uterine cervical cancer cells with E2F1-responsive promoters. Cancer Biol Ther,2006, Vol.5 (11):1502～1510
[27]胡文芳,刘铭球,赵青.子宫内膜样腺癌组织中p53、p63和c-erb2的表达及其意义.癌症,2004,23(9)：1021～1025
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[29]Stefansson IM, Salvesen HB, Akslen LA. Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients. Int J Cancer, 2006, Vol.118(5):1227～1233
[30]Kaufmann O, Fietze E, M engs J, et al. Value of p63 and cytokerat in 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am J Clin Pathol,2001, Vol.116(6):823～830
[31]Wang Y, Kringen P, Kristensen GB, et al. Effect of the codon 72 polymorphism (c.215G> C, p.Arg72Pro) in combination with somatic sequence variants in the TP53 gene on survival in patients with advanced ovarian carcinoma. Hum Mutat,2004, Vol.24(1):21～34.
[32]Poli Neto OB, Candido Dos Reis FJ, Zambelli Ramalho LN, et al. p63 expression in epithelial ovarian tumors. International journal of gynecological cancer,2006, Vol.16(1): 152～155
[33]Higashikawa K, Yoneda S, Tobiume K, et al. Snail-induced down-regulation of DeltaNp63alpha acquires invasive phenotype of human squamous cell carcinoma. Cancer Res.2007, Vol.67(19):9207～9213
[34]Yanai H, Takahashi N, Omori M, et al. Immunohistochemistry of p63 in primary and secondary vulvar Paget's disease. Pathology International,2008, Vol.58(10):648～651
[35]Shih, Ie-Ming MD, Kurman, et al. p63 Expression Is Useful in the Distinction of Epithelioid Trophoblastic and Placental Site Trophoblastic Tumors by Profiling Trophoblastic Subpopulations. The American Journal of Surgical Pathology,2004 Vol.28(9):1177～1183
[36]Zhang HJ, Xue WC, Siu MK, et al. P63 Expression in Gestational Trophoblastic Disease: Correlation With Proliferation and Apoptotic Dynamics. Int J Gynecol Pathol,2009, Vol. 28(2):172～178
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