FUNCTIONAL ANALYSIS OF P73 GENE AND P51/P63 GENE IN HUMAN MAMMARY TISSUE AND MAMMARY CARCINOMA

为了避免p73表达细胞的污染，本研究采用免疫组化方法研究了p73在乳腺癌中的表达。本研究的目的是评估p73蛋白作为乳腺癌高级别恶性潜能的参数的有用性。设计：我们通过标准技术开发了抗p73多克隆抗体。用谷胱甘肽S-转移酶（GST）-p73（从TQWKRCPNH到YEPPQVGTEF的氨基酸）免疫家兔以产生抗p73抗体。从75例乳腺癌患者的乳房切除术中获取浸润性乳腺癌和非肿瘤性乳腺组织标本。结果：20例乳腺癌组织中p73蛋白阳性表达率为20%（p73（+）），而75例肌上皮组织中p73蛋白阳性表达率为100%（P < 0.05）。p73（+）组的细胞凋亡指数（AI）（中位数，范围）（2.01，1.14-6.56%）显著高于p73（-）组（0.48，0.06-4.90%）（p < 0.05）。p73（+）组的核分裂指数（MI）（中等范围）（2.00，1.08-3.42%）显著高于p73（-）组（0.37，0.01-2.41%）（p < 0.05）。本组4例远处转移瘤均显示高MI（>1%）和P73（-）。22例（29.3%）p53过表达（p53（+））。P73（+）/p53（+）的AI（中位数，范围）（2.17%（0.1-3.41%））显著高于P73（-）/p53（+）的AI（1.12%，0.25-2.40%）（p<0.05）。P73蛋白在肌上皮中表达. P73蛋白在高MI乳腺癌中的表达可能在乳腺癌的诱导分化中起作用. p73蛋白表达缺失可能与晚期胃癌的发生和转移有关. P73蛋白甚至在p53过度表达的情况下也可能起作用。

In the present study, expression of p73 in mammary carcinoma was studied immunohistochemically to avoid the contamination of the cells expressing p73. The aim of this study is to evaluate usefulness of p73 protein as a parameter of high-grade malignant potential in mammary carcinoma.Design : We developed anti-p73 polyclonal antibody by standard techniques. Rabbit was immunized with glutattjione S-transferase (GST) -p73 (ammo acids from TQWKRCPNH to YEPPQVGTEF) for the production of anti-p73 antibody. Tissue specimens of invasive mammary carcinomas and nonneoplastic mammary tissue were Obtained from 75 patients with mammary carcinoma undergoing mastectomies. Immunohistochemical expression of p53 (DO-7, PharMingen International), the apoptotic index (AI) and the mitotic index (MI) were also examined.Results : Immunohistochemical expression of p73 was evident in 20 mammary carcinomas (20%, p73 (+)), while myoepithelium showed immunohistochemical expression of p73protein in all 75cases (100%). The apoptotic index (AI) (medium, range) of p73 (+) cases (2.01, 1.14-6.56%) was significantly higher than those of 73 (-) cases (0.48, 0.06-4.90%)(p < 0.05). The mitotic index (MI) (medium, range) of p73 (+) cases (2.00, 1.08-3.42%) was significantly higher than those of p73 (-) cases (0.37, 0.01-2.41%)(p < 0.05). All 4 cases with distant metastases in this series showed high MI (>1%) and P73 (-). 22 cases (29.3%) showed overexpression of p53 (p53 (+)). The AI (median, range) of P73(+)/p53 (+)(2.17% (0.1-3.41%)) was interestingly higher than P73(-)/p53 (+) (1.12%, 0.25-2.40%) (p<0.05).Conclusion : Results of the present study.suggest : 1. P73 protein expressed in myoepithelium.2. P73 protein expressed in mammary carcinoma showing high MI may play a role in the induction of apoptosis.3. The loss of p73 expression may be associated with advanced carcinogenesis and metastatic potential.4. P73 protein may functions even in cases showing p53 overexpression.