Immunohistochemical expression of molecular markers in an avian model:: A potential model for preclinical evaluation of agents for ovarian cancer chemoprevention
Immunohistochemical expression of molecular markers in an avian model:: A potential model for preclinical evaluation of agents for ovarian cancer chemoprevention
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DOI：
10.1006/gyno.2001.6191
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发表时间：
2001-06-01
影响因子：
4.7
通讯作者：
Grizzle, WE
中科院分区：
文献类型：
--
作者：
Rodríguez-Burford, C;Barnes, MN;Grizzle, WE
目标。评价潜在的卵巢癌化学预防化合物面临的一个重要障碍是缺乏自发的卵巢癌发生的动物模型。一种潜在的腺癌模型已在蛋鸡中被描述。这项研究的目的是评估在这一潜在的上皮性癌模型中用于化学预防研究的可用抗体的免疫组织化学表达。根据IUACUC的指导方针，200只2岁的母鸡在奥本大学被宰杀。在这些母鸡中，有8只被认为患有卵巢癌和腹水。将8只母鸡的肿瘤固定在中性缓冲福尔马林中，制成石蜡切片。苏木精-伊红染色证实腺癌的组织学存在。用CA125、CEA、细胞角蛋白、EGFR、erbB-2、Ki-67、Lewis Y、p27、增殖细胞核抗原、标记72、转化生长因子-α、MUC-1、MUC-2等抗体进行免疫组织化学检测。经病理学家的显微镜检查，8个标本被记录为腺癌。在人类卵巢癌中经常表达的几种抗原抗体在产蛋母鸡中发生交叉反应。其中，细胞角蛋白AE1/AE3、PAN细胞角蛋白、EGFR、Lewis Y、CEA、Tag 72和erbB-2对鸡癌进行了染色。EGFR和p185(erbB-2)广泛表达，细胞角蛋白AE1/AE3、PAN细胞角蛋白、Lewis Y、CEA和Tag 72局部阳性。上述抗体可作为化学预防试验的替代终点，并对鸡癌进行染色，包括增殖细胞核抗原、p27和转化生长因子-α抗体，而不具有交叉反应的抗体包括CA125、Ki-67、MUC 1和MUC 2。这项初步研究中提出的数据支持了研究化学预防药物的自发性腺癌禽类模型的潜在用途。更重要的是，化学预防方案对相关抗原表达的影响可以使用在该模型中具有交叉反应的可用抗体来确定。因此，由交叉反应抗体识别的替代终点生物标记物表型表达的变化有助于人类卵巢癌化学预防试验的发展。(C)2001年学术出版社。
Objective. A significant obstacle confronting the evaluation of potential chemopreventive compounds in ovarian carcinoma is the absence of an animal model of spontaneous ovarian carcinogenesis. A potential model of adenocarcinoma has been described in the laying hen (Gallus domesticus). The purpose of this study was to evaluate the immunohistochemical expression of available antibodies that have been utilized in chemoprevention studies in this potential model of epithelial carcinoma.Methods. Two hundred 2-year-old hens were sacrificed at Auburn University in accordance with IUACUC guidelines. Of these hens, 8 animals were thought grossly to have ovarian carcinoma and ascites. The tumors from these 8 hens were fixed in neutral-buffered formalin and processed to paraffin blocks. Hematoxylin and eosin stains were used to document the histologic presence of adenocarcinoma. Immunohistochemical evaluation for expression of antigen was performed using the following antibodies: CA125, CEA, cytokeratin, EGFR, erbB-2, Ki-67, Lewis Y, p27, PCNA, Tag 72, TGF-alpha, Muc 1, and Muc 2.Results. Upon microscopic examination by a pathologist eight specimens were documented as adenocarcinomas. Several antibodies to antigens that are frequently expressed in human ovarian cancer were cross-reactive in the laying hen. Of these, cytokeratin AE1/AE3, pan cytokeratin, EGFR, Lewis Y, CEA, Tag 72, and erbB-2 stained the chicken carcinomas. EGFR and p185(erbB-2) stained diffusely, and cytokeratin AE1/AE3, pan cytokeratin, Lewis Y, CEA, and Tag 72 were focally positive in the tumor. The aforementioned antibodies which have been useful as surrogate endpoints in chemoprevention trials and which also stained the chicken carcinomas included PCNA, p27, and TGF-alpha Antibodies that were not cross-reactive include CA 125, Ki-67, Muc 1, and Muc 2.Conclusion. The data presented in this pilot study support the potential utility of an avian model of spontaneously arising adenocarcinoma in which to study chemopreventive agents. More importantly, the influence of chemoprevention protocols on the expression of relevant antigens can be determined using available antibodies that are cross-reactive in this model. Thus, changes in the phenotypic expression of surrogate endpoint biomarkers as identified by cross-reactive antibodies can aid in the development of chemoprevention trials for human ovarian cancer. (C) 2001 Academic Press.