Hershey A E, Dubielzig R R, Padilla M L, Helfand S C
Department of Medical Sciences, Oregon Cancer Center for Animals, College of Veterinary Medicine, Oregon State University, Magruder Hall, Corvallis, OR 97331, USA.
Vet Pathol. 2005 Nov;42(6):805-11. doi: 10.1354/vp.42-6-805.
Eighty spontaneously occurring feline vaccine-associated sarcomas (VAS) were evaluated to determine the immunohistochemical expression of the tumor suppressor gene p53. Sixty-five of 80 VAS (81%) exhibited positive immunoreactivity with Mab240, a murine monoclonal antibody that specifically recognizes mutated p53. Only 44 of 81 tumors (55%) were positive with rabbit polyclonal antibody CM-1. CM-1 often yielded nonspecific staining of nonneoplastic tissues. Nonspecific staining was greatly reduced or absent with Mab240. Cytoplasmic staining for p53 was a consistent pattern of VAS, occurring in 44% of tumors evaluated. Cats with tumors that exhibited cytoplasmic p53 had significantly shorter time to tumor recurrence compared to those cats with tumors that exhibited nuclear p53 staining (P = 0.0284), but no significant difference in survival outcome was observed. Immunohistochemical detection of p53 offers a prognostic tool for VAS, and, because abnormal p53 expression appears to be a common feature of feline VAS, molecular targeting of mutant p53, may offer a promising new therapeutic opportunity for this cancer.
对80例自发产生的猫疫苗相关肉瘤(VAS)进行评估,以确定肿瘤抑制基因p53的免疫组化表达。80例VAS中有65例(81%)与Mab240呈阳性免疫反应,Mab240是一种特异性识别突变型p53的鼠单克隆抗体。81个肿瘤中只有44例(55%)对兔多克隆抗体CM-1呈阳性。CM-1常导致非肿瘤组织的非特异性染色。Mab240可大大减少或消除非特异性染色。p53的细胞质染色是VAS的一种一致模式,在所评估的肿瘤中有44%出现这种情况。与肿瘤表现为核p53染色的猫相比,肿瘤表现为细胞质p53的猫肿瘤复发时间显著缩短(P = 0.0284),但在生存结果方面未观察到显著差异。p53的免疫组化检测为VAS提供了一种预后工具,而且由于p53异常表达似乎是猫VAS的一个共同特征,对突变型p53进行分子靶向治疗可能为这种癌症提供一个有前景的新治疗机会。