Zuccari Debora A P C, Santana Aureo E, Cury Patrícia M, Cordeiro José Antônio
Clinics and Surgery Department, FCAV, UNESP, Jaboticabal (SP), Brazil.
Vet Clin Pathol. 2004;33(1):23-8. doi: 10.1111/j.1939-165x.2004.tb00345.x.
Canine mammary tumors are challenging for clinicians and pathologists because of complex histologic classification, low specificity of cytologic diagnosis, and unpredictable biological behavior. In histologic specimens, expression of tumor proliferation marker Ki-67, a nuclear nonhistone protein, has been shown to have prognostic value for canine mammary tumors and to correlate with malignancy and low survival rates.
The objective of this study was to measure the proliferation index of canine mammary tumors by immunochemical detection of Ki-67 in cytologic specimens and to determine its relationship to clinical and pathologic variables and patient outcome.
Spontaneous mammary tumors from 31 female dogs were surgically excised. Imprint specimens for cytologic evaluation were wet-fixed in ethanol; histologic specimens were prepared routinely. Immunostaining was performed with the PH 177 monoclonal antibody against Ki-67; proliferation index was graded from negative to +++. Dogs were followed for 18 months. Multivariate logistic regression analysis was used to determine correlations between immunocytochemical results, tumor and clinical variables, and patient outcome.
Ki-67 proliferation indices in cytologic specimens were significantly lower for nonmalignant tumors than for malignant tumors. High index values of Ki-67 were positively correlated with metastasis, death from neoplasia, low disease-free survival rates, and low overall survival rate. With the exception of 4 specimens for which cellularity was insufficient, positive expression of Ki-67 in cytologic specimens correlated with that of histologic specimens.
The prognostic value of the Ki-67 index in canine mammary tumors by using wet-fixed cytology imprint specimens was similar to that observed previously for histologic specimens. Immunocytochemical detection of Ki-67 could improve the accuracy and value of cytology by providing safe and rapid information about malignancy and patient outcome.
犬乳腺肿瘤对临床医生和病理学家来说颇具挑战，因为其组织学分类复杂、细胞学诊断特异性低且生物学行为不可预测。在组织学标本中，肿瘤增殖标志物Ki-67（一种核非组蛋白）的表达已被证明对犬乳腺肿瘤具有预后价值，且与恶性程度及低生存率相关。
本研究的目的是通过免疫化学检测细胞学标本中的Ki-67来测量犬乳腺肿瘤的增殖指数，并确定其与临床和病理变量及患者预后的关系。
对31只雌性犬的自发性乳腺肿瘤进行手术切除。用于细胞学评估的印片标本用乙醇湿固定；组织学标本常规制备。用抗Ki-67的PH 177单克隆抗体进行免疫染色；增殖指数从阴性到+++分级。对犬进行18个月的随访。采用多变量逻辑回归分析来确定免疫细胞化学结果、肿瘤和临床变量与患者预后之间的相关性。
非恶性肿瘤细胞学标本中的Ki-67增殖指数显著低于恶性肿瘤。Ki-67的高指数值与转移、肿瘤死亡、低无病生存率和低总生存率呈正相关。除4份细胞数量不足的标本外，细胞学标本中Ki-67的阳性表达与组织学标本的阳性表达相关。
使用湿固定细胞学印片标本检测犬乳腺肿瘤中Ki-67指数的预后价值与先前在组织学标本中观察到的相似。通过提供有关恶性程度和患者预后的安全快速信息，Ki-67的免疫细胞化学检测可提高细胞学的准确性和价值。
