Sarli Giuseppe, Preziosi Rosario, Benazzi Cinzia, Castellani Gastone, Marcato Paolo Stefano
Department of Veterinary Public Health and Animal Pathology, Division of Veterinary Pathology, via Tolara di Sopra 50-40064 Ozzano Emilia, Bologna, Italy.
J Vet Diagn Invest. 2002 Jan;14(1):25-34. doi: 10.1177/104063870201400106.
The aim of this study was to investigate the correlation between the histologic invasiveness (histologic stage) and various cell proliferation activity assays (quantity of argyrophil proteins associated with nucleolar organizer regions [AgNORs], mitotic activity, MIB1 [Ki67] immunohistochemical detection) for predicting the biologic behavior of malignant canine mammary tumors. Sixty specimens from malignant canine mammary tumors with no distant metastases (M0) at surgery were selected, and follow-up data were collected over a 2-year period. The histologic invasiveness was graded by histologic stage (stage 0 = tumors without stromal invasion; stage I = tumors with stromal invasion; stage II = tumors with neoplastic emboli in vessels), and the proliferative indices were expressed as MIB1 index (the percentage of nuclear area immunohistochemically stained by MIB1 antibody), mitotic index (the number of mitoses per 1,000 neoplastic cells), and AgNOR index (the ratio between mean AgNOR area of tumor cells and the mean AgNOR area of fibroblasts/lymphocytes). The measures of proliferative activity were compared among groups with different histologic stages, and the influence of different prognostic variables (histologic stage, AgNOR index, mitotic index, MIB1 index) on survival time was evaluated. A significant difference in the proliferation patterns was recorded between the different histologic stages for the mitotic index (P = 0.0006) and MIB1 index (0.0013). Among the different parameters considered, histologic stage (P < 0.05), AgNOR index (P = 0.0291), and MIB1 index (P = 0.014) revealed a significant association with prognosis in univariate analysis. AgNOR index for 1-year survival and histologic stage for 2-year survival were the most significant parameters influencing survival, as determined by multiple nonlinear logistic regression.
本研究的目的是调查组织学侵袭性（组织学分期）与各种细胞增殖活性检测方法（与核仁组成区相关的嗜银蛋白[AgNORs]数量、有丝分裂活性、MIB1[Ki67]免疫组织化学检测）之间的相关性，以预测犬恶性乳腺肿瘤的生物学行为。选取了60例手术时无远处转移（M0）的犬恶性乳腺肿瘤标本，并在2年期间收集随访数据。组织学侵袭性根据组织学分期分级（0期 = 无基质浸润的肿瘤；I期 = 有基质浸润的肿瘤；II期 = 血管中有肿瘤栓子的肿瘤），增殖指数表示为MIB1指数（MIB1抗体免疫组织化学染色的核面积百分比）、有丝分裂指数（每1000个肿瘤细胞中的有丝分裂数）和AgNOR指数（肿瘤细胞平均AgNOR面积与成纤维细胞/淋巴细胞平均AgNOR面积之比）。比较不同组织学分期组之间的增殖活性指标，并评估不同预后变量（组织学分期、AgNOR指数、有丝分裂指数、MIB1指数）对生存时间的影响。不同组织学分期之间，有丝分裂指数（P = 0.0006）和MIB1指数（0.0013）的增殖模式存在显著差异。在考虑的不同参数中，组织学分期（P < 0.05）、AgNOR指数（P = 0.0291）和MIB1指数（P = 0.014）在单因素分析中显示与预后有显著关联。通过多元非线性逻辑回归确定，1年生存率的AgNOR指数和2年生存率的组织学分期是影响生存的最显著参数。
