Vail D M, Kisseberth W C, Obradovich J E, Moore F M, London C A, MacEwen E G, Ritter M A
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA.
Exp Hematol. 1996 Jun;24(7):807-15.
The predictive potential of several proliferation indices for therapeutic outcome was investigated in 55 dogs with spontaneously occurring non-Hodgkin's lymphoma (NHL). Indices included potential doubling time (Tpot), argyrophilic nucleolar organizer region (AgNOR) frequency, and proliferating cell nuclear antigen labeling index (PCNA-LI). All tumors were of intermediate- or high-grade histology as assessed by the Working Formulation, and all dogs presented with disease of advanced clinical stage. All tumors were treated with an identical chemotherapeutic protocol. Tpot determination by a bromodeoxyuridine (BrdU) delayed-biopsy technique was readily applied in the dog. AgNOR frequency and PCNA-LI were easily obtained from archival, formalin-fixed, paraffin-embedded canine tissues. When accounting for all other prognostic variables by employing multivariate analysis, Tpot (p=0.017), and AgNOR frequency (p=0.021), but not PCNA-LI, were predictive of first remission duration. AgNOR frequency (p=0.033) was also predictive of survival time, and the predictive potential of Tpot approached significance (p=0.076). We conclude that Tpot and AgNOR frequency can be used as predictors of outcome in dogs with NHL, and spontaneous NHL in the dog may have significant potential as a model for further characterization of the association between tumor cell kinetics and chemoresponsiveness.
在55只患有自发性非霍奇金淋巴瘤（NHL）的犬中，研究了几种增殖指数对治疗结果的预测潜力。这些指数包括潜在倍增时间（Tpot）、嗜银核仁组织区（AgNOR）频率和增殖细胞核抗原标记指数（PCNA-LI）。根据工作分类法评估，所有肿瘤均为中级别或高级别组织学类型，并且所有犬均呈现临床晚期疾病。所有肿瘤均采用相同的化疗方案进行治疗。通过溴脱氧尿苷（BrdU）延迟活检技术测定Tpot在犬中很容易应用。AgNOR频率和PCNA-LI很容易从存档的、福尔马林固定、石蜡包埋的犬组织中获得。当通过多变量分析考虑所有其他预后变量时，Tpot（p = 0.017）和AgNOR频率（p = 0.021），而非PCNA-LI，可预测首次缓解持续时间。AgNOR频率（p = 0.033）也可预测生存时间，并且Tpot的预测潜力接近显著水平（p = 0.076）。我们得出结论，Tpot和AgNOR频率可作为犬NHL预后的预测指标，并且犬自发性NHL可能具有作为进一步表征肿瘤细胞动力学与化疗反应性之间关联模型的显著潜力。
