Kawasaki H, Altieri D C, Lu C D, Toyoda M, Tenjo T, Tanigawa N
Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Japan.
Cancer Res. 1998 Nov 15;58(22):5071-4.
Deregulated inhibition of apoptosis (programmed cell death) may facilitate the insurgence of neoplasia, but whether it also influences the outcome of common cancers has remained controversial. In this study, we investigated the expression of a novel inhibitor of apoptosis, survivin, in colorectal cancer and its relationship with tumor cell apoptosis and overall prognosis. By immunohistochemistry, survivin was expressed in 91 of 171 (53.2%) cases of colorectal carcinomas of histological stages 0 to IV. In contrast, normal colon epithelium did not express survivin. Although survivin expression did not correlate with p53 abnormalities (46.5% versus 58.0%; P = 0.18), survivin-positive cases were strongly associated with bcl-2 expression (72.5% versus 27.4%; P < 0.0001) and reduced apoptotic index (0.76% +/- 0.39% versus 1.17% +/- 0.62%; P < 0.0001). Expression of survivin alone in bcl-2-negative (discordant) cases also resulted in reduced apoptotic index (0.82% +/- 0.57% versus 1.16% +/- 0.66%; P = 0.0046). When analyzed for prognostic significance, patients with low apoptotic index (< 0.97%) had worse survival rates than the group with high apoptosis (P < 0.001), and a multivariate Cox proportional hazard model identified reduced apoptosis as an independent predictive factor for overall survival (P < 0.0001). These data demonstrate that apoptosis inhibition by survivin, alone or in cooperation with bcl-2, is an important predictive/prognostic parameter of poor outcome in colorectal carcinoma and identify survivin as a new diagnostic/therapeutic target in cancer.
凋亡（程序性细胞死亡）抑制失调可能会促进肿瘤形成，但它是否也会影响常见癌症的预后仍存在争议。在本研究中，我们调查了一种新型凋亡抑制剂生存素在结直肠癌中的表达及其与肿瘤细胞凋亡和总体预后的关系。通过免疫组织化学方法，在171例组织学分期为0至IV期的结直肠癌病例中，有91例（53.2%）表达了生存素。相比之下，正常结肠上皮不表达生存素。虽然生存素表达与p53异常无关（46.5%对58.0%；P = 0.18），但生存素阳性病例与bcl-2表达密切相关（72.5%对27.4%；P < 0.0001），且凋亡指数降低（0.76%±0.39%对1.17%±0.62%；P < 0.0001）。在bcl-2阴性（不一致）病例中单独表达生存素也会导致凋亡指数降低（0.82%±0.57%对1.16%±0.66%；P = 0.0046）。在分析预后意义时，凋亡指数低（< 0.97%）的患者生存率低于高凋亡组（P < 0.001），多变量Cox比例风险模型确定凋亡减少是总体生存的独立预测因素（P < 0.0001）。这些数据表明，生存素单独或与bcl-2协同抑制凋亡是结直肠癌预后不良的重要预测/预后参数，并确定生存素为癌症新的诊断/治疗靶点。
