al-Sheneber I F, Shibata H R, Sampalis J, Jothy S
Department of Surgery, Royal Victoria Hospital, Montreal, Quebec, Canada.
Cancer. 1993 Mar 15;71(6):1954-9. doi: 10.1002/1097-0142(19930315)71:6<1954::aid-cncr2820710605>3.0.co;2-#.
Recognition of a biologic marker in colorectal cancer tissue that correlates with recurrence and poor survival would offer a rationale for planning aggressive adjuvant therapy. This study assessed the prognostic significance of proliferation activity in cancer cells and nonneoplastic epithelial cells in patients with colorectal cancer, using proliferating cell nuclear antigen (PCNA) immunohistochemical analysis.
A mouse monoclonal antibody that reacted with PCNA was used to measure proliferation indexes in neoplastic and nonneoplastic colonic tissues of two sex-matched and age-matched groups of 40 patients with different clinical outcomes. In one group of 20 patients, there was no evidence of recurrence or residual disease after a median follow-up of 5.3 years. In the other group, all 20 patients had died within 3.6 years of recurrent disease.
The proliferation indexes in both cancer cells and epithelial cells of adjacent nonneoplastic crypts were elevated significantly in those who died compared with survivors; this finding was independent of other variables. There was evidence of an upward shift in the proliferation compartment of the normal crypt that occurred to the same extent in both patient groups. No correlation between Dukes stage and any of the proliferation indexes was observed.
Proliferation indexes in neoplastic and adjacent normal mucosa, as defined by PCNA immunohistochemical analysis, are independent predictors of recurrence and poor survival in patients with colorectal cancer, indicating that they may be helpful as predictors of long-term survival and in planning prophylactic adjuvant therapy.
识别与结直肠癌复发及生存不良相关的生物学标志物可为制定积极的辅助治疗方案提供依据。本研究采用增殖细胞核抗原（PCNA）免疫组化分析，评估结直肠癌患者癌细胞和非肿瘤性上皮细胞增殖活性的预后意义。
使用一种与PCNA反应的小鼠单克隆抗体，测量两组40例临床结局不同的性别和年龄匹配患者的肿瘤性和非肿瘤性结肠组织中的增殖指数。在一组20例患者中，中位随访5.3年后无复发或残留疾病证据。在另一组中，所有20例患者均在复发性疾病3.6年内死亡。
与存活者相比，死亡患者的癌细胞和相邻非肿瘤性隐窝上皮细胞的增殖指数均显著升高；这一发现与其他变量无关。有证据表明正常隐窝增殖区出现上移，在两组患者中程度相同。未观察到Dukes分期与任何增殖指数之间的相关性。
PCNA免疫组化分析所定义的肿瘤性及相邻正常黏膜的增殖指数是结直肠癌患者复发和生存不良的独立预测指标，表明它们可能有助于预测长期生存及制定预防性辅助治疗方案。
