Ohyama S, Yonemura Y, Miyazaki I
Department of Surgery II, School of Medicine, Kanazawa University, Japan.
Cancer. 1992 Jan 15;69(2):314-21. doi: 10.1002/1097-0142(19920115)69:2<314::aid-cncr2820690207>3.0.co;2-9.
The authors sought useful indicators for predicting the proliferative activity of human gastric cancer and attempted to evaluate its clinical significance. One hundred seventy-two patients with gastric cancer were entered in this study. All patients received bromodeoxyuridine at 200 to 1000 mg/body before laparotomy. Cell kinetics studies using the migration chase method were done for 56 patients, and the DNA synthesis time (Ts) was found to be prolonged in tumors, especially in aneuploid tumors, compared with normal mucosae. Ts correlated with bromodeoxyuridine (BrdUrd) labeling indices (LI) (r = 0.453, P less than 0.0005) and DNA indices (DI) (r = 0.534, P less than 0.0005). Thus, the DNA synthesis time was significantly prolonged in the tumors having a high S-phase fraction or DNA aneuploidy. The result of multivariate analysis indicated that LI/DI was the most potent indicator for predicting the proliferation rate (PR), which was calculated by the formula LI/Ts, and correlated significantly with PR (r = 0.863, P less than 0.0001). As was clear from the result of Cox's proportional hazard model, the predicted proliferation rate (pPR) was the most notable factor for the prognosis because pPR correlated clinically with metastasis, such as that to liver and lymph nodes. The patients with a high pPR (greater than 10%) had a worse prognosis (4-year survival rate: 16.3%) than did those with a low value (less than 10%) (4-year survival rate: 85.1%). In vitro pPR obtained by in vitro BrdUrd labeling of the specimens obtained at biopsy correlated significantly with the in vivo pPR (r = 0.960, P less than 0.0001). The authors concluded that the proliferation rate was the most important factor in judging the malignancy of human gastric cancers and that this rate should be most helpful in determining the treatment and evaluating the prognosis of individual patients.
作者们寻找预测人类胃癌增殖活性的有用指标，并试图评估其临床意义。172例胃癌患者纳入本研究。所有患者在剖腹手术前接受200至1000mg/体的溴脱氧尿苷。对56例患者采用迁移追踪法进行细胞动力学研究，发现与正常黏膜相比，肿瘤尤其是非整倍体肿瘤的DNA合成时间（Ts）延长。Ts与溴脱氧尿苷（BrdUrd）标记指数（LI）相关（r = 0.453，P＜0.0005），与DNA指数（DI）相关（r = 0.534，P＜0.0005）。因此，在具有高S期分数或DNA非整倍体的肿瘤中，DNA合成时间显著延长。多因素分析结果表明，LI/DI是预测增殖率（PR）的最有效指标，PR通过公式LI/Ts计算得出，且与PR显著相关（r = 0.863，P＜0.0001）。从Cox比例风险模型的结果可以看出，预测增殖率（ pPR）是预后的最显著因素，因为pPR在临床上与转移相关，如肝转移和淋巴结转移。pPR高（＞10%）的患者预后比pPR低（＜10%）的患者差（4年生存率：16.3%比85.1%）。活检标本体外BrdUrd标记获得的体外pPR与体内pPR显著相关（r = 0.960，P＜0.0001）。作者得出结论，增殖率是判断人类胃癌恶性程度的最重要因素，该比率对确定个体患者的治疗和评估预后最有帮助。
