Proliferative activity and malignancy in human gastric cancers. Significance of the proliferation rate and its clinical application.

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.