Tumor proliferation and apoptosis in human uterine cervix carcinoma I: Correlations between variables

Purpose: Parameters for tumor proliferation and apoptosis were studied pros pectively in 84 previously untreated patients with a diagnosis of carcinoma of the uterine cervix. Materials and methods: Tumor proliferation was assessed by in vivo labeling with bromodeoxyuridine (BrdU), followed by a biopsy of the tumor 4-10 h th ereafter during an examination under anesthesia. The potential doubling tim e (T-pot) was obtained by deriving the BrdU labeling index (LI) and S-phase duration (T-s) using Row cytometry. The LI for BrdU and its staining patte rn were also determined immunohistochemically. Apoptosis was assessed histo logically using morphological criteria. Results: Seven patients were excluded and the FIGO stages of the remaining 77 patients were as follows: IB and IIA, 20 patients; IIB, 29 patients; III B and IV, 28 patients. The median tumor diameter was 6 cm. There were 61 sq uamous cell, 11 adeno- and five adenosquamous carcinomas. Of the 63 patient s in whom the tumor grade could be determined, 37 were well or moderately w ell differentiated and the remaining 26 were poorly differentiated. The med ian mitotic index (MI) was 0.7%. There were 43 diploid and 34 aneuploid tum ors. Median values for T-s and S-phase fraction (SPF) were 9.9 h and 16%, r espectively. The median BrdU LI by Row cytometry (LI-fc) was 6.7%. There wa s a significant correlation between LI-fc and LI by histology, although val ues for the latter(median 11.1%) were consistently higher than those determ ined by flow cytometry by a factor of 1.5. The median T-pot value was 5.0 d ays. The median apoptotic index (AI) was 1.0% and AI correlated positively with LI-fc. Median values for LI-fe increased with increasing tumor size an d were 5.1%, 6.4%, 7.5% and 11.0% for tumors measuring less than or equal t o 4.cm, 4-6 cm, 6-8 cm and > 8 cm, respectively. The remaining proliferatio n parameters, however, showed no correlation with tumor size, stage, grade or histologic type. Conclusions: In carcinomas of the cervix, tumor proliferation is positively associated with apoptosis and tumor size. These findings suggest that para meters for tumor proliferation and apoptosis are associated with tumor prog ression and may thus be predictive of clinical outcome. (C) 1999 Elsevier S cience Ireland Ltd. All rights reserved.