Proliferation to apoptosis ratio as a prognostic marker in adenocarcinoma of uterine cervix

Abstract

Objectives. To determine the Mitotic Index (MI), Apoptotic Index (AI), the ratio of the two indices (MI/AI) in normal endocervical glands, adenocarcinoma in situ (AIS) and invasive adenocarcinoma of cervix, and to evaluate the relationship among these indices with various clinicopathological features. Methods. The MI, AI and MI/AI ratio in cervical adenocarcinoma were evaluated based on: (1) cell morphology in hematoxylin and eosin-stained sections; (2) immunohistochemical study for Ki67 antigen and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). Eighty cases of invasive adenocarcinoma and eighteen cases of adenocarcinoma in situ (AIS) adjacent to invasive adenocarcinoma were included. Adjacent normal endocervical epithelium in 26 cases of adenocarcinoma was included as control. Results. The MI, AI and MI/AI in normal endocervical glands, AIS and invasive carcinomas showed statistically significant differences (P < 0.001). A significant positive correlation was found between AI and MI, as assessed by morphological features (P < 0.001) and immunohistochemistry (P = 0.006). The MI/AI ratio, determined by morphology, significantly correlated with staging (P = 0.023) and survival (P = 0.0045). Multivariate survival analysis showed that both MI/AI ratio determined by morphology (P < 0.001) and stage of tumor (P = 0.03) had independent prognostic value in invasive adenocarcinoma. Conclusions. Tumor proliferation significantly correlated with apoptotic activity in cervical adenocarcinoma. The MI/AI ratio was an independent prognostic factor associated with patient survival. Histological determination of MI/AI ratio proved to be an economical and potentially useful adjunct in predicting clinical outcome of patients with cervical adenocarcinoma. © 2004 Elsevier Inc. All rights reserved.