Immunohistochemical analysis of MIB-1 proliferative activity in human endometrial cancer. Correlation with clinicopathological parameters, patient outcome, retinoblastoma immunoreactivity and K-ras codon 12 point mutations

To test the prognostic utility of MIB-1 in human endometrial neoplasias, th e proliferative activities of fifty-two endometrial carcinomas obtained fro m Polish women were assessed. We also investigated the relationship between the MIB-1 Proliferative Index and the well-known clinicopathological featu res of cancer (clinical stage, histological type, histological grade, depth of myometrial invasion), patient's age, overall survival, retinoblastoma i mmunostaining and K-ras codon 12 point mutations. The mean MIB-1 Proliferat ion Index was 43.8%, with a median of 36.0%. Due to the great intratumour h eterogeneity of the immunoreaction, the Index ranged from 0% to 98%. A sign ificant relationship was noted between MIB-1 expression and histological gr ading (p=0.0004) and myometrial invasion of cancer (p=0.01). Multivariate C ox regression demonstrated that the clinical stage was the only independent prognostic factor during follow-up (p=0.025). There was a tendency towards a poorer outcome for women with a Proliferative Index of > 31% than for pa tients whose Index was less than or equal to 31%; the difference, however, did not reach significance (p=0.25; log-rank test). Interestingly, uterine cancers lacking retinoblastoma protein expression had a mean MIB-1 Prolifer ation Index that was nearly twice as high as in those neoplasias that stain ed positively for retinoblastoma (70.33% and 42.14%, respectively; p=0.09; Mann-Whitney-U test). There were no significant differences between K-ras c odon 12 point mutation-positive and -negative endometrial carcinomas regard ing the proliferative activity of the cancer (mean Indexes 47.6% and 43.8%, respectively; p=0.66, Mann-Whitney-U test). Our data support the view that MIB-1 proliferative activity was significantly increased with a decrease o f the histological grading and with the myometrial invasion of human endome trial cancer.