DNA content, proliferation markers and histopathology as prognostic factors in Astrocytic tumours

University dissertation from Linköping : Linköpings universitet

Abstract: The DNA index and S-phase fractions obtained from freshly frozen and paraffin-embedded specimens of 49 primary intracranial tumors showed significant correlation. Very similar results were obtained when a subgroup of astrocytomas was analyzed. Thus, the feasibility of DNA-flow cytometry for retrospective studies of archival tumor specimens was confirmed.In a study of 134 astrocytomas a strong correlation between grade of malignancy, S-phase fraction and DNA ploidy type was seen. In multivariate Cox regression analysis of 60 cases with grade II or Ill astrocytomas, age, grade of malignancy, DNA ploidy and S-phase were independent prognostic factors. An age of under 50, grade II, low S-phase and tetraploid DNA pattern correlated with long survival.Twenty-two recurrent astrocytomas were investigated after primary and repeated surgery. The grade of malignancy had significantly increased at the time of re-operation. The S-phase also tended to increase while the DNA-index was essentially unchanged. In recurrent astrocytomas the original_grade of malignancy was the most important prognostic parameter, which significantly correlated with time to recurrence and with survival after reoperation. The recurrence-free interval was significantly shorter in patients over 50 years of age and patients with an aneuploid DNA pattern at the time of the first surgery. However, when DNA ploidy, histopathological grade and age were evaluated simultaneously in a multivariale analysis, DNA ploidy was not an independent prognostic indicator.A strong correlation was found between the cell replication measured as Ki-67 labeling index and grades of malignancy at primary and repealed surgery. When less than 10 percent of cells were stained by Ki-67 after primary surgery, patient survival was prolonged approximately three times compared to survival of patients with a high Ki-67 labeling index.

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