Nuclear morphometry and DNA flow cytometry as prognostic methods for endometrial carcinoma

In a series of 227 women with endometrial carcinoma stages I-IV the prognostic value of nuclear morphometry and DNA analysis was evaluated prospectively. The tumors were also classified according to histologic subtype, degree of differentiation (FIGO), and nuclear grade. The DNA analysis (ploidy and S-phase fraction) was made using flow cytometry on fresh-frozen tissue. The morphometric measurements and the grading of the tumors were done on both fresh-frozen tissue and on formalin-fixed and paraffin-embedded tissue. The rate of recurrence for the complete series was 14% with 2.2% vaginal metastases. The overall 5-year survival rate was 68% and the corrected survival rate 76%. The minimum nuclear diameter and the standard deviation (SD) of the maximum nuclear diameter were significant and independent prognostic variables in a Cox multivariate analysis when analyzed on paraffin-embedded tissue. The nuclear grade was the single most prognostically informative variable. A corresponding analysis on fresh-frozen tissue showed that the S-phase fraction and the FIGO grading of the tumor were significant variables. The morphometric variables and the nuclear grading were non-significant prognostic variables. Morphologic changes in tumor cell nuclei during the freezing and thawing procedures may explain the loss of prognostic information. A combination of DNA index (fresh-frozen tissue) and the mean values of the shortest nuclear diameter and the SD of the longest diameter (paraffin-embedded tissue) gave the best prognostic information vis-a-vis cancer-related death in an all-possible-subsets regression analysis.