DNA ploidy status, S-phase fraction, and p53 are not independent prognostic factors for survival in endometrioid endometrial carcinoma FIGO stage I–III

Abstract

ObjectivesTo assess the effects on relative survival of established and new prognostic factors in stage I–III grade 1–3 endometrioid endometrial carcinoma and in the subgroup of stage I grade 1–2.MethodsThis was a population-based, retrospective study including all women (n=1113) in the western Swedish healthcare region diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I–III grade 1–3 endometrioid endometrial carcinoma in 2006–2011. Histology, grade, stage, and age were prospectively reported to the regional clinical and national cancer registers. DNA ploidy and S-phase fraction were analyzed by flow cytometer. S-phase fraction cut-off was set at ≥8%. Tumor biopsies were classified as diploid if there was one G0/G1 peak or the DNA index was 1.0±0.04. Overexpression of p53 as determined by immunohistochemistry was positive if strong nuclear staining was found in >30% of the neoplastic cells.ResultsBased on univariable statistical analyses we found that 5-year relative survival was significantly associated with S-phase fraction, DNA ploidy, p53, stage, grade, and age. Excess mortality for S-phase fraction ≥8%, aneuploidy, and p53 overexpression was 8, 14, and 8 and times higher, respectively. However, in a multivariable regression model, adjusted for stage, grade, and age, S-phase fraction, DNA ploidy, and p53 were not statistically independent prognostic factors (p=0.413, p=0.107, p=0.208, respectively) for 5-year relative survival in stage I–III grade 1–3 endometrioid endometrial carcinoma. In a subgroup analysis of stage I grade 1–2, aneuploidy identified a subgroup with impaired 5-year relative survival.ConclusionWe can conclude that S-phase fraction, DNA ploidy, and p53 overexpression did not improve identification of high-risk patients by stage, grade, and age in stage I–III endometrioid endometrial carcinoma. In stage I, aneuploidy and grade 2 predicted lower relative survival rates than other variables.

Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma

“…In a multivariable analysis using the fourth quartile as cut off, a trend but no significance was obtained. Only a few studies have analyzed S-phase in larger patient cohorts [11,23,24]. These reports have shown SPF as prognostic factor in simple analysis in concordance with the results in our study.…”

“…However, these results were not seen in other reports [19][20][21][22][23]. Even when focusing on the larger studies, there are conflicting results where ploidy was of prognostic importance in some [7,15,30] and not in others [11,18,23,31]. The interpretation of the results is difficult as many studies include patients with higher FIGO stages and different tumor types.…”

“…Several studies on women with endometrial carcinoma have found aneuploidy as a negative prognostic factor in multivariable analysis [7][8][9][10][11][12][13][14][15][16][17] and also as the strongest prognostic factor [18]. However, these results were not seen in other reports [19][20][21][22][23]. Even when focusing on the larger studies, there are conflicting results where ploidy was of prognostic importance in some [7,15,30] and not in others [11,18,23,31].…”

“…In our study, only women with FIGO stage I endometrioid endometrial carcinomas were included. In a recent Swedish study, Svanvik et al [23] analyzed stage I-III endometrial carcinoma. In their cohort, ploidy was no prognostic factor in multivariable analysis but they were unfortunately not able to analyze the excess mortality in multivariable analysis for FIGO stage I endometrioid endometrial carcinomas since there were no overall risk among these patients.…”