Dataset Information

AKR1B1 and AKR1B10 as Prognostic Biomarkers of Endometrioid Endometrial Carcinomas.

ABSTRACT: The roles of aldo-keto reductase family 1 member B1 (AKR1B1) and B10 (AKR1B10) in the pathogenesis of many cancers have been widely reported but only briefly studied in endometrial cancer. To clarify the potential of AKR1B1 and AKR1B10 as tissue biomarkers of endometrial cancer, we evaluated the immunohistochemical levels of AKR1B1 and AKR1B10 in tissue paraffin sections from 101 well-characterized patients with endometrioid endometrial cancer and 12 patients with serous endometrial cancer and compared them with the clinicopathological data. Significantly higher immunohistochemical levels of AKR1B1 and AKR1B10 were found in adjacent non-neoplastic endometrial tissue compared to endometrioid endometrial cancer. A trend for better survival was observed in patients with higher immunohistochemical AKR1B1 and AKR1B10 levels. However, no statistically significant differences in overall survival or disease-free survival were observed when AKR1B1 or AKR1B10 were examined individually in endometrioid endometrial cancer. However, analysis of AKR1B1 and AKR1B10 together revealed significantly better overall and disease-free survival in patients with both AKR1B1 and AKR1B10 staining above the median values compared to all other patients. Multivariant Cox analysis identified strong AKR1B1 and AKR1B10 staining as a statistically important survival prediction factor. Conversely, no significant differences were found in serous endometrial cancer. Our results suggest that AKR1B1 and AKR1B10 play protective roles in endometrioid endometrial cancer and show potential as prognostic biomarkers.

SUBMITTER: Hojnik M

PROVIDER: S-EPMC8305663 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Our aim was to investigate whether molecular classification can be used to refine prognosis in grade 3 endometrial endometrioid carcinomas (EECs). Grade 3 EECs were classified into 4 subgroups: p53 abnormal, based on mutant-like immunostaining (p53abn); MMR deficient, based on loss of mismatch repair protein expression (MMRd); presence of POLE exonuclease domain hotspot mutation (POLE); no specific molecular profile (NSMP), in which none of these aberrations were present. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method (Log-rank test) and univariable and multivariable Cox proportional hazard models. In total, 381 patients were included. The median age was 66 years (range, 33 to 96?y). Federation Internationale de Gynecologie et d'Obstetrique stages (2009) were as follows: IA, 171 (44.9%); IB, 120 (31.5%); II, 24 (6.3%); III, 50 (13.1%); IV, 11 (2.9%). There were 49 (12.9%) POLE, 79 (20.7%) p53abn, 115 (30.2%) NSMP, and 138 (36.2%) MMRd tumors. Median follow-up of patients was 6.1 years (range, 0.2 to 17.0?y). Compared to patients with NSMP, patients with POLE mutant grade 3 EEC (OS: hazard ratio [HR], 0.36 [95% confidence interval, 0.18-0.70]; P=0.003; RFS: HR, 0.17 [0.05-0.54]; P=0.003) had a significantly better prognosis; patients with p53abn tumors had a significantly worse RFS (HR, 1.73 [1.09-2.74]; P=0.021); patients with MMRd tumors showed a trend toward better RFS. Estimated 5-year OS rates were as follows: POLE 89%, MMRd 75%, NSMP 69%, p53abn 55% (Log rank P=0.001). Five-year RFS rates were as follows: POLE 96%, MMRd 77%, NSMP 64%, p53abn 47% (P=0.000001), respectively. In a multivariable Cox model that included age and Federation Internationale de Gynecologie et d'Obstetrique stage, POLE and MMRd status remained independent prognostic factors for better RFS; p53 status was an independent prognostic factor for worse RFS. Molecular classification of grade 3 EECs reveals that these tumors are a mixture of molecular subtypes of endometrial carcinoma, rather than a homogeneous group. The addition of molecular markers identifies prognostic subgroups, with potential therapeutic implications.

Dataset Information

AKR1B1 and AKR1B10 as Prognostic Biomarkers of Endometrioid Endometrial Carcinomas.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets