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DNA ploidy in curettage specimens identifies high-risk patients and lymph node metastasis in endometrial cancer.

ABSTRACT: Preoperative risk stratification is essential in tailoring endometrial cancer treatment, and biomarkers predicting lymph node metastasis and aggressive disease are aspired in clinical practice. DNA ploidy assessment in hysterectomy specimens is a well-established prognostic marker. DNA ploidy assessment in preoperative curettage specimens is less studied, and in particular in relation to the occurrence of lymph node metastasis.Curettage image cytometry DNA ploidy in relation to established clinicopathological variables and outcome was investigated in 785 endometrial carcinoma patients prospectively included in the MoMaTEC multicentre trial.Diploid curettage status was found in 72.0%, whereas 28.0% were non-diploid. Non-diploid status significantly correlated with traditional aggressive postoperative clinicopathological features, and was an independent predictor of lymph node metastasis among FIGO stage I-III patients in multivariate analysis (OR 1.94, P=0.033). Non-diploid status was related to shorter disease-specific survival (5-year DSS of 74.4% vs 88.8% for diploid curettage, P<0.001). When stratifying by FIGO stage and lymph node status, the prognostic effect remained. However, in multivariate regression analysis, preoperative histological risk classification was a stronger predictor of DSS than DNA ploidy.Non-diploid curettage is significantly associated with aggressive clinicopathological phenotype, lymph node metastasis, and poor survival in endometrial cancer. The prognostic effect was also observed among subgroups with (presumably) less aggressive traits, such as low FIGO stage and negative lymph node status. Our results indicate curettage DNA ploidy as a possible supplement to existing parameters used to tailor surgical treatment.

SUBMITTER: Njolstad TS

PROVIDER: S-EPMC4430715 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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DNA ploidy in curettage specimens identifies high-risk patients and lymph node metastasis in endometrial cancer.

Njølstad T S TS Trovik J J Hveem T S TS Kjæreng M L ML Kildal W W Pradhan M M Marcickiewicz J J Tingulstad S S Staff A C AC Haugland H K HK Eraker R R Oddenes K K Rokne J A JA Tjugum J J Lode M S MS Amant F F Werner H M HM Salvesen H B HB Danielsen H E HE

British journal of cancer 20150421 10

<h4>Background</h4>Preoperative risk stratification is essential in tailoring endometrial cancer treatment, and biomarkers predicting lymph node metastasis and aggressive disease are aspired in clinical practice. DNA ploidy assessment in hysterectomy specimens is a well-established prognostic marker. DNA ploidy assessment in preoperative curettage specimens is less studied, and in particular in relation to the occurrence of lymph node metastasis.<h4>Methods</h4>Curettage image cytometry DNA ploi ...[more]

PMID: 25897678

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Project description:BackgroundIn recent years, sentinel lymph node excision and ultrastaging have been performed in endometrial carcinomas to obtain information about lymph node status, avoiding unnecessary complete pelvic and paraaortic lymphadenectomy. The purpose of this retrospective study was to provide a comprehensive evaluation of the pathological features of endometrial carcinomas and their significance in association with sentinel lymph node involvement.MethodsPatients with endometrial carcinomas, preceded by sentinel lymph node mapping, were classified into Group-I and Group-II with negative and positive involvement, respectively. The pathological features, associated with sentinel lymph node involvement, were statistically analyzed, including determination of test performance parameters.ResultsAmong 70 patients who had undergone hysterectomy and sentinel lymph node excision, 61 had carcinoma and 9 had atypical hyperplasia. There were 50 patients in Group-I and 10 in Group-II. In Group-II, the significant pathological features were: 1) lower uterine segment involvement (100%), 2) an average tumor size of ≥5 CM, 3) lymphovascular invasion (50%), 4) cervical stromal invasion (40%), and 5) depth of myometrial invasion of ≥50% (50%). The incidences of these pathological features were significantly less in Group-I. Statistical analyses singled out "lower uterine segment involvement" as the most important feature.ConclusionsWe have identified five pathological features which are associated with sentinel lymph node involvement. Since lower uterine segment involvement has occurred in all cases of the Group-II cohort, we recommend FIGO and other organizations that determine staging rules should consider whether tumors that involve the lower uterine segment should be staged as higher than "1a", if the findings in this small series are confirmed by other studies. The results of this study may guide pathologists and oncologists in the diagnostic and therapeutic approaches to management of endometrial carcinomas.

Project description:BackgroundLymph node metastasis (LNM) is an important prognostic factor in endometrial cancer. Anomalous microRNAs (miRNAs) are associated with cell functions and are becoming a powerful tool to characterize malignant transformation and metastasis. The aim of this study was to construct a miRNA signature to predict LNM in endometrial endometrioid carcinoma (EEC).MethodCandidate target miRNAs related to LNM in EEC were screened by three methods including differentially expressed miRNAs (DEmiRs), weighted gene co-expression network analysis (WGCNA), and decision tree algorithms. Samples were randomly divided into the training and validation cohorts. A miRNA signature was built using a logistic regression model and was evaluated by the area under the curve (AUC) of receiver operating characteristic curve (ROC) and decision curve analysis (DCA). We also conducted pathway enrichment analysis and miRNA-gene regulatory network to look for potential genes and pathways engaged in LNM progression. Survival analysis was performed, and the miRNAs were tested whether they expressed differently in another independent GEO database.ResultThirty-one candidate miRNAs were screened and a final 15-miRNA signature was constructed by logistic regression. The model showed good calibration in the training and validation cohorts, with AUC of 0.824 (95% CI, 0.739-0.912) and 0.821 (95% CI, 0.691-0.925), respectively. The DCA demonstrated the miRNA signature was clinically useful. Hub miRNAs in signature seemed to contribute to EEC progression via mitotic cell cycle, cellular protein modification process, and molecular function. MiR-34c was statistically significant in survival that a higher expression of miR-34c indicated a higher survival time. MiR-34c-3p, miR-34c-5p, and miR-34b-5p were expressed differentially in GSE75968.ConclusionThe miRNA signature could work as a noninvasive method to detect LNM in EEC with a high prediction accuracy. In addition, miR-34c cluster may be a key biomarker referring LNM in endometrial cancer.

Dataset Information

DNA ploidy in curettage specimens identifies high-risk patients and lymph node metastasis in endometrial cancer.

Publications

DNA ploidy in curettage specimens identifies high-risk patients and lymph node metastasis in endometrial cancer.

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