Utility of HE4 to identify patients with endometrioid endometrial cancer who may require lymphadenectomy

Dobrzycka, Bożena; Maćkowiak-Matejczyk, Beata; Terlikowska, Katarzyna M.; Kinalski, Maciej; Terlikowski, S

doi:10.1016/j.advms.2015.07.010

Cited by 17 publications

(25 citation statements)

References 39 publications

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“…While the histological grading of the neoplasia is deemed to have major impact in stratifying patients into “risk classes”, we have to highlight its marginal role in classifying patients in early (FIGO I) versus advanced (FIGO > I) stage. In contrast with the literature 12 , 30 , 31 , in the current analysis its impact on the probability of being surgically staged as advanced (FIGO > I) is very low. Noteworthy, in both the whole and in the endometrioid series, the impact of tumor grade is very lower compared to BMI and age, and a little bit lower compared to number of children.…”

Section: Discussioncontrasting

confidence: 93%

“…In several studies, preoperative sHE4 and sCA125 values were correlated with myometrium invasion, tumor grade and cervical invasion 12 , 30 , 31 to identify high risk EC patients who may require lymphadenectomy. While the histological grading of the neoplasia is deemed to have major impact in stratifying patients into “risk classes”, we have to highlight its marginal role in classifying patients in early (FIGO I) versus advanced (FIGO > I) stage.…”

Section: Discussionmentioning

confidence: 99%

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RERT: A Novel Regression Tree Approach to Predict Extrauterine Disease in Endometrial Carcinoma Patients

Vezzoli

Ravaggi

Zanotti

et al. 2017

Sci Rep

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Some aspects of endometrial cancer (EC) preoperative work-up are still controversial, and debatable are the roles played by lymphadenectomy and radical surgery. Proper preoperative EC staging can help design a tailored surgical treatment, and this study aims to propose a new algorithm able to predict extrauterine disease diffusion. 293 EC patients were consecutively enrolled, and age, BMI, children’s number, menopausal status, contraception, hormone replacement therapy, hypertension, histological grading, clinical stage, and serum HE4 and CA125 values were preoperatively evaluated. In order to identify before surgery the most important variables able to classify EC patients based on FIGO stage, we adopted a new statistical approach consisting of two-steps: 1) Random Forest with its relative variable importance; 2) a novel algorithm able to select the most representative Regression Tree (RERT) from an ensemble method. RERT, built on the above mentioned variables, provided a sensitivity, specificity, NPV and PPV of 90%, 76%, 94% and 65% respectively, in predicting FIGO stage > I. Notably, RERT outperformed the prediction ability of HE4, CA125, Logistic Regression and single cross-validated Regression Tree. Such algorithm has great potential, since it better identifies the true early-stage patients, thus providing concrete support in the decisional process about therapeutic options to be performed.

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Section: Discussioncontrasting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

RERT: A Novel Regression Tree Approach to Predict Extrauterine Disease in Endometrial Carcinoma Patients

Vezzoli

Ravaggi

Zanotti

et al. 2017

Sci Rep

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“…Similarly to Abdalla et al18 and Dobrzycka et al,19 we observed no differences in HE4 levels between the subgroups of patients with well- and moderately differentiated endometrial tumors while observing statistically significant differences between the subgroups of patients with well- and poorly differentiated endometrial tumors.…”

Section: Discussionsupporting

confidence: 87%

Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients

Cymbaluk‐Płoska¹,

Chudecka‐Głaz²,

Pius-Sadowska

et al. 2017

OTT

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IntroductionEndometrial cancer is the one of the most common cancers of the genital organ. HE4 and MMP2 are both proteins whose serum levels increase in endometrial cancer.AimTo explore the diagnostic potential of the serum levels of HE4 and MMP2 in patients with endometrial cancer and benign endometrial diseases. To assess the relationship between the serum levels of HE4 and MMP2 and the typical prognostic factors in patients with endometrial cancer.Materials and methodsIncluded in the study was a group of 112 patients presenting with bleeding abnormalities at the Pomeranian Medical University in years 2012–2016. Serum HE4 concentrations were measured using the Elecsys Electrochemiluminescence Immunoassay (ECLIA). MMP2 concentrations were quantified in the serum using multiplex immunoassays.ResultsWe observed statistically significant differences in mean serum levels of HE4 and MMP2 between the group of endometrial cancer patients and the group of patients with no changes in the endometrium (P=0.002/0.003). The diagnostic potential of HE4 and MMP2 in differentiation of high (International Federation of Gynecology and Obstetrics [FIGO] III and IV) vs low (FIGO I and II) clinical stage of tumor and prediction of cellular differentiation grade (G1 vs G3) on the basis of the analysis of the area under the curve is, respectively, 0.86 and 0.82 for HE4 and 0.82 and 0.74 for MMP2. The HE4 marker was significantly more specific than MMP2 in every study group and amounted to 93% vs 86% in all patients included in the analysis, 94% vs 84% in pre-menopausal patients and 84% vs 79% in post-menopausal patients.ConclusionHE4 and MMP2 are characterized by high specificity and may be useful as biomarkers in the diagnostics of endometrial cancer. When determined preoperatively, HE4 is correlated with the prognostic factors of endometrial cancer and may be helpful in the planning of individual treatment of endometrial cancer patients.

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“…In our recent study we showed that in the early stage of endometrioid endometrial cancer, HE4 can serve as a preoperative tool that can help to identify postmenopausal women who may require lymphadenectomy [ 27 ]. The present study aimed at evaluating and comparing the role of HE4, CA125 and ROMA value for the differential diagnosis of epithelial ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Preoperative HE4, CA125 and ROMA in the differential diagnosis of benign and malignant adnexal masses

et al. 2016

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BackgroundThe aim of this study was to evaluate HE4, CA125 and ROMA in the preoperative differentiation benign ovarian diseases from epithelial ovarian cancer depending on the menopausal status.MethodsIn order to estimate markers’ concentrations in the serum of women with benign ovarian disease (n = 128) and with epithelial ovarian carcinoma (n = 96) the electrochemiluminescence (ECLIA) technique has been applied.ResultsUsing the ROC analysis, although no statistical differences were found among their AUCs, the ROMA algorithm seems to be effective in gathering the diverse performance of HE4 and CA125. The AUC for HE4, CA125 and ROMA for all patients were: 0.895; 0.879 and 0.918, respectively. At established new optimal cutoff values for HE4, CA125 and ROMA we found higher specificity in postmenopausal compared to premenopausal women (96.9 vs 89.8 % and 97.7 vs 84.1 % and 95.9 vs 89.1 %, respectively). The sensitivity of HE4 in pre- and postmenopausal women was similar (83.5 vs 83.8 %), while for CA125 was the highest in premenopausal women (87.0 vs 84.1 %). For HE4, CA125 and ROMA the negative predictive value was high (97.6, 93.9 and 94.4 %, respectively).ConclusionsThe ROMA algorithm shows the best diagnostic performance to distinguish epithelial ovarian cancer from benign ovarian disease. We found the high specificity of HE4 and CA125 while differentiating ovarian benign diseases from epithelial ovarian cancer in postmenopausal women and the high sensitivity of CA125 in detecting epithelial ovarian cancer in premenopausal patients.

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Utility of HE4 to identify patients with endometrioid endometrial cancer who may require lymphadenectomy

Cited by 17 publications

References 39 publications

RERT: A Novel Regression Tree Approach to Predict Extrauterine Disease in Endometrial Carcinoma Patients

RERT: A Novel Regression Tree Approach to Predict Extrauterine Disease in Endometrial Carcinoma Patients

Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients

Preoperative HE4, CA125 and ROMA in the differential diagnosis of benign and malignant adnexal masses

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