Predictive value of serum <scp>HE</scp>4 and <scp>CA</scp>125 concentrations for lymphatic metastasis of endometrial cancer

Wang, Yingmei; Han, Choong‐Hee; Teng, Fei; Bai, Zhaoyi; Tian, Wenyan; Xue, Fengxia

doi:10.1002/ijgo.12010

Cited by 40 publications

(65 citation statements)

References 22 publications

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“…One additional article was identified by extensive cross‐checking of the reference lists . Ten studies were analyzed multiple times because they included two or three biomarkers . The agreement of the two reviewers (C.R.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic Accuracy of Clinical Biomarkers for Preoperative Prediction of Lymph Node Metastasis in Endometrial Carcinoma: A Systematic Review and Meta-Analysis

et al. 2019

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Background In endometrial carcinoma (EC), preoperative classification is based on histopathological criteria, with only moderate diagnostic performance for the risk of lymph node metastasis (LNM). So far, existing molecular classification systems have not been evaluated for prediction of LNM. Optimized use of clinical biomarkers as recommended by international guidelines might be a first step to improve tailored treatment, awaiting future molecular biomarkers. Aim To determine the diagnostic accuracy of preoperative clinical biomarkers for the prediction of LNM in endometrial cancer. Methods A systematic review was performed according to the Meta‐analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Studies identified in MEDLINE and EMBASE were selected by two independent reviewers. Included biomarkers were based on recommended guidelines (cancer antigen 125 [Ca‐125], lymphadenopathy on magnetic resonance imaging, computed tomography, and 18F‐fluorodeoxyglucose positron emission tomography/computed tomography [18FDG PET‐CT]) or obtained by physical examination (body mass index, cervical cytology, blood cell counts). Pooled sensitivity, specificity, area under the curve (AUC), and likelihood ratios were calculated with bivariate random‐effects meta‐analysis. Likelihood ratios were classified into small (0.5–1.0 or 1–2.0), moderate (0.2–0.5 or 2.0–5.0) or large (0.1–0.2 or ≥ 5.0) impact. Results Eighty‐three studies, comprising 18,205 patients, were included. Elevated Ca‐125 and thrombocytosis were associated with a moderate increase in risk of LNM; lymphadenopathy on imaging with a large increase. Normal Ca‐125, cytology, and no lymphadenopathy on 18FDG PET‐CT were associated with a moderate decrease. AUCs were above 0.75 for these biomarkers. Other biomarkers had an AUC <0.75 and incurred only small impact. Conclusion Ca‐125, thrombocytosis, and imaging had a large and moderate impact on risk of LNM and could improve preoperative risk stratification. Implications for Practice Routine lymphadenectomy in clinical early‐stage endometrial carcinoma does not improve outcome and is associated with 15%–20% surgery‐related morbidity, underlining the need for improved preoperative risk stratification. New molecular classification systems are emerging but have not yet been evaluated for the prediction of lymph node metastasis. This article provides a robust overview of diagnostic performance of all clinical biomarkers recommended by international guidelines. Based on these, at least measurement of cancer antigen 125 serum level, assessment of thrombocytosis, and imaging focused on lymphadenopathy should complement current preoperative risk stratification in order to better stratify these patients by risk.

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Section: Resultsmentioning

confidence: 99%

Diagnostic Accuracy of Clinical Biomarkers for Preoperative Prediction of Lymph Node Metastasis in Endometrial Carcinoma: A Systematic Review and Meta-Analysis

et al. 2019

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“…Remarkably, in EC, serum WFDC2 reported a significantly higher pooled sensitivity (0.71) in comparison to MUC16 (0.35) and has been demonstrated to be a better diagnostic tool [49]. WFDC2 has also been demonstrated to be a more sensible predictor of lymph node metastasis (sensitivity of 0.82) in relation to MUC16 (0.72) [50] and better in predicting myometrial invasion (AUC of 0.76) than MUC16 (AUC = 0.65) [12].…”

Section: Prognostic Protein Biomarkers In Ecmentioning

confidence: 97%

“…Notably, MKI67 and PTEN were also validated in tissue samples from imprint smears [51][52][53], as well as CDH1, which was analyzed in uterine aspirates using mass spectrometry-based approaches [54]. MUC16 and WFDC2 have been extensively studied in serum samples by antibody-based techniques such as ELISA or chemiluminescence techniques [50,[55][56][57] and L1CAM was also validated in serum but just in one study [58].…”

Section: Prognostic Protein Biomarkers In Ecmentioning

confidence: 99%

Prognostic Biomarkers in Endometrial Cancer: A Systematic Review and Meta-Analysis

Rubia

Martínez‐García

Dittmar

et al. 2020

JCM

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Endometrial cancer (EC) is the sixth most common cancer in women worldwide and its mortality is directly associated with the presence of poor prognostic factors driving tumor recurrence. Stratification systems are based on few molecular, and mostly clinical and pathological parameters, but these systems remain inaccurate. Therefore, identifying prognostic EC biomarkers is crucial for improving risk assessment pre- and postoperatively and to guide treatment decisions. This systematic review gathers all protein biomarkers associated with clinical prognostic factors of EC, recurrence and survival. Relevant studies were identified by searching the PubMed database from 1991 to February 2020. A total number of 398 studies matched our criteria, which compiled 255 proteins associated with the prognosis of EC. MUC16, ESR1, PGR, TP53, WFDC2, MKI67, ERBB2, L1CAM, CDH1, PTEN and MMR proteins are the most validated biomarkers. On the basis of our meta-analysis ESR1, TP53 and WFDC2 showed potential usefulness for predicting overall survival in EC. Limitations of the published studies in terms of appropriate study design, lack of high-throughput measurements, and statistical deficiencies are highlighted, and new approaches and perspectives for the identification and validation of clinically valuable EC prognostic biomarkers are discussed.

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“…Currently, the role of biomarkers in EC has not been clearly defined. CA125 is one of the most commonly used biomarkers, but it lacks sensitivity and specificity for detection and predicting prognoses [ 4 – 6 ]. Aldehyde dehydrogenase 1 (ALDH1) is a predominant isoform of the ALDH family in mammals, and it has recently been reported as a novel marker in gynecologic cancer.…”

Section: Introductionmentioning

confidence: 99%

The combination of aldehyde dehydrogenase 1 (ALDH1) and CD44 is associated with poor outcomes in endometrial cancer

et al. 2018

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Aldehyde dehydrogenase 1 (ALDH1) and CD44 have been established as biomarkers for predicting the survival of many types of cancer patients. This study evaluated the expression and clinical significance of these putative cancer-cell markers in a series of tumor samples from endometrial cancer (EC) patients using tissue microarray. We examined 245 endometrial samples, including 132 (53.87%) pre-malignancy lesions and 113 (46.12%) malignant endometrial lesions from biopsies or hysterectomies. We examined the expression of CD44 and ALDH1 in these samples using immunohistochemistry staining. Correlations in the relative expression of these markers with clinicopathological parameters were also assessed. A high level of expression of ALDH1 was found in 44.25% (50/113) of the endometrial cancer samples, which was significantly correlated with a poor overall survival rate (p = 0.035). High-level CD44 expression was found in 35.4% (40/113) of the cases and was also correlated with a poor overall survival rate (p = 0.035). A simultaneous high expression of both markers was correlated with an extremely poor overall survival (p = 0.013). Our results show that tumors with higher expressions of both ALDH1 and CD44 were related to a poorer overall survival rate among EC patients. The combination of ALDH1 and CD44 could be a promising marker for developing additional targeted therapy for severe endometrial cancers.

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Predictive value of serum HE4 and CA125 concentrations for lymphatic metastasis of endometrial cancer

Abstract: The combined evaluation of serum HE4 and CA125 could provide gynecologic oncologists with improved information to guide the decision of whether to perform lymphadenectomy.

Cited by 40 publications

References 22 publications

Diagnostic Accuracy of Clinical Biomarkers for Preoperative Prediction of Lymph Node Metastasis in Endometrial Carcinoma: A Systematic Review and Meta-Analysis

Diagnostic Accuracy of Clinical Biomarkers for Preoperative Prediction of Lymph Node Metastasis in Endometrial Carcinoma: A Systematic Review and Meta-Analysis

Prognostic Biomarkers in Endometrial Cancer: A Systematic Review and Meta-Analysis

The combination of aldehyde dehydrogenase 1 (ALDH1) and CD44 is associated with poor outcomes in endometrial cancer

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