Utility of human epididymis protein 4 serum marker for the detection of adnexal malignancy: a multicentric prospective study

Zapardiel, Ignacio; Gorostidi, Mikel; Ravaggi, Antonella; Allende, M.T.; Silveira, Margarida; Macuks, Ronalds

doi:10.1097/cej.0000000000000259

Cited by 9 publications

(5 citation statements)

References 25 publications

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“…Taken collectivity with the notion showing that SPON1 is a secreted protein, it is reasonable that SPON1 could be used as a serum biomarker for ovarian cancer and STIC. The utility of SPON1 alone or together with CA-125 [ 20 – 27 ] and/or Human epididymis protein 4 (HE4) [ 22 , 28 ] should be determined in future experiments using serum samples from patients with ovarian cancer, other benign and malignant tumors, as well as samples from healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

SPON1 is an independent prognostic biomarker for ovarian cancer

et al. 2023

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Background Ovarian cancer has the worst outcome among gynecological malignancies; therefore, biomarkers that could contribute to the early diagnosis and/or prognosis prediction are urgently required. In the present study, we focused on the secreted protein spondin-1 (SPON1) and clarified the prognostic relevance in ovarian cancer. Methods We developed a monoclonal antibody (mAb) that selectively recognizes SPON1. Using this specific mAb, we determined the expression of SPON1 protein in the normal ovary, serous tubal intraepithelial carcinoma (STIC), and ovarian cancer tissues, as well as in various normal adult tissues by immunohistochemistry, and verified its clinicopathological significance in ovarian cancer. Results The normal ovarian tissue was barely positive for SPON1, and no immunoreactive signals were detected in other healthy tissues examined, which was in good agreement with data obtained from gene expression databases. By contrast, upon semi-quantification, 22 of 242 ovarian cancer cases (9.1%) exhibited high SPON1 expression, whereas 64 (26.4%), 87 (36.0%), and 69 (28.5%) cases, which were designated as SPON1-low, possessed the moderate, weak, and negative SPON1 expression, respectively. The STIC tissues also possessed SPON1-positive signals. The 5-year recurrence-free survival (RFS) rate in the SPON1-high group (13.6%) was significantly lower than that in the SPON1-low group (51.2%). In addition, high SPON1 expression was significantly associated with several clinicopathological variables. Multivariable analysis revealed that high SPON1 was an independent prognostic factor for RFS of ovarian cancer. Conclusions SPON1 represents a prognostic biomarker for ovarian cancer, and the anti-SPON1 mAb could be valuable as an outcome predictor.

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Section: Discussionmentioning

confidence: 99%

SPON1 is an independent prognostic biomarker for ovarian cancer

et al. 2023

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“…In the last decade, the human epididymis protein 4 (HE4) biomarker has shown higher specificity than CA125 (0.93 vs 0.75, respectively), and improved the detection of malignancy in patients with adnexal masses. 9–12 HE4 levels are not affected by the menstrual cycle, hormonal treatment, or endometriosis. 13 Therefore, HE4 could be a helpful tumor marker in patients with endometriosis and suspected malignancy as an add-on assessment to ultrasonography.…”

Section: Introductionmentioning

confidence: 89%

HE4 might be a more useful tumor biomarker to detect malignancy in patients with ovarian endometrioma when malignancy is suspected

et al. 2021

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Objective To analyze the utility of carbohydrate antigen (CA)125 and human epididymis protein 4 (HE4) to detect malignancy in women with ovarian endometriosis, when ovarian cancer is suspected and ultrasonography results are inconclusive. Methods Women who underwent surgery between 2015 and 2019 for ovarian endometriosis or for adnexal masses, with a final diagnosis of ovarian carcinoma (clear cell and endometrioid) were included in this retrospective study. The women were divided into three groups: ovarian endometriosis (OE), ovarian carcinoma without endometriosis (OC), and ovarian carcinoma with endometriosis (OC + E). Adnexal masses were assessed preoperatively by transvaginal ultrasonography according to the International Ovarian Tumor Analysis (IOTA) simple rules, and CA125 and HE4 blood levels were obtained. Results Of 208 women, 45 had malignancy, 16 in the OC + E group and 29 in the OC group. According to transvaginal ultrasonography, 13 were classified as undetermined risk of malignancy: OC group: 3, OE group: 3, and OC + E group: 7. When we compared the tumor biomarkers, significant differences in HE4 but not in CA125 levels were found between the groups. Conclusions When ovarian malignancy is suspected in patients with ovarian endometriosis, HE4 is a more useful tumor biomarker to diagnose OC when ultrasonography results are inconclusive.

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“…Human epididymis protein 4 (HE4) levels are not elevated in benign diseases, such as endometriosis, and are not affected by the menstrual cycle or hormone therapy. HE4 also has higher specificity than CA-125 (0.93 vs. 0.75, respectively) ( 77 , 78 ). Hence, HE4 could be useful in distinguishing suspected malignant ovarian tumors from endometriosis.…”

Section: A Promising Tool For the Early Diagnosis Of Malignant Transf...mentioning

confidence: 99%

Clinicopathological characteristics, molecular features and novel diagnostic strategies for the detection of malignant transformation of endometriosis (Review)

Kobayashi

2023

Exp Ther Med

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Endometriosis is a benign gynecological disease that affects women of reproductive age. Although malignant transformation of endometriosis is rare, physicians must be aware of this due to the high incidence of clear cell carcinoma of the ovary (CCC) in Japan. The most prevalent histological subtype of ovarian cancer is CCC (~70%) followed by endometrioid carcinoma (30%). The present review discusses the clinicopathological and molecular features of endometriosis-associated ovarian cancer (EAOC) as well as prospects for novel diagnostic strategies. Papers published between 2000 and 2022 in the PubMed and Google Scholar databases were included. Contents of the endometriotic cyst fluid may be involved in carcinogenesis, although the underlying mechanisms are largely unknown. Some studies have proposed a possible mechanism wherein excessive hemoglobin, heme and iron could cause an imbalance in intracellular redox homeostasis in endometriotic cells. Combined with DNA damage and mutations, the imbalances may induce the development of EAOC. Endometriotic cells evolve to adapt to the prolonged unfavorable oxidative microenvironmental stress. On the other hand, macrophages enhance the antioxidative defense mechanism and protect endometriotic cells against oxidative damage through intercellular crosstalk and signaling pathways. Therefore, changes in redox signaling, energy metabolism and the tumor immune microenvironment could be the key elements in the malignant transformation of certain endometriotic cell clones. Additionally, non-invasive bioimaging (i.e., magnetic resonance relaxometry) and biomarkers (i.e., tissue factor pathway inhibitor 2) may be promising tools for early-stage detection of the disease. In conclusion, the present review summarizes the latest advancements in research on the biological characteristics and early diagnosis of malignant transformation of endometriosis. Contents 1. Introduction 2. Literature search 3. Current understanding of malignant transformation of endometriosis 4. A promising tool for the early diagnosis of malignant transformation of endometriosis 5. Discussion and future challenges HIROSHI KOBAYASHI 1,2

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Utility of human epididymis protein 4 serum marker for the detection of adnexal malignancy: a multicentric prospective study

Cited by 9 publications

References 25 publications

SPON1 is an independent prognostic biomarker for ovarian cancer

SPON1 is an independent prognostic biomarker for ovarian cancer

HE4 might be a more useful tumor biomarker to detect malignancy in patients with ovarian endometrioma when malignancy is suspected

Clinicopathological characteristics, molecular features and novel diagnostic strategies for the detection of malignant transformation of endometriosis (Review)

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