Erratum: HE4 is a novel tissue marker for therapy response and progestin resistance in medium- and low-risk endometrial hyperplasia

Ørbo, Anne; Arnes, Marit; Lyså, Lena Myreng; Borgfeldt, Christer; Straume, Bjørn

doi:10.1038/bjc.2016.330

Cited by 5 publications

(9 citation statements)

References 38 publications

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“…The fact of menopause development in the Odesa region at the age of 47.6 years (according to the City Center for Menopause, 2005) coincides with the maximum period of detection of hyperplastic and atypical forms of endometrium proliferative states. It has been established that simple and complex atypical hyperplasia are results of relative or absolute estrogen hyper-secretion, and atypical forms are progressive monoclonal muta-tional damage with hormone-independent local growth [3,22,25].…”

Section: Study Results and Discussionmentioning

confidence: 99%

“…It is interesting that results of this study established AH in all age groups, starting from 18 years, with different frequency of manifestation. Atypical forms of hyperplasia are malignant from 8% to 44% [3,25] and are relevant for development of solutions for cancer prevention from a morphological point of view. No malignancy was found in the age group up to 46 years, possibly due to the influence of certain protection factors.…”

Section: Study Results and Discussionmentioning

confidence: 99%

“…This period is considered the "perimenopausal estrogen window", or the period of "uncovered" estrogenic effects on the endometrium. It is from this age that the fact of increasing the frequency of adenocarcinoma begins [1,12,23,25].…”

Section: Study Results and Discussionmentioning

confidence: 99%

“…It is known that in physiological conditions, as a result of apoptosis, only damaged cells are released, which is leading in the process of protecting the body from malignancy [3,9]. It has been hypothesized that cell ageing is a Years manifestation of protection against the division of genetically damaged cells and the transition to neoplasia [6,25]. Stopping mitosis in cells that have reached the Hayflick limit causes activation of p53 [9,10], p53 protein is expressed in all cell types as an inactive latent transcription factor, only during stress exposure -DNA damage, oxidative stress, telomere shortening, oncogenes activation p53 activation occurs and apoptosis as a consequence [8,9,13].…”

Section: Study Results and Discussionmentioning

confidence: 99%

“…There is an increase in the occurrence of atypical EHP and EC in the reproductive period, which encourages researchers to carry out a program of cancer prevention and development of early diagnostic markers, treatment measures on the background of various morphological aspects [13,20,23]. Proliferative processes of the endometrium can mimic the periodic cycle normalization with prospect of recurrence and malignancy, and in some cases regression of pathology; such multifactorial processes depend on the manifestation of pathohistological changes and general characteristics of the body as a whole, and requires further study of etiopathogenetic mechanisms nature and possible early markers of development prospects search [2,24,25].…”

Section: Introductionmentioning

confidence: 99%

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The retrospective analysis results of the endometrial tissue pathological conditions development

Artyomenko

Chumak

Shapoval

2020

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Hyperplastic processes of endometrium are one of the most common pathologies of the uterus mucosa, an interest in its study is due to an increase in the frequency of occurrence, the ability to both self-healing and malignancy.Purpose of the study: to investigate the detection rate of endometrial proliferative changes depending on the age of woman.Materials and methods. A retrospective medical documentation analysis of the Department of Pathology was conducted. 2196 pathologic findings of endometrial tissue samples were investigated. 1404 specimen were hyperplastic states, 688 were endometrial polyps, and 104 others were endometrial states after total or subtotal uterine removal after surgery. Histological conditions were distributed according to patients’ age categories. Results of the study were processed statistically using variation statistics with Student's criterion, using standard computer systems.Results. The analysis shows an increase in frequency of endometrial proliferative changes in perimenopausal patients on the background of endometrial pathological changes detection in all age categories. Atypical forms of simple and complex hyperplasia of the endometrium can be traced in all age categories, with a maximum frequency of manifestation in similar age-related periods – 41–45 years and 46–50 years. Morphological signs of endometrial tissue malignancy were first established in the age group of 46–50 years, which coincides with the age of the onset of menopause in the Odesa region, with subsequent relative increase in the frequency and aggressiveness of the process with age. These age groups focus doctors to be more careful about pathological manifestations.Conclusion. As a result of retrospective analysis of histopathological examinations it was found that the main factor in detecting pathological conditions of the endometrium is a woman's age of perimenopausal period, which can be considered as an early marker of diagnosis, leading to treatment prospects and general therapeutic tactics, for the future diagnostics and detection of others immunohistochemical and molecular genetic markers in women with hyperplastic processes in endometrial tissue.

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Section: Study Results and Discussionmentioning

confidence: 99%

Section: Study Results and Discussionmentioning

confidence: 99%

Section: Study Results and Discussionmentioning

confidence: 99%

Section: Study Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The retrospective analysis results of the endometrial tissue pathological conditions development

Artyomenko

Chumak

Shapoval

2020

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Prognostic Significance of HE4 Tissue Expression in Serous Epithelial Ovarian Carcinoma

Sethi

Kumar

Mathur

et al. 2022

South Asian J Cancer

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Background Human Epididymis protein 4 (HE4) is expressed in ovarian cancer. Preoperative serum testing is still not widely available. This pilot study aimed to investigate the magnitude of expression of HE4 in tissue sections of serous epithelial ovarian carcinoma, its correlation with clinical outcome, and the feasibility of HE4 immunohistochemistry as a prognostic marker. Materials and Method In this ambispective study, immunohistochemistry (IHC) was used to evaluate tissue sections of ovarian serous epithelial carcinoma at primary cytoreductive surgery. On HE4 immunohistochemistry (IHC), the magnitude of HE4 expression was assessed categorically as high or low HE4 expression and semiquantitatively by the H-score, and correlated with clinical outcome in terms of survival status, progression-free survival, and overall survival. Results Of 32 cases, most (n = 31, 96.8%) were positive for HE4 IHC. The mean age was 49 ± 8.2 years; 29 (90.6%) patients were in FIGO stage IIIC; 25 (78.9%) had ≥1cm residual disease after surgery; 31 (96.8%) received adjuvant chemotherapy, either 3-weekly (n = 25, 81.2%) or dose-dense weekly (n = 6, 18.8%) regimen. The majority (n = 31, 96.8%) had a high-grade tumor, of whom 19 (59.4%) had high HE4 expression and 13(40.6%) patients had H-score in the range of 5 to 8. The mean H-score was 6.97 ± 3.61 (range 0 to 12). The overall survival of the study population at 64 months was 36.65% (95% CI: 8.59–66.34), with median overall survival of 59 months. A new scoring system was developed combining categorical HE4 expression and serum CA-125 levels; the combination of HE4 expression with postoperative CA-125 levels was found to be the best prognostic marker for overall survival (p = 0.05). A composite score of 2 identified patients with poor progression-free survival (HR 4.64, p = 0.039) and overall survival (HR 5.45, p = 0.05). Conclusion The new composite scoring system using HE4 IHC with postoperative serum CA-125 levels offers an extremely useful option for prognosticating patients with serous epithelial ovarian carcinoma than serum CA-125 alone. This is useful where preoperative records are not available to the treating clinician.

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Characterisation of Levonorgestrel-Resistant Endometrial Cancer Cells

Dore¹,

Filoche²,

Danielson³

et al. 2021

CMAR

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Background: Endometrial cancer (EC) is the most common gynaecologic malignancy in the developed world, and incidence is increasing in premenopausal women. The levonorgestrel intrauterine system (LNG-IUS) is gaining traction as an alternative treatment for hyperplasia and early-stage EC for women who are unable to undergo surgery. Thirty to 60% of the women do not respond to this treatment, making the unknown mechanisms of levonorgestrel (LNG) resistance a critical obstacle for the conservative management of EC. This study aimed to characterise LNG-IUS treatment resistance in early-stage endometrial cancer in cell-line models. Methods: LNG-resistant endometrial cancer cell lines (MFE296 R and MFE319 R ) and cultures from three early stage endometrial cancer patients were developed. The behavioural profile of MFE296 R and MFE319 R was analysed using proliferation, adhesion, migration (wound healing and transwell) and invasion (spheroid) assays. LNG-sensitive cell lines (MFE296 S and MFE319 S ) were compared to LNG R cell lines (MFE296 R and MFE319 R ). A literature search was conducted to identify possible candidate biomarkers of LNG resistance. RT-qPCR was used to analyse the mRNA expression of 17 candidate biomarkers in MFE296 R and MFE319 R . mRNA expression of the top differentially expressed genes was measured using RT-qPCR in primary cultures. Results: LNG resistance did not affect proliferation or invasion in immortalised endometrial cancer cells. Transwell migration was significantly increased in MFE319 R cells (p=0.03). Cellular adhesion significantly decreased in both MFE296 R cells (p=0.012) and MFE319 R cells (p=0.04). mRNA expression of KLF4 and SATB2 was significantly amplified in MFE296 R and MFE319 R cells. mRNA expression of KLF4 was significantly upregulated LNG-resistant primary cell lines. Conclusion: LNG-resistant cells may have more oncogenic potential than their LNGsensitive counterparts. Significant changes in the mRNA expression of KLF4 and SATB2 of LNG-resistant cells is a promising preliminary result in biomarker discovery for guiding LNG-IUS treatment of early stage endometrial cancer.

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Erratum: HE4 is a novel tissue marker for therapy response and progestin resistance in medium- and low-risk endometrial hyperplasia

Abstract: Background: The aim of the present study was to investigate whether changes in the tissue expression of human epididymisspecific protein 4 (HE4) could predict therapy resistance and relapse after progestin hormone therapy for medium-and low-risk endometrial hyperplasia.

Cited by 5 publications

References 38 publications

The retrospective analysis results of the endometrial tissue pathological conditions development

The retrospective analysis results of the endometrial tissue pathological conditions development

Prognostic Significance of HE4 Tissue Expression in Serous Epithelial Ovarian Carcinoma

Characterisation of Levonorgestrel-Resistant Endometrial Cancer Cells

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