The ARID1A, p53 and ß-Catenin statuses are strong prognosticators in clear cell and endometrioid carcinoma of the ovary and the endometrium

Heckl, Marlene; Schmoeckel, Elisa; Hertlein, Linda; Rottmann, Miriam; Jeschke, Udo; Mayr, Doris

doi:10.1371/journal.pone.0192881

Cited by 44 publications

(40 citation statements)

References 57 publications

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“…In our research group, the same collective of patients has already been worked with. In the corresponding papers, the expression of ARID1A, β-Catenin p16, p21, p53, and the steroid receptors ERα, ERβ, PRα, and PRβ has been described [ 29 , 30 ]. In these studies, tumor material of the exact same patients has been immunohistochemically stained for the above-mentioned proteins and respective expression analyzed.…”

Section: Resultsmentioning

confidence: 99%

MSX1—A Potential Marker for Uterus-Preserving Therapy of Endometrial Carcinomas

Eppich

Kühn

Schmoeckel

et al. 2020

IJMS

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Prognostic factors are of great interest in patients with endometrial cancer. One potential factor could be the protein MSX1, a transcription repressor, that has an inhibitory effect on the cell cycle. For this study, endometrioid endometrial carcinomas (n = 53), clear cell endometrial carcinomas (n = 6), endometrioid ovarian carcinomas (n = 19), and clear cell ovarian carcinomas (n = 11) were immunochemically stained for the protein MSX1 and evaluated using the immunoreactive score (IRS). A significant stronger expression of MSX1 was found in endometrioid endometrial carcinomas (p < 0.001), in grading 2 (moderate differentiation) (p = 0.001), and in tumor material of patients with no involvement of lymph nodes (p = 0.031). Correlations were found between MSX1 expression and the expression of β-Catenin, p21, p53, and the steroid receptors ERα, ERβ, PRα, and PRβ. A significant (p = 0.023) better survival for patients with an MSX1 expression in more than 10% of the tumor cells was observed for endometrioid endometrial carcinomas (21.3 years median survival (MSX1-positive) versus 17.3 years (MSX1-negative)). Although there is evidence that MSX1 expression correlates with improved long-term survival, further studies are necessary to evaluate if MSX1 can be used as a prognostic marker.

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Section: Resultsmentioning

confidence: 99%

MSX1—A Potential Marker for Uterus-Preserving Therapy of Endometrial Carcinomas

Eppich

Kühn

Schmoeckel

et al. 2020

IJMS

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“…Heckel et al found that the expression of ARID1A and absent nuclear β-Catenin staining were positive prognosticators in endometrioid and clear-cell carcinoma of the uterus and the ovaries (Heckl et al 2018 ). We detected a positive correlation of SIRT1 expression in the examined entities with both proteins, ARID1A and β-Catenin.…”

Section: Discussionmentioning

confidence: 99%

Sirtuin1 expression and survival in endometrial and clear-cell uterine cancer

Beyer

Chen

Meister

et al. 2020

Histochem Cell Biol

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Several risk factors like obesity and hyperlipidemia were described for endometrial cancer. Here, the nuclear NAD-dependent histone-deacetylase Sirtuin1 (SIRT1) seems to be important. SIRT1 is also involved in cell regulatory mechanisms and can serve as tumor promotor or suppressor. Its role in tumor biology is not clear yet. In this study, we evaluated and correlated the SIRT1 expression with patients' tumor characteristics in endometrioid and clear-cell cancer of the uterus. 65 paraffinembedded samples of patients with endometrial and clear-cell cancer of the uterus were immunohistochemically stained and SIRT1 expression was evaluated by immunoreactive score. The results were correlated to clinical and pathological tumor characteristics as well as to the expression of ARID1A and β-Catenin. The staining was significantly more intensive in uterine endometrioid carcinoma compared to uterine clear-cell carcinoma (p = 0.007). The expression of SIRT1 correlated significantly with the membranous expression of β-Catenin (p = 0.028) and ARID1A (p = 0.021). Patients with positive Sir-tuin1 expression had a significantly better progression-free survival (p = 0.042), the overall survival showed a trend towards a better prognosis (p = 0.070). SIRT1 expression seems to be associated with improved progression-free survival in uterine cancer (endometrioid and clear-cell) and is correlated to the tumor suppressors β-Catenin and ARID1A. Further studies are necessary to elucidate the role of SIRT1 in uterine and ovarian cancer and its potential as a therapeutic target.

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“…The membrane was blocked at room temperature in a solution of 3% nonfat dry milk in PBS and 0.1% Tween-20 and then rinsed in PBS/0.1% Tween-20. Blots were incubated with diluted solutions of anti-P53 (1:1000, Cell Signaling Tech, Danvers, MA, USA) [ 15 ] and anti-HNF-1β (1:500, GeneTex) [ 16 , 17 ] antibodies (previously reported expression in CCC) and treated with 1:5000 diluted anti-rabbit immunoglobulin G horseradish peroxidase (HRP) for staining (Amersham GE, Taipei, Taiwan). GAPDH proteins (1: 200, GeneTex) were used as internal controls.…”

Section: Methodsmentioning

confidence: 99%

A clear cancer cell line (150057) derived from human endometrial carcinoma harbors two novel mutations

Chang

Ding

2020

BMC Cancer

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Background Cell lines are extremely useful for both basic and clinical research. Thus, establishing endometrial cancer cell lines with malignant histology is important. This study aimed to extensively characterize an endometrial clear cell carcinoma cell line. Methods This cell line, named 150,057, was derived from the endometrial clear cell cancer of a 63-year-old woman. The morphology, chromosomes, chemosensitivity, tumor markers, xenotransplantation characteristics, and cancer-related genes of the cell line were characterized. Results This cell line exhibited adequate growth, being passaged more than 70 times. The morphology of the cells was polygonal with a cobblestone-like appearance. Karyotyping of the cell line revealed a hypodiploid chromosomal number. 150057 cells expressed CA19–9 and CA125. The cell line was sensitive to doxorubicin, paclitaxel, carboplatin, and cisplatin. After the cells were transplanted into the subcutaneous region of non-obese diabetic-severe combined immunodeficiency mice, they generated xenograft tumors with similar histology as the original tumor. A total of 59 somatic nucleotide mutations were identified in 25 of the 53 examined tumor suppressor genes and oncogenes. Two novel mutations were found in FGFR3 and ARID1A. Conclusion We established and characterized an endometrial clear cell carcinoma cell line that may be useful in carcinogenesis and treatment research for endometrial cancer.

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The ARID1A, p53 and ß-Catenin statuses are strong prognosticators in clear cell and endometrioid carcinoma of the ovary and the endometrium

Cited by 44 publications

References 57 publications

MSX1—A Potential Marker for Uterus-Preserving Therapy of Endometrial Carcinomas

MSX1—A Potential Marker for Uterus-Preserving Therapy of Endometrial Carcinomas

Sirtuin1 expression and survival in endometrial and clear-cell uterine cancer

A clear cancer cell line (150057) derived from human endometrial carcinoma harbors two novel mutations

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