Concomitant p53 and PTEN immunoexpression to predict the risk of malignancy in endometrial polyps

Abrão, Féres; Modotti, Waldir Pereira; Dias, D.S.; Bueloni-Dias, Flávia Neves; Leite, Nilton José; Peres, Gustavo Filipov; Elias, Leonardo Vieira; Domingues, Maria Aparecida Custódio; Dias, Rogério

doi:10.1097/md.0000000000012304

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…In addition to PTEN , approximately 25% of all ECs have been found to harbor mutations in the tumor suppressor TP53 [8]. Although both PTEN and TP53 drive carcinogenesis in many malignancies, the mechanistic role of both genes in endometrial carcinogenesis has not been fully elucidated [9].…”

Section: Introductionmentioning

confidence: 99%

Combined genetic mutations and DNA-methylated genes as biomarkers for endometrial cancer detection from cervical scrapings

Liew

Huang

et al. 2019

Clin Epigenet

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Background: Endometrial cancer is a common gynecologic cancer. Noninvasive molecular biomarkers for triage of high-risk patients for invasive procedures are needed. Based on the success of cytological Pap smear screening, cervical scrapings are a good source of DNA for molecular testing. In addition to genetic lesions, DNA methylation is a promising biomarker. We assessed the usefulness of combining genetic and epigenetic biomarkers from cervical scrapings to detect endometrial carcinomas. Methods: We performed a retrospective case-control study of 96 consecutive cervical scrapings from patients with abnormal uterine bleeding who underwent surgery for diagnostic evaluation. Thirty and 16 cases were diagnosed with type I and type II endometrial cancers, respectively. The remaining non-cancer cases included normal endometrium (n = 12), benign uterine lesions (n = 20), and endometrial hyperplasia (n = 18). Quantitative methylation-specific PCR and mass spectrometry were used for DNA methylation and genetic mutation analysis. Logistic regression was used to evaluate the clinical performance of these candidate biomarkers. Results: We tested the effectiveness of the methylation status of four genes (BHLHE22, CDO1, TBX5, and HAND2) in endometrial cancer detection. The area under the receiver operating characteristic curves ranged from 0.703 to 0.878, and panels of hypermethylated BHLHE22/CDO1/HAND2 (87.0% sensitivity and 86.0% specificity) and BHLHE22/ CDO1/TBX5 (89.1% sensitivity and 80.0% specificity) showed significant differences and could distinguish benign from malignant endometrial lesions. The sensitivity and specificity in endometrial cancer detection for BHLHE22/ CDO1 were 84.8% and 88.0%, respectively. Both type I and II endometrial carcinomas could be detected using a BHLHE22/CDO1-based methylation profile, suggesting that they may have common epigenomes. Moreover, PTEN and TP53 mutations were found in 63.3% of type I and 93.6% of type II endometrial cancers. Unexpectedly, PTEN and TP53 mutations were commonly found in cervical scrapings of the normal endometrium (25% and 33.3%, respectively) and in cases with benign uterine lesions (10% and 50%, respectively). Finally, combinations of any one mutation of PTEN and TP53 mutations had a sensitivity of 91.3%, but a specificity of only 42.0%. Conclusions: Adding PTEN/TP53 mutation testing to BHLHE22/CDO1-based methylation testing did not improve the detection of endometrial cancer.

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Section: Introductionmentioning

confidence: 99%

Combined genetic mutations and DNA-methylated genes as biomarkers for endometrial cancer detection from cervical scrapings

Liew

Huang

et al. 2019

Clin Epigenet

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“…To date, many factors, including clinical and biological, have been studied to predict premalignant or malignant changes of endometrial polyps (7,8). In recent years, immunhistochemical studies conducted to predict the risks of malignancy of endometrial polyps have attracted great attention.…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, immunhistochemical studies conducted to predict the risks of malignancy of endometrial polyps have attracted great attention. Studies on the immune expression of tumor supressor genes, such as p53 and PTEN, have been more common (7,9). P53 was one of the first tumor suppressor genes to be described.…”

Section: Introductionmentioning

confidence: 99%

KISS1, P53, and PTEN immunoexpressions and prediction of malignancy in endometrial intraepithelial neoplasia lesion within endometrial polyp

et al. 2020

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Objective: Aim of this study to evaluate the usefulness of phosphase and tensin homologous deleted on chromosome 10 (PTEN), p53, and kisspeptin (KISS1) immunoexpressions in predicting malignancy in endometrial intraepithelial neoplasia within the endometrial polyps. Material and method: This cross-sectional study was based on chart data from a convenience sample of patients who underwent probe curetage at the Gynecology and Obstetrics Clinic of Başkent University Ankara and Konya Practice and Research Hospitals, Turkey. A total of 169 patients were allocated into 5 groups, comprising the EIN-p group: 62 patients with an endometrial intraepithelial neoplasia lesion within an endometrial polyp, EC group: 17 patients with an endometrial carcinoma, EP-h group: 30 patients with hyperplasia on the background of the polyp but no atypia, EP group: 30 patients with endometrial polyps, and NE group: 30 patients with a normal (proliferative) endometrium. P53, PTEN, and KISS1 expressions between the groups were evaluated. Results: In the EIN-p and EC groups, P53 and KISS1 expressions were moderate or strong. In the NE, EP and EP-h groups, KISS1 was weakly stained and P53 expression was negative. The number of patients with strong p53 and KISS1 expressions in the EC group was higher and this difference was statistically significant (P < 0.001). With PTEN immunostaining, the EC and EIN-P groups were weakly stained, whereas the NE, EP, and EP-h groups had moderate or strong staining. Strong staining rates were higher in patients in the NE and EP groups than in the EP-h group (P < 0.001). Conclusion: In addition to the literature about P53 and PTEN, according to the data obtained herein, it was speculated that KISS1 may play an important role in the malignant transformation of endometrial polyps and it might be used as a predicting marker in this patient group.

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Does obesity modify the expression of cyclin D1 and pten in endometrial polyps in postmenopausal women?

Giordano

Alvarenga

Júnior

et al. 2020

Gynecological Endocrinology

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Concomitant p53 and PTEN immunoexpression to predict the risk of malignancy in endometrial polyps

Cited by 5 publications

References 25 publications

Combined genetic mutations and DNA-methylated genes as biomarkers for endometrial cancer detection from cervical scrapings

Combined genetic mutations and DNA-methylated genes as biomarkers for endometrial cancer detection from cervical scrapings

KISS1, P53, and PTEN immunoexpressions and prediction of malignancy in endometrial intraepithelial neoplasia lesion within endometrial polyp

Does obesity modify the expression of cyclin D1 and pten in endometrial polyps in postmenopausal women?

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