scholarly journals Assessment of Aberrant Promoter Hypermethylation of RASSF1a and P16 in Endometrial Carcinoma

2021 ◽  
Vol 8 (7) ◽  
pp. 402-409
Author(s):  
Nagaratna Shivanandappa ◽  
Shalini N Swamy ◽  
Sandeep Kumar S

Endometrial carcinoma is one of the most common gynecological malignancies known to affect around 142000 women worldwide. Aberrant promoter hypermethylation of tumor suppressor genes is a common epigenetic alteration reported in cancers. In the present study we report the aberrant promoter hypermethylation of RASSF1a and p16 in 78 endometrial cancer patients. Methods: Endometrial carcinoma samples were collected after pathological examination and DNA was extracted. The DNA was subjected to sodium bisulfite modification and then used to perform methylation specific PCR. The PCR was performed using a two step procedure of nested and methylation specific PCR. The PCR product was visualized using agarose gel electrophoresis. The results obtained were correlated with various clinicopathological parameters. Chi square test was used for statistical analysis and a p-value of <0.05 was considered statistically significant. Result: 60 of the 78 (76.92%) samples showed methylation for RASSF1a gene. 28 of the 78 (35.8%) samples showed methylation for p16 gene. A higher methylation frequency was observed for RASSF1a in the endometrioid and poorly differentiated histological subtypes and stage I and II of the disease. Conclusion: Aberrant promoter hypermethylation of RASSF1a and p16 is known to play an important role in endometrial cancer initiation and progression. The methylation patterns can be used as an important molecular marker for early diagnosis and prognosis of endometrial cancer. Keywords: Epigenetic alterations, DNA Hypermethylation, Endometrial cancer, RASSF1a, p16, Methylation-specific PCR.

2021 ◽  
Vol 9 (3) ◽  
pp. 160-166
Author(s):  
Nagaratna Shivanandappa ◽  
◽  
Dr. Shalini N Swamy ◽  
Dr. Sandeep Kumar S ◽  
Dr. Suma Sheshadri ◽  
...  

Endometrial cancer is the seventh most common cancer in women worldwide with an age-standardized rate of 8.4 per 100,000 women. Epigenetic alterations such as promoterhypermethylation of TSGs are known to be early events in carcinogenesis. The aim of the presentstudy, we assessed the aberrant promoter hypermethylation pattern of RAR-β in 78 endometrialcancer samples. Methods: DNA was isolated from endometrial carcinoma samples and normaltissues and aberrant promoter hypermethylation was assessed using nested and methylation-specificPCR. The Chi-square test was used for statistical analysis and a p-value<0.05 was considered to bestatistically significant. Results: 40 of the 78 (51.28%) endometrial carcinoma samples showedaberrant hypermethylation of the RAR-β gene. Methylation status in each histological subtype, gradeand stage of the disease was also assessed. Conclusion: Aberrant hypermethylation is an importantearly epigenetic alteration that occurs during tumorigenesis. The Data shown here reports thatpromoter hypermethylation of RAR-β occurs in endometrial carcinoma and therefore could be usedas a potential marker for early diagnosis and prognosis of the disease.


2020 ◽  
Vol 17 (36) ◽  
pp. 1075-1082
Author(s):  
Mohammed FAWZI ◽  
Ahmed TAIFI ◽  
Zahraa Kamil Kadhim LAWI

Colorectal cancer (CRC) is one of the most common diagnosis malignancies with different risk factors, including environmental and genetic. Several genes, called tumor suppressor genes, play an essential role in inhibiting these risk factors by preventing tumor development. One of these genes is somatostatin (SST). Somatostatin is an antiproliferative peptide with pro-apoptotic effects that enhance cell death to prevent tumor growth. This study aimed to investigate the association relationship between DNA methylation in SST promotor and colorectal cancer progression. After DNA bisulfite conversion, SST promoter methylation was examined using quantitative methylation‐specific PCR (qMSP) in 71 cases (19 metastasis CRC, 28 early-stage CRC, and 24 healthy controls). Quantitative methylation‐specific PCR (qMSP) is a real-time PCR method used to determine the unmethylated and methylated cytosine residues using a specific set of primers. The percentage of hypermethylation in SST promoter was 17%, 60%, and 79% for healthy controls, early-stage, and metastasis CRC groups. The results showed a significant association between DNA hypermethylation of SST promoter and CRC progression. P-values were 0.0364 for the early-stage group and 0.0138 for the metastasis group. The results also supported that the DNA hypermethylation block the expression of SST, which in turn induce carcinogenesis. The detection of SST promoter hypermethylation at early stage of cancer could be used as a biomarker for screening and prognosis of CRC.


2021 ◽  
Vol 9 (4) ◽  
pp. 241-248
Author(s):  
Nagaratna Shivanandappa ◽  
◽  
Dr. Shalini N Swamy ◽  
Dr. Sandeep Kumar S ◽  
Dr. Suma Sheshadri ◽  
...  

Introduction: Endometrial cancer is one of the most common cancers in women worldwide. Theunderlying cause of endometrial tumorigenesis remains elusive. Several genetic and epigeneticalterations are known to be involved in the carcinogenesis of endometrial carcinoma. One importantand early epigenetic alteration that is attributed to endometrial carcinoma is the aberrant promoterhypermethylation of gene promoters. In this study, we have assessed the aberrant promoterhypermethylation of APC and BRCA1 in 78 endometrial cancer samples. Methods: Histologicallyconfirmed tumour tissue samples were obtained post-surgery and DNA was extracted. The DNA wassubjected to sodium bisulfite conversion and used as a template for a polymerase chain reaction.The PCR was performed using a nested PCR followed by methylation specific PCR. Results: A33.33% and 46.15% methylation frequency was observed for APC and BRCA1 genes respectively. Ahigher percentage of methylation was observed in stage IV for APC (66.66%) and in stage II forBRCA1 (88.88%). Conclusion: Aberrant promoter hypermethylation is an early event inendometrial carcinoma and can serve as a useful molecular marker for diagnosis and prognosis ofthe disease along with existing screening modalities.


2014 ◽  
Vol 67 (12) ◽  
pp. 1067-1071 ◽  
Author(s):  
Lise M A De Strooper ◽  
Marjolein van Zummeren ◽  
Renske D M Steenbergen ◽  
Maaike C G Bleeker ◽  
Albertus T Hesselink ◽  
...  

AimsGene promoter hypermethylation is recognised as an essential early step in carcinogenesis, indicating important application areas for DNA methylation analysis in early cancer detection. The current study was set out to assess the performance of CADM1, MAL and miR124-2 methylation analysis in cervical scrapes for detection of cervical and endometrial cancer.MethodsA series of cervical scrapes of women with cervical (n=79) or endometrial (n=21) cancer, cervical intraepithelial neoplasia grade 3 (CIN3) (n=16) or CIN2 (n=32), and women without evidence of CIN2 or worse (n=120) were assessed for methylation of CADM1, MAL and miR124-2. Methylation analysis was done by the PreCursor-M assay, a multiplex quantitative methylation-specific PCR.ResultsAll samples of women with cervical cancer (79/79, 100%), independent of the histotype, and 76% (16/21; 95% CI 58.0% to 94.4%) of women with endometrial cancer scored positive for DNA methylation for at least one of the three genes. In women without cancer, methylation frequencies increased significantly with severity of disease from 19.2% (23/120; 95% CI 12.1% to 26.2%) in women without CIN2 or worse to 37.5% (12/32; 95% CI 20.7% to 54.3%) and 68.8% (11/16; 95% CI 46.0% to 91.5%) in women with CIN2 and CIN3, respectively. Overall methylation positivity and the number of methylated genes increased proportionally to the lesion severity.ConclusionsDNA methylation analysis of CADM1, MAL and miR124-2 in cervical scrapes consistently detects cervical cancer and the majority of CIN3 lesions, and has the capacity to broaden its use on cervical scrapes through the detection of a substantial subset of endometrial carcinomas.


2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096170
Author(s):  
Tianyu Zhang ◽  
Xiao Li ◽  
Ganwei Liu ◽  
Xiuyuan Chen ◽  
Yanguo Liu

A diaphragmatic tumor is usually caused by metastasis from lung cancer, malignant mesothelioma, and malignant thymoma. Endometrial cancer is rarely involved in metastasis to the diaphragm. A right anterior mediastinal tumor was found in a 60-year-old woman who was initially diagnosed with endometrial carcinoma. There was initially no relationship between the right anterior mediastinal tumor and endometrial carcinoma. Radical curative surgery was performed for endometrial carcinoma. The endometrial carcinoma stage was IA. The patient was admitted to the Department of Thoracic Surgery 6 months after the curative surgery. Intraoperative exploration showed a tumor growing in the right diaphragm. Right diaphragmotomy was performed. Immunohistochemistry showed metastasis of endometrial carcinoma to the diaphragm. Endometrial cancer solitary metastasis to the diaphragm is rare. Clinicians should be aware of this possibility. Surgical treatment followed by a pathological examination is the most useful method for determining the diagnosis of a diaphragmatic tumor due to metastasis of endometrial cancer.


2020 ◽  
Vol 8 (A) ◽  
pp. 306-310
Author(s):  
Nour El Hoda S. Ismael ◽  
Hala M. Naguib ◽  
Suzan Mohamed Talaat ◽  
Rasha F. Bakry

BACKGROUND: Endometrial cancer (EC) is the fourth most common female cancer worldwide constituting 7% of cancer in women. It is a disease of older, postmenopausal women. The most of these patients have an identifiable source of excess estrogen, while in a small subset the pathogenesis is related to mismatch repair abnormality and lynch syndrome (LC). Mismatch repair behave as tumor suppressors and the most clinically relevant include MLH1, MSH2, MSH6, and PMS2. mutations in mismatch repair (MMR) results in a strong mutator phenotype known as microsatellite instability, which is a hallmark of LC-associated cancers. AIM: The aim of the study was to study microsatellite instability in endometrial cancer using the immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). MATERIAL AND METHODS: Sixty EC cases were studied using MLH-1, MSH-2, MSH-6, and PMS-2 immunohistochemistry and their expression was correlated with different clinicopathologic parameters. RESULTS: A statistically significant relationship exists between MMR immunohistochemistry (IHC) proteins and tumor grade. Intact MMR proteins profile was associated with the lower tumor grade (31.3% were Grade 1 and 46.9% were Grade 2). Combined loss of MLH1/PMS2, combined loss of MSH2/MSH6, and isolated loss of PMS2 were also associated with the lower tumor grade while isolated loss of MSH6 was associated with the high tumor grade. However, no statistically significant correlation was found between MMR IHC proteins expression and the age of patients; tumor histopathological types, or FIGO stage. CONCLUSION: A statistically significant correlation between the tumor grade of EC cases and the MMR IHC proteins was found. Further studies are recommended to assess correlation between MMR proteins defect and different clinicopathological parameters of endometrial carcinoma.


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