Dataset Information

Impact of RASSF1A gene methylation on the metastatic axillary nodal status in breast cancer patients.

ABSTRACT: Hypermethylation of CpG islands is a hallmark of cancer and occurs at an early stage in breast tumorigenesis. To gain insight into the epigenetic switches that may promote and/or contribute to the initial neoplastic events during breast carcinogenesis, the present study focused on the DNA methylation profile of invasive breast carcinoma. The aim of the study was to evaluate the prognostic significance of Ras association domain family 1 isoform A (RASSF1A) promoter methylation status in operable breast cancer, and to analyze the utility of this biomarker regarding its association with metastatic and nonmetastatic axillary nodal status. For this purpose, formalin-fixed, paraffin-embedded tissue specimens from 116 breast cancer patients with known axillary nodal status were subjected to assessment of RASSF1A promoter methylation status by methylation-specific polymerase chain reaction (MSP) and methylation-sensitive high-resolution melting assay, and the results were subsequently validated by bisulfite sequencing. A multinomial logistic regression model was used to model the dependence of distinct levels of methylation status of the RASSF1A promoter on the nodal status. Promoter region CpG hypermethylation was identified by MSP in 97 (83.6%) of 116 primary breast tumors, while hypermethylation of RASSF1A was confirmed by MS-HRM in 107 (92.2%) of 116 cases of breast cancer. Based on the results of the multinomial logistic regression model, there was no significant difference between the frequency of RASSF1A promoter methylation and axillary lymph node status of patients in general. However, upon adjustment of pN stage, an association was identified between pN0 lymph node-negative status (without axillary metastases) and percentage of RASSF1A methylation in two groups of heterogeneous methylated alleles with ?50% methylated (P<0.05) and >50% methylated alleles (P<0.0001). If a patients' nodal status changes from pN- to pN+ then the risk of having >50% methylated alleles increases by 7%. The present study revealed a specific phenomenon, suggesting that the presence of heterogeneous methylated alleles in the RASSF1A gene is significantly associated with lymph node-negative status in breast cancer patients. Furthermore, greater significance with negative axillary nodal status was observed with a higher level of heterogeneous methylated alleles in the RASSF1A gene.

SUBMITTER: Jezkova E

PROVIDER: S-EPMC5494671 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Impact of <i>RASSF1A</i> gene methylation on the metastatic axillary nodal status in breast cancer patients.

Jezkova Eva E Zubor Pavol P Kajo Karol K Grendar Marian M Dokus Karol K Adamkov Marian M Lasabova Zora Z Plank Lukas L Danko Jan J

Oncology letters 20170518 1

Hypermethylation of CpG islands is a hallmark of cancer and occurs at an early stage in breast tumorigenesis. To gain insight into the epigenetic switches that may promote and/or contribute to the initial neoplastic events during breast carcinogenesis, the present study focused on the DNA methylation profile of invasive breast carcinoma. The aim of the study was to evaluate the prognostic significance of Ras association domain family 1 isoform A (<i>RASSF1A</i>) promoter methylation status in op ...[more]

PMID: 28693231

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Project description:ObjectiveTo investigate the potential association among preoperative breast MRI features, axillary nodal burden (ANB), and disease-free survival (DFS) in patients with early-stage breast cancer.Materials and methodsWe retrospectively reviewed 297 patients with early-stage breast cancer (cT1-2N0M0) who underwent preoperative MRI between December 2016 and December 2018. Based on the number of positive axillary lymph nodes (LNs) determined by postoperative pathology, the patients were divided into high nodal burden (HNB; ≥3 positive LNs) and non-HNB (<3 positive LNs) groups. Univariable and multivariable logistic regression analyses were performed to identify independent risk factors associated with ANB. Predictive efficacy was evaluated using the receiver operating characteristic (ROC) curve and area under the curve (AUC). Univariable and multivariable Cox proportional hazards regression analyses were performed to determine preoperative features associated with DFS.ResultsWe included 47 and 250 patients in the HNB and non-HNB groups, respectively. Multivariable logistic regression analysis revealed that multifocality/multicentricity (adjusted odds ratio [OR] = 3.905, 95% confidence interval [CI]: 1.685-9.051, P = 0.001) and peritumoral edema (adjusted OR = 3.734, 95% CI: 1.644-8.479, P = 0.002) were independent risk factors for HNB. Combined peritumoral edema and multifocality/multicentricity achieved an AUC of 0.760 (95% CI: 0.707-0.807) for predicting HNB, with a sensitivity and specificity of 83.0% and 63.2%, respectively. During the median follow-up period of 45 months (range, 5-61 months), 26 cases (8.75%) of breast cancer recurrence were observed. Multivariable Cox proportional hazards regression analysis indicated that younger age (adjusted hazard ratio [HR] = 3.166, 95% CI: 1.200-8.352, P = 0.021), larger tumor size (adjusted HR = 4.370, 95% CI: 1.671-11.428, P = 0.002), and multifocality/multicentricity (adjusted HR = 5.059, 95% CI: 2.166-11.818, P < 0.001) were independently associated with DFS.ConclusionPreoperative breast MRI features may be associated with ANB and DFS in patients with early-stage breast cancer.

Dataset Information

Impact of RASSF1A gene methylation on the metastatic axillary nodal status in breast cancer patients.

Publications

Impact of <i>RASSF1A</i> gene methylation on the metastatic axillary nodal status in breast cancer patients.

Similar Datasets

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