Promoter hypermethylation of tumor‐related genes in peritoneal lavage and the prognosis of patients with colorectal cancer

Kamiyama, Hidenori; Noda, Hiroshi; Takata, Osamu; Suzuki, Koichi; Kawamura, Yutaka; Konishi, Fumio

doi:10.1002/jso.21291

Cited by 23 publications

(15 citation statements)

References 31 publications

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“…The relation of p16 methylation with clin-114 icopathological variables, in these patients, has yield discrepancies in the literature. Although methylation could not be associated to clinicopathological variables by some authors (28,38), it has been associated to the following: Dukes stage and lymphatic invasion (35); also to age, sex, tumor location, differentiation grade and histological type (36). In this study, the p16 gene promoter methylation was found to be associated with both, poor differentiation grade and proximal tumor location.…”

Section: Discussioncontrasting

confidence: 61%

“…None of the previously published studies of p16 showed high population size, with so extended follow-up in homogeneous population, only with sporadic cases with no previous treatment (24)(25)(26)(27)(28)(29). The only cases who reported higher population size with survival analyses in long follow-up whether had lower median follow up (23) whether consisted of multicenter studies, introducing variability through diverse laboratory analyses and different clinical management, including family history cases (25).…”

Section: Discussionmentioning

confidence: 99%

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p16 gene methylation in colorectal cancer patients with long-term follow-up

Veganzones¹,

Rafael-Fernandez²,

Vidaurreta-Lázaro³

et al. 2012

Rev. esp. enferm. dig.

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Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

p16 gene methylation in colorectal cancer patients with long-term follow-up

Veganzones¹,

Rafael-Fernandez²,

Vidaurreta-Lázaro³

et al. 2012

Rev. esp. enferm. dig.

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“…A previous study reported that the frequencies of aberrant promoter methylation were 16% for cadherin 1, 2% for p16, 4% for MGMT and 24% for APC (47). An aberrant methylation of ≥1 of these genes was identified in 45 of 51 (88%) primary tumors (48). In the present cohort, APC was methylated in 33% of patients with early oCRC and in 53.7% of patients with mCRC.…”

Section: Discussionsupporting

confidence: 53%

“…Hypermethylation of the APC promoter has been reported in early steps of carcinogenesis in several tumors (46). A previous study reported that the frequencies of aberrant promoter methylation were 16% for cadherin 1, 2% for p16, 4% for MGMT and 24% for APC (47). An aberrant methylation of ≥1 of these genes was identified in 45 of 51 (88%) primary tumors (48).…”

Section: Discussionmentioning

confidence: 92%

Methylation status of the APC and RASSF1A promoter in cell-free circulating DNA and its prognostic role in patients with colorectal cancer

et al. 2016

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Abstract. DNA methylation is the most frequent epigenetic alteration. Using methylation-specific polymerase chain reaction (MSP), the methylation status of the adenomatous polyposis coli (APC) and Ras association domain family 1 isoform A (RASSF1A) genes was examined in cell-free circulating DNA from 155 plasma samples obtained from patients with early and advanced colorectal cancer (CRC). APC and RASSF1A hypermethylation was frequently observed in both early and advanced disease, and was significantly associated with a poorer disease outcome. The methylation status of the APC and RASSF1A promoters was investigated in cell-free DNA of patients with CRC. Using MSP, the promoter methylation status of APC and RASSF1A was examined in 155 blood samples obtained from patients with CRC, 88 of whom had operable CRC (oCRC) and 67 had metastatic CRC (mCRC). The frequency of APC methylation in patients with oCRC was 33%. Methylated APC promoter was significantly associated with older age (P= 0.012), higher stage (P= 0.014) and methylated RASSF1A status (P= 0.050). The frequency of APC methylation in patients with mCRC was 53.7%. In these patients, APC methylation was significantly associated with methylated RASSF1A status (P=0.016). The frequency of RASSF1A methylation in patients with oCRC was 25%. Methylated RASSF1A in oCRC was significantly associated with higher stage (P=0.021). The frequency of RASSF1A methylation in mCRC was 44.8%. Methylated RASSF1A in mCRC was associated with moderate differentiation (P=0.012), high levels of carcinoembryonic antigen (P=0.023) and methylated APC status (P=0.016). Patients with an unmethylated APC gene had better survival in both early (81±5 vs. 27±4 months, P<0.001) and advanced disease (37±7 vs. 15±3 months, P<0.001), compared with patients with methylated APC. Patients with an unmethylated RASSF1A gene had better survival in both early (71±6 vs. 46±8 months, P<0.001) and advanced disease (28±4 vs. 16±3 months, P<0.001) than patients with methylated RASSF1A. The observed significant correlations between APC and RASSF1A promoter methylation status and survival may be indicative of a prognostic role for these genes in CRC, which requires additional testing in larger studies.

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“…37,40,[43][44][45][46][47][48][49] The methylation of p16, as evaluated in DNA extracted from primary tumors, peritoneal lavage fluid, and serum from patients with colorectal cancer, has been related to more advanced tumor stage and to significantly poorer overall and disease-free survival rates. 37,45,50,51 It is noteworthy that protein expression of p16 is correlated inversely with the degree of methylation, supporting the argument that immunohistochemistry for the protein could be used as a surrogate marker for p16 epigenetic silencing. 47 Furthermore, the use of p16 protein expression has been suggested as a screening tool for the selection of patients who undergo genetic testing for Lynch syndrome.…”

Section: Original Article 4480mentioning

confidence: 55%

Expression of p16 in lymph node metastases of adjuvantly treated stage III colorectal cancer patients identifies poor prognostic subgroups

Karamitopoulou

Zlobec

Koumarianou

et al. 2010

Cancer

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BACKGROUND:The objective of identifying protein biomarkers for patients with stage III and IV colorectal cancer is to improve risk stratification and, thus, to identify patients in the postoperative setting who may benefit from more targeted treatment. The objective of the current study was to determine the prognostic value of 19 protein markers assessed in primary tumors and matched lymph node (LN) metastases from patients with stage III and IV colorectal cancer. METHODS: Matched primary tumors and LN metastases from 82 patients with stage III and IV colorectal cancer were mounted onto a multiple-punch tissue microarray and were stained for 19 protein markers involved in tumor progression (b-catenin, E-cadherin, epidermal growth factor receptor, phosphorylated extracellular signal-regulated kinase [pERK], receptor for hyaluronic acid-mediated motility, phosphorylated protein kinase B, p21, p16, B-cell lymphoma 2, Ki67, apoptotic protease activating factor 1, mammalian sterile 20-like kinase 1, Raf kinase inhibitor protein, vascular endothelial growth factor, ephrin type-B receptor 2, matrix metalloproteinase 7, laminin5c2, mucin 1 [MUC1], and caudal-related homeobox 2). The prognostic effects of biomarkers in both primary tumor and positive LNs were assessed. RESULTS: MUC1, pERK and p16 in LN (P ¼ .002, P ¼ .014, and P ¼ .002, respectively) had independent prognostic value. In patients with stage III disease who received adjuvant treatment, negative p16 expression was associated with highly unfavorable outcomes overall (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.1-0.6; P ¼ .005) when the analysis was stratified by pathologic tumor classification (HR, 0.25; 95% CI, 0.1-0.7; P ¼ .005), age (HR, 0.23; 95% CI, 0.1-0.6; P ¼ .004), and LN ratio (HR, 0.26; 95% CI, 0.1-0.7; P ¼ .007); and, in multivariate analysis, it was associated with performance status and the receipt of folic acid treatment (HR, 0.29; 95% CI, 0.09-0.89; P ¼ .03). CONCLUSIONS: The loss of p16 in LN metastases contributed to adverse outcomes in adjuvantly treated patients with stage III colorectal cancer independent of pathologic tumor classification, age, LN ratio, performance status, or folic acid treatment. The current results support the investigation of p16 as a prognostic and potential predictive biomarker for future randomized trials of patients with stage III colorectal cancer. Cancer 2010;116:4474-86.

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Promoter hypermethylation of tumor‐related genes in peritoneal lavage and the prognosis of patients with colorectal cancer

Abstract: These findings suggest that disseminated tumor cells in PLF detected by QMSP may correlate with the postoperative clinical course of patients undergoing curative surgery for CRC.

Cited by 23 publications

References 31 publications

p16 gene methylation in colorectal cancer patients with long-term follow-up

p16 gene methylation in colorectal cancer patients with long-term follow-up

Methylation status of the APC and RASSF1A promoter in cell-free circulating DNA and its prognostic role in patients with colorectal cancer

Expression of p16 in lymph node metastases of adjuvantly treated stage III colorectal cancer patients identifies poor prognostic subgroups

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