CpG-island Methylation of the ER Promoter in Colorectal Cancer: Analysis of Micrometastases in Lymph Nodes from UICC Stage I and II Patients

Overview

Journal Br J Cancer

Specialty Oncology

Date 2009 Jan 15

PMID 19142184

Citations 13

Authors

J Harder

V Engelstaedter

H Usadel

S Lassmann

M Werner

P Baier

F Otto

M Varbanova

E Schaeffner

M Olschewski

H E Blum

O G Opitz

Affiliations

Soon will be listed here.

Abstract

Patients with UICC stage II colorectal cancer (CRC) have a risk of approximately 20% to develop disease recurrence after tumour resection. The presence and significance of micrometastases for locoregional recurrence in these patients lacking histopathological lymph node involvement on routine stained HE sections is undefined. Oestrogen receptor (ER) promoter methylation has earlier been identified in CRC. Therefore, we evaluated the methylation status of the ER promoter in lymph nodes from 49 patients with CRC UICC stage I and II as a molecular marker of micrometastases and predictor of local recurrence. DNA from 574 paraffin-embedded lymph nodes was isolated and treated with bisulphite. For the detection of methylated ER promoter sequences, quantitative real-time methylation-specific PCR was used. Of the 49 patients tested, 15 (31%) had ER methylation-positive lymph nodes. Thirteen of those (86%) remained disease free and two (14%) developed local recurrence. In the resected lymph nodes of 34 of the 49 patients (69%), no ER promoter methylation could be detected and none of these patients experienced a local relapse. The methylation status of the ER promoter in lymph nodes of UICC stage I and II CRC patients may be a useful marker for the identification of patients at a high risk for local recurrence.

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References

Lee M, Hong C, Yoon S, Lim S, Park K, Lee M . Isolated tumor cells in lymph nodes are not a prognostic marker for patients with stage I and stage II colorectal cancer. J Surg Oncol. 2005; 93(1):13-8. DOI: 10.1002/jso.20294. View

Issa J, Ottaviano Y, Celano P, Hamilton S, Davidson N, Baylin S . Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet. 1994; 7(4):536-40. DOI: 10.1038/ng0894-536. View

Rosenberg R, Hoos A, Mueller J, Baier P, Stricker D, Werner M . Prognostic significance of cytokeratin-20 reverse transcriptase polymerase chain reaction in lymph nodes of node-negative colorectal cancer patients. J Clin Oncol. 2002; 20(4):1049-55. DOI: 10.1200/JCO.2002.20.4.1049. View

Waldman S, Barber M, PEARLMAN J, Park J, George R, Parkinson S . Heterogeneity of guanylyl cyclase C expressed by human colorectal cancer cell lines in vitro. Cancer Epidemiol Biomarkers Prev. 1998; 7(6):505-14. View

Messerini L, Cianchi F, Cortesini C, Comin C . Incidence and prognostic significance of occult tumor cells in lymph nodes from patients with stage IIA colorectal carcinoma. Hum Pathol. 2006; 37(10):1259-67. DOI: 10.1016/j.humpath.2006.04.023. View

Yagci G, Unlu A, Kurt B, Can M, Kaymakcioglu N, Cetiner S . Detection of micrometastases and skip metastases with ex vivo sentinel node mapping in carcinoma of the colon and rectum. Int J Colorectal Dis. 2006; 22(2):167-73. DOI: 10.1007/s00384-006-0132-7. View

Bernini A, Spencer M, Frizelle S, Madoff R, Willmott L, McCormick S . Evidence for colorectal cancer micrometastases using reverse transcriptase-polymerase chain reaction analysis of MUC2 in lymph nodes. Cancer Detect Prev. 2000; 24(1):72-9. View

Landis S, Murray T, Bolden S, Wingo P . Cancer statistics, 1998. CA Cancer J Clin. 1998; 48(1):6-29. DOI: 10.3322/canjclin.48.1.6. View

Issa J, Zehnbauer B, Civin C, Collector M, Sharkis S, Davidson N . The estrogen receptor CpG island is methylated in most hematopoietic neoplasms. Cancer Res. 1996; 56(5):973-77. View

10.

Miyake Y, Yamamoto H, Fujiwara Y, Ohue M, Sugita Y, Tomita N . Extensive micrometastases to lymph nodes as a marker for rapid recurrence of colorectal cancer: a study of lymphatic mapping. Clin Cancer Res. 2001; 7(5):1350-7. View

11.

Bostick P, Chatterjee S, Chi D, Huynh K, Giuliano A, Cote R . Limitations of specific reverse-transcriptase polymerase chain reaction markers in the detection of metastases in the lymph nodes and blood of breast cancer patients. J Clin Oncol. 1998; 16(8):2632-40. DOI: 10.1200/JCO.1998.16.8.2632. View

12.

Esteller M, Corn P, Baylin S, Herman J . A gene hypermethylation profile of human cancer. Cancer Res. 2001; 61(8):3225-9. View

13.

Jung R, Petersen K, Kruger W, Wolf M, Wagener C, Zander A . Detection of micrometastasis by cytokeratin 20 RT-PCR is limited due to stable background transcription in granulocytes. Br J Cancer. 1999; 81(5):870-3. PMC: 2374287. DOI: 10.1038/sj.bjc.6690778. View

14.

Futamura M, Takagi Y, Koumura H, Kida H, Tanemura H, Shimokawa K . Spread of colorectal cancer micrometastases in regional lymph nodes by reverse transcriptase-polymerase chain reactions for carcinoembryonic antigen and cytokeratin 20. J Surg Oncol. 1998; 68(1):34-40. DOI: 10.1002/(sici)1096-9098(199805)68:1<34::aid-jso8>3.0.co;2-m. View

15.

Eads C, Lord R, Kurumboor S, Wickramasinghe K, Skinner M, Long T . Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma. Cancer Res. 2000; 60(18):5021-6. View

16.

Lassmann S, Bauer M, Rosenberg R, Nekarda H, Soong R, Ruger R . Identification of occult tumor cells in node negative lymph nodes of colorectal cancer patients by cytokeratin 20 gene and protein expression. Int J Colorectal Dis. 2003; 19(2):87-94. DOI: 10.1007/s00384-003-0530-z. View

17.

de Maat M, van de Velde C, van der Werff M, Putter H, Umetani N, Meershoek Klein-Kranenbarg E . Quantitative analysis of methylation of genomic loci in early-stage rectal cancer predicts distant recurrence. J Clin Oncol. 2008; 26(14):2327-35. DOI: 10.1200/JCO.2007.14.0723. View

18.

Jass J . Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 2007; 50(1):113-30. DOI: 10.1111/j.1365-2559.2006.02549.x. View

19.

Kim G, Colangelo L, Wieand H, Paik S, Kirsch I, Wolmark N . Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J Clin Oncol. 2007; 25(7):767-72. DOI: 10.1200/JCO.2006.05.8172. View

20.

Pellise M, Castells A, Gines A, Agrelo R, Sole M, Castellvi-Bel S . Detection of lymph node micrometastases by gene promoter hypermethylation in samples obtained by endosonography- guided fine-needle aspiration biopsy. Clin Cancer Res. 2004; 10(13):4444-9. DOI: 10.1158/1078-0432.CCR-03-0600. View