Prognostic relevance of occult metastases detected by cytokeratin 20 and mucin 2 mRNA levels in sentinel lymph nodes from colon cancer patients

Ann Surg Oncol. 2012 Nov;19(12):3719-26. doi: 10.1245/s10434-012-2454-8. Epub 2012 Jul 3.

Abstract

Purpose: To investigate the prognostic value of occult metastases detected by quantitative measurements of candidate biomarkers in sentinel lymph nodes (SLNs) from patients curatively resected for colon cancer.

Methods: Resection specimens from consecutive patients undergoing surgery for localized colon cancer were subjected to ex vivo SLN mapping. SLNs were examined for the presence of metastases by routine hematoxylin-erythrosin-safranin staining and by cytokeratin 20 (CK20) and mucin 2 (MUC2) mRNA quantification. The patients were stratified according to KRAS and BRAF mutation status and microsatellite instability status in their primary tumors. Survival end points were analyzed by Kaplan-Meier survival estimates and log-rank tests.

Results: A total of 817 SLNs were identified in 206 (97 %) of the 213 included patients. Routine histological examination of SLNs and other regional lymph nodes identified 63 patients with positive nodes (pN+), of which 42 (67 %) were positive in one or more SLNs (sensitivity 67 %, false-negative rate 33 %). On the basis of the CK20 and MUC2 mRNA levels in SLNs, occult metastases were suggested in 86 (60 %) and 52 (36 %) of the 143 otherwise LN-negative (pN0) patients, respectively. Survival analysis with a median 3.6-year follow-up revealed that MUC2 mRNA quantification had significant prognostic value in SLNs from all patients; however, occult SLN metastasis detection did not.

Conclusions: Occult SLN metastases detected by CK20 and MUC2 mRNA quantification had limited prognostic value.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Keratin-20 / genetics*
  • Lymphatic Metastasis
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Mucin-2 / genetics*
  • Mutation / genetics
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Sentinel Lymph Node Biopsy*
  • Survival Rate
  • Young Adult
  • ras Proteins / genetics

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Keratin-20
  • MUC2 protein, human
  • Mucin-2
  • Proto-Oncogene Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins