Published in Cancer Detection and Prevention 2000; 24(1):72-79.

Evidence for Colorectal Cancer Micrometastases using RT-PCR Analysisof MUC2 in Lymph Nodes

Andrea Bernini1, Michael Spencer1, Sandra Frizelle, Robert D.Madoff1, Larry B. Willmott3,4, Stanley R. McCormick4, Gloria A.Niehans3, Samuel B. Ho2, and Robert A. Kratzke2

Departments of Surgery1, Medicine2, and Laboratory Medicine3, Minneapolis VA Medical Centerand the University of Minnesota Medical School, Minneapolis, MN 55417, and the Department ofPathology4, United Hospital, St. Paul, MN 55102

Address all correspondence to: RobertA. Kratzke, MD. 111E Section of Hematology/Oncology Minneapolis VA Medicat Center,1 Veterans Drive, Minneapolis, MN 55417

ABSTRACT Poor survival in patients following resection for early stage colorectal cancer is thought to be due inpart to the presence of occult micrometastases at the time of surgery. The MUC2 mucin gene is highly expressed inthe colon and associated colorectal tumors and may be a candidate marker for colorectal cancer micrometastases.We have used RT-PCR to detect expression of MUC2 mRNA transcripts in order to identify possible lymph nodemicrometastases in node negative (Stage I and II, or Dukes A and B) colorectal cancer patients. A total of 396 nodes(histologic stage NO) from 34 colort and nine rectal cancers were studied by RT-PCR analysis with nested primersfor MUC2 (an average of 7.6 nodes per case). In the primary tumors, 42/43 (98.1%) were positive for MUC2 byRT-PCR. Evidence of the presence of MUC2 was demonstrated in nodes from Oof 10(0%) patients with Tis or TI,one of six (16.7%) from 12, 10 of 25 (40.0%) from T3, and one of two (50%) from 14 tumors. MUC2 RTPCR wasnegative in six rtodes from three patients wtth non-malignant colon disease and positive in ltistologically positivelymph nodes from six of six (l00%) stage Ill colon cancers. In this study. using RT-PCR to (letect the presence ofMUC2 transcripts, we have found preliminary evidence for possible micrometastatic disease in approximately athird of histologically negative NO colorectal cancer patients. The increased presence of MUC2 expression alsocorrelated with more advanced T stage. We conclude that MUC2 RT-PCR may be a sensitive and specific ntarkerfor occult micrometastases. This technique has the potential to identify a group of colorectal cancer patients at riskfor early cancer recurrence.

KEY WORDS: micrometastases, colon cancer, .

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