Evidence for colorectal cancer micrometastases using reverse transcriptase-polymerase chain reaction analysis of MUC2 in lymph nodes

Poor survival in patients following resection for early stage colorectal ca ncer is thought to be due in parr to the presence of occult micrometastases at the time of surgery. The MUC2 mucin gene is highly expressed in the col on and associated colorectal tumors and may be a candidate marker for color ectal cancer micrometastases. We have used RT-PCR ro detect expression of M UC2 mRNA transcripts in order to identify possible lymph node micrometastas es in node negative (Stage I and II, or Dukes A and B) colorectal cancer pa tients. A total of 396 nodes (histologic stage NO) from 34 colon and nine r ectal cancers were studied by RT-PCR analysis with nested primers for MUC2 tan average of 7.6 nodes per case). In the primary turners, 42/43 (98.1%) w ere positive for MUC2 by RT-PCR. Evidence of the presence of MUC2 was demon strated in nodes from 0 of 10 (0%) patients with Tis or T1, one of six (16. 7%) from T2, 10 of 25 (40.0%) from T3, and one of two (50%) from T4 tumors. MUC2 RT-PCR was negative in six nodes from three patients with non-maligna nt colon disease and pos itive in histologically positive lymph nodes from six of six (100%) stage III colon cancers. In this study, using RT-PCR to d etect the presence of MUC2 transcripts, we have found preliminary evidence for possible micrometastatic disease in approximately a third of histologic ally negative NO colorectal cancer patients. The increased presence of MUC2 expression also correlated with more advanced T stage. We conclude that MU C2 RT-PCR may be a sensitive and specific marker for occult micrometastases . This technique has the potential ro identify a group of colorectal cancer patients at risk; for early cancer recurrence.