The potential of cytokeratin 20 and mucin 2 mRNA as metastasis markers in regional lymph nodes of colon cancer patients investigated by quantitative RT-PCR.

PURPOSE

The presence of regional lymph node metastases is one of the most important prognostic factors in colon cancer. Nevertheless, up to 30% of the lymph node negative patients experience disease recurrence. Possibly, this patient group may be identified by more sensitive techniques than routine histopathological examination of the lymph nodes.

METHODS

In the present study, we have evaluated the detection of colon cancer lymph node metastases by real-time RT-PCR quantitation of the epithelial-specific cytokeratin 20 (CK20) and mucin 2 (MUC2) mRNAs.

RESULTS

Both assays were able to detect dilutions of tumor cells down to one tumor cell in 10(6) normal lymphocytes. CK20 and MUC2 mRNA were quantitated in 52 normal lymph nodes from 12 patients undergoing surgery for benign bowel diseases and in 144 primary colon tumors. The median tumor level of both markers were more than 10(4)-fold higher than the highest level in normal lymph nodes, indicating that the markers had a potential for metastasis detection in a clinical context. We applied the assays to 61 lymph nodes with known metastases detected by routine staining. Elevated CK20 or MUC2 mRNA levels were detected in 57 (95%) of the 61 LNs.

CONCLUSIONS

Thus, CK20 and MUC2 quantitation by real-time RT-PCR seems to be a promising, sensitive tool to detect metastases in regional lymph nodes from colon cancer patients.