Genetic ID of marker in lymph nodes may be linked to colorectal cancer recurrence risk

A preliminary report suggests that genetic testing may help identify a marker in lymph nodes that is associated with an increased risk of colorectal cancer recurrence among patients in whom conventional testing indicates that those lymph nodes show no evidence of cancer spread, according to a study in the February 18 issue of JAMA.

Metastasis of tumor cells to regional lymph nodes is the single most important prognostic factor in patients with colorectal cancer. Recurrence rates increase from approximately 25 percent in patients with lymph nodes free of tumor cells as determined by biopsy (pN0 colorectal cancer) to approximately 50 percent in patients with four or more lymph nodes with metastases, according to background information in the article.

"Given the established relationship between lymph node metastasis and prognosis, recurrence in a substantial fraction of patients with pN0 colorectal cancer suggests the presence of occult [undetected] metastases (pN0 [mol+]) in regional lymph nodes that escape [biopsy] detection. Conversely, patients with pN0 colorectal cancer who are free of lymph node metastases may be at lowest risk for developing recurrent disease. Thus, a more accurate assessment of occult metastases in regional lymph nodes in patients with pN0 colorectal cancer could improve risk stratification in this clinically heterogeneous population," the authors write.

Research suggests that guanylyl cyclase C (GUCY2C), an intestinal tumor suppressing receptor, is a specific molecular marker for metastatic colorectal cancer that could reveal occult metastases in lymph nodes and better estimate recurrence risk.

Scott A. Waldman, M.D., Ph.D., of Thomas Jefferson University, Philadelphia, and colleagues examined the association of colorectal cancer recurrence with occult lymph node metastases detected by measuring GUCY2C messenger RNA, using the reverse transcriptase–polymerase chain reaction (RT-PCR; a highly sensitive technique for the detection and measurement of quantity of messenger RNA). The study included 257 patients with pN0 colorectal cancer who provided 2,570 lymph nodes for biopsy and GUCY2C messenger RNA analysis. Patients were followed up for a median (midpoint) of 24 months for disease recurrence or death.

"In this study, prospective detection of occult metastases by GUCY2C quantitative RT-PCR appeared to be an independent prognostic marker of risk. Molecular staging revealed that about 13 percent of patients with pN0 colorectal cancer were free of tumor cells, while about 87 percent had GUCY2C results that suggested occult metastases," the researchers write. "Future studies with greater numbers of patients should provide more precise estimates of the prognostic utility of GUCY2C quantitative RT-PCR."

"Molecular staging could overcome limitations in the detection of occult lymph node metastases by incorporating all available tissue into analyses and increasing detection sensitivity through quantifiable disease-specific molecular markers, which nominally identify a single cancer cell in 1 million normal cells."

The authors add that molecular staging represents one component of a comprehensive diagnostic, prognostic and predictive strategy to personalize management strategies for individual patients.


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