Intestinal-specific marker may predict colorectal cancer metastases

AACR Molecular Diagnostics in Cancer Therapeutic Development

The presence of a specific protein in the lymph nodes could indicate metastatic disease in patients with colorectal cancers, according to data presented by Scott A. Waldman, MD, PhD.

Waldman presented the data at the Third American Association for Cancer Research International Conference on Molecular Diagnostics in Cancer Therapeutic Development in Philadelphia. He and colleagues have been researching the role of guanylyl cyclase c (GCC), a protein produced by intestinal cells, in colorectal cancers.

“It turns out that GCC has a number of interesting qualities and characteristics that are useful for managing patients with colorectal cancer,” said Waldman, professor and chair of pharmacology and experimental therapeutics at Jefferson Medical College of Thomas Jefferson University in Philadelphia. “One of them is that the only place GCC is made in the entire body is in the intestine. Interestingly, when intestinal epithelial cells undergo transformation and become colon cancer cells, those cancer cells continue to make GCC. When they metastasize to different sites, including lymph nodes, they continue to make GCC.” That means that GCC may be used as a molecular marker to identify pockets of metastatic cells, he said.

Researchers from nine centers prospectively enrolled 257 patients with node-negative colorectal cancer in a study. Patients were followed for a median of 45 months and tested for time to recurrence and disease-free survival. Thirty-two patients (12.5%) tested negative for GCC in their lymph nodes; all but two were recurrence free during follow-up. Two hundred twenty-five patients (87.5%) tested positive for GCC in their lymph nodes. Among those, 20.9% developed recurrent disease (P=.006). These results indicated that GCC is independently associated with time to recurrence and disease-free survival in this patient population.

Waldman said that the research into GCC may eventually reveal a role for the protein in the primary prevention of colorectal cancers, in risk stratification of patients already diagnosed and possibly in vaccine immunotherapy. – by Leah Lawrence

These preliminary data suggest that the presence of the protein guanylyl cyclase c in pathologically negative lymph nodes may, in essence, turn the lymph node positive in terms of staging. This factor can be added to numerous other potential prognostic features — loss of heterozygosity of 18Q, MSS — that need to be studied prospectively to determine if we can improve on classic pathologic staging.

– Alan P. Venook, MD

HemOnc Today Editorial Board member

For more information:

Waldman SA. #A36. Presented at: the Third AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development; Sept. 22-25, 2008; Philadelphia.