Molecular tool to identify hidden colorectal tumour cells

24 February 2009

Accurate prognosis of colorectal cancer is dependent upon assessment of the growth and spread of tumour cells. The current method for detecting spread of colorectal cancer to lymph nodes involves histological examination of samples of lymph node tissue in order to identify tumour cells. If tumour cells are detected, patients receive adjuvant chemotherapy in order to reduce the chances of the tumour recurring. However, as this method only examines samples of lymph node tissue, there is a possibility that occult (hidden) metastases may be present, resulting in disease recurrence in some patients whose histology results are negative for tumour cells.

Recently, a study by researchers at Thomas Jefferson University have shown that a molecular test may be a more sensitive means of identifying patients who have occult metastases (see press release). The test is based on examining the expression of a biomarker - guanylyl cyclase 2C (GUCY2C), an enzyme receptor that is selectively expressed by intestinal epithelial cells and over expressed by tumour cells. A previous study has shown an association between GUCY2C levels and colorectal cancer recurrence, suggesting it is a good biomarker [Cagir B et al. (1999) Ann. Intern. Med. 131(11):805-812].

In a new study, Waldman et al. examined the expression of GUCY2C in lymph node tissue of colorectal cancer patients in whom tumour cells were not identified by histopathology [Waldman SA et al. (2009) JAMA 301(7): 745-752]. They examined the levels of GUCY2C messenger RNA using reverse transcription PCR in samples from 227 patients and followed them over the course of approximately two years in order to assess disease recurrence. They found that 87.5% of these patients were positive for GUCY2C expression in at least one lymph node and follow-up indicated that 20.9% of those whose lymph nodes were positive for GUCY2C expression had disease recurrence in comparison with 6.3% who were negative for expression. In addition, in those who expressed GUCY2C, disease recurred after a shorter time and disease free-survival was also shorter. This prospective study corroborates the findings of the previous retrospective study, indicating a link between GUCY2C and disease recurrence. Furthermore, the study results suggest that monitoring GUCY2C expression may be a more sensitive means of detecting occult metastases and may aid in identifying those who might benefit from adjuvant chemotherapy, which is usually given to those who have metastases detected in lymph nodes by histopathology.

Comment: Methods to accurately assess tumour spread are important in determining the precise stage of the disease which in turn influences management of the condition. Molecular methods can be more sensitive than histopathological methods, having the capacity to detect one cancer cell in a million normal cells as opposed to one cancer cell for every two hundred normal cells. Molecular analysis requires the identification of suitable biomarkers and their validation. This study highlights a promising method to better stratify those with colorectal cancer and target treatment strategies. However, this test will have to be validated in a larger study in order to see if it truly does aid prognosis. In addition, only a small proportion of those expressed GUCY2C (20.9%) had recurrence of disease, suggesting that other factors may also influence disease recurrence.

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