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New test may improve methods for detecting recurrence of colon cancer

Scott Gottlieb New York

In patients with apparently node negative colorectal cancer, the presence of a specific protein may be a more accurate marker of recurrence after surgical resection than currently used markers, according to the results of a new study.

The lead author, Dr Scott Waldman, and his colleagues at Thomas Jefferson University in Philadelphia looked at 21 patients with histologically confirmed node negative colorectal cancer who had undergone resection. Sections of paraffin-embedded lymph nodes were obtained from each patient and were pooled, and their RNA was analysed by reverse transcriptase polymerase chain reaction.

The protein known as guanylyl cyclase C messenger RNA (GCC mRNA) was found in the lymph nodes of all of the 10 patients who had recurring cancer within three years of surgery. Moreover, the protein did not show up in any of the samples taken from the 11 patients who were free of disease for six years or more after surgery (Annals of Internal Medicine 1999;131:805-12).

"The current state of the art for staging colorectal cancer is good, but it is not perfect. This imperfect approach sometimes results in patients being diagnosed with a lower stage of disease than they actually have. This is not a reflection of errors but, rather, the insensitivity of the current standard techniques being employed," Dr Waldman said.

The authors note that, given the prognostic and therapeutic importance of staging, accurate histopathological evaluation of lymph nodes to detect tumour cells is crucial.

However, conventional methods for examining lymph nodes microscopically have limitations. For example, it can be difficult to differentiate single or even small clumps of tumour cells from other types of cells, according to the authors.

In addition, the standard practice of examining only a limited number of tissue sections from each lymph node can omit from review as much as 99% of each specimen and can introduce sampling error.

Recurrence after surgery for colon cancer is a major problem and is often the ultimate cause of death. After treatment of colon cancer, periodic evaluations have long been believed to lead to the earlier identification and management of recurrent disease.

However, the impact of such monitoring on overall mortality of patients with recurrent cancer has been limited by the relatively small proportion of patients in whom localised, potentially curable metastases is found.

To date, there have been no large scale randomised trials documenting the efficacy of a standard, postoperative monitoring programme. The test used by the authors of this study is currently being developed into a blood test that can detect microscopic deposits of cancer cells in patients with colorectal cancer, said Dr Waldman, in hopes of using GCC mRNA to detect any cancer recurrences much earlier than previously possible.

The test results are considered preliminary because there were only 21 patients involved in the study. Dr Waldman plans to enroll 1000 to 2000 patients in a larger, five year study that will compare the predictive ability of the standard examination of lymph nodes to that of the GCC marker test to predict the recurrence of disease.  
 

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