Predictive value of genetic diagnosis for cancer micrometastasis: histologic and experimental appraisal

The recently introduced genetic diagnosis of cancer micrometastasis is quite attractive because of its high detection sensitivity. Not infrequently, however, there are marked discrepancies between genetic and conventional histologic diagnoses, especially concerning lymph nodes from colon carcinoma patients. Because the histologic approach has long been relied on in the clinic, the reasons for the differences in results need to be elucidated.

Serial sections of genetic diagnosis positive but histologic negative lymph nodes of colon carcinoma patients were prepared for histologic and immunohistochemical studies. To investigate the possible contaminating influence of DNA sequences derived from degraded carcinoma cells from the primary site through the lymphatics, the authors also injected purified DNA of human colon carcinoma cells (SW480) into the foot pads of rats and sequentially examined lymph nodes using genetic diagnosis methodology.

Careful histologic examination of genetic diagnosis positive, histologically negative lymph nodes of colon carcinoma patients confirmed the absence of cancer cells, whereas p53 protein was immunohistochemically demonstrated to be present in the cytoplasm of sinus histiocytes. In the rat experiment, positive reactions were obtained with the inguinal lymph nodes beginning 30 minutes after the injection, and lymph nodes at various sites were subsequently affected, even after a 72-hour period.

The current study thus suggests that positive results with genetic diagnosis may simply indicate the presence of tumor DNA and do not necessarily mean that viable cancer cells are present. Although the genetic approach may still hold promise for the detection of cancer micrometastases, its predictive value should be carefully assessed clinicopathologically, because its supersensitivity may be associated with a greatly increased false-positive rate.