The Sporadic Nature of Shedding Cells in Blood: Multiple RNA Diagnostic Testing and Prognostication of Cancer Progression

The biological cascade of cancer progression starts from uncontrolled proliferation of cells to generate a tumor mass. The enlarging tumor acquires vasculature through which malignant cells detach from the primary site and disseminate into blood, invade adjacent tissues, and ultimately form metastases at distant sites. The circulating tumor load in blood can thus provide an index of tumor progression to identify the risk for developing malignancies. Since Smith et al. (1) reported the detection of circulating melanoma cells (CMCs) in blood by reverse transcription-PCR (RT-PCR), this line of investigation has been pursued by researchers aiming at early detection of cancer cells in blood, bone marrow, lymph nodes, or sentinel nodes for predicting cancer progression (2). Unexpectedly, contradictory results were obtained relating to the diagnostic and prognostic implications of circulating tumor cells (CTCs). RT-PCR positivity for tyrosinase (TYR) mRNA in lymph nodes, but not that in blood, predicts relapse and correlates with the Breslow thickness, a well-documented prognosticator (3)(4)(5). The CMCs are possibly intermittently shed into blood, or hematogenous dissemination occurs in a small proportion of melanoma patients. Although tumor cells transiently persist in blood, the rate of CMC detection in blood has been associated with tumor stage, relapse, and disease-free survival (6)(7). In this issue of Clinical Chemistry , Szenajch et al. (8) have focused on the prognostic implication of multiple RT-PCR testing for TYR mRNA in blood of melanoma patients. TYR is a key enzyme involved in the melanin biosynthetic pathway; thus TYR mRNA is presumably a tissue-specific marker for detecting CMCs or healthy melanocytes in blood. However, cells in other tissues also express TYR mRNA, and the assumption of the entire absence of healthy melanocytes in blood of melanoma patients may not be true. RT-PCR results are extremely variable and sometimes …