β Scribed by Andrea Abati; Lance A. Liotta
No coin nor oath required. For personal study only.
he identification of circulating tumor cells (CTC) in patients har-T boring malignant neoplasms has historically been an enigma. '-3 Initially, the main problem was definitive identification of the tumor cells. Currently, due to the powerful polymerase chain reaction (PCR), the identification of these cells is no longer the problem. There is no need for pathologists to laboriously screen samples hoping to find the "one in a million" malignant cell, and pray that they are not overcalling a hyperactive monocyte. The use of PCR to detect tumor specific mutations means that the "one in a million" malignant cell can be accurately identified."' The question that now arises is "What does this mean?" '~5.'
Ghossein and Rosai, in their informative report, discuss various PCR techniques used to determine the presence of CTC and minimal residual neoplastic disease (MRD).'.'"-" They describe identification of CTC and/or MRD through PCR based techniques utilizing PCR amplification of tumor specific DNA abnormalities (as in follicular lymphomas), and tissue specific or tumor specific mRNA (as in chronic myelogenous leukemia). They report that the various PCR based techniques are 10,000 x more sensitive than Southern blotting in the detection of MRD.5 Examples of the clinical utility of this technique include tracking of hematologic neoplasms with specific genetic alterations, and identification of MRD in epithelial malignancies (such as breast and prostate adenocarcinomas) or malignant melanoma, where the presence or absence of MRD can significantly alter therapy.5
The authors point out the limitations of interpreting ' ' g l a ~s . ' ' ~. ' ~ Routine lymph node histology following surgical dissections samples only 1% of the tissue submitted. This is a sobering statistic considering the therapeutic implications of micrometastases in numerous malignancies. PCR now provides a more sensitive and more specific method for identifying MRD. Now that we have the technology, what do we do with the information it yields? Ghossein and Rosai make no attempt to sweep the limitations of this technology under the rug. They address the false positives and false negatives associated with PCR t e ~h n o l o g y . ~, ~, ~~ On a clinical note, they review studies in which PCR based results for MRD and CTC correlate with tumor stage, tumor marker levels,
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