Molecular detection of metastatic melanoma cells in cerebrospinal fluid in melanoma patients.

Melanoma frequently metastasizes to the central nervous system (CNS). The diagnosis of CNS metastases typically is made following the onset of clinical symptoms. Thus, more sensitive diagnostic approaches are needed to identify subclinical CNS metastases. Currently, standard cytologic analysis of the cerebrospinal fluid (CSF) is limited by its poor sensitivity. A more sensitive assay was therefore developed using multiple reverse transcriptase-polymerase chain reaction (RT-PCR) markers. CSF was collected and assessed by RT-PCR for three known melanoma-associated markers (MAGE-3, MART-1, and tyrosinase) to detect occult metastatic melanoma cells in the CSF of 37 American Joint Committee on Cancer (AJCC) stage IV melanoma patients. Cytologic analysis of CSF was performed on all patients, and immunohistochemistry (IHC) analysis was performed on 33 CSF samples using anti-S100 and anti-HMB-45 antibodies. Only one patient (3%) had tumor-positive CSF cytology and IHC upon entry into the study, whereas 12 patients (32%) were positive for at least one RT-PCR marker. The correlation between CSF RT-PCR positivity of MART-1 and/or MAGE-3 and the development of CNS metastases at 3 mo was significant (p = 0.04). Fifteen of 37 patients (41%) had either positive MRI and/or positive RT-PCR results. Multimarker RT-PCR is more informative and sensitive than cytology/IHC in assessing the CSF of melanoma patients.