A meta-analysis of reverse transcriptase-polymerase chain reaction for tyrosinase mRNA as a marker for circulating tumor cells in cutaneous melanoma

Objective: To systematically review the use of reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosinase messenger RNA as a molecular serum marker for metastatic melanoma. Data Sources: Computerized searches (1966-1999) of the PubMed and MDConsult databases and a manual search of retrieved article references. Study Selection: Cohort studies containing test subjects and negative controls were reviewed. Data Extraction: Three investigators independently screened abstracts for relevant studies and 2 investigators independently reviewed all eligible studies. Data Synthesist Of 127 identified studies, 50 were reviewed in detail and 23 met all inclusion criteria. From these 23 studies, the PCR methods, the total number of patients, the number of control subjects, and the number of RT-PCR-positive patients per stage were analyzed. Results of RT-PCR for tyrosinase messenger RNA were positive in 18% (95% confidence interval [CI],3%-22%) patients for stage I disease, 28% (95% CI, 23%-34%) for stage II disease, 19% (95% CI, 16%-21%) for stage I/II localized disease, 30% (95% CI, 26%-34%) for stage III disease, and 45% (95% CI, 41%-50%) for stage IV disease. Specificities were 100% in all but 1 study. Results of RT-PCR were positive in only 0.4% of healthy controls and patients with nonmelanoma cancer. Conclusions: The lack of data on the outcome of stage I, II, and III patients who were RT-PCR positive and the low prevalence of RT-PCR positivity in patients with known stage IV disease limit the applicability of this test at this lime. Ongoing and future studies on a quantitative RT-PCR, amplification of multiple melanoma-associated antigens, and use of the test as a prognostic indicator might improve the utility of this molecular serologic tool.