Prognostic value of circulating melanoma cells detected by reverse transcriptase-polymerase chain reaction.
OBJECTIVE
Factors that are predictive of prognosis in patients who are diagnosed with malignant melanoma (MM) are widely awaited. Detection of circulating melanoma cells (CMCs) by reverse transcriptase-polymerase chain reaction (RT-PCR) has recently been postulated as a possible negative prognostic factor. Two main questions were addressed: first, whether the presence of CMCs, defined as the patient being positive for any of the three markers, had a prognostic role; and second, what the predictive value of each individual marker was.


METHODS
A consecutive series of 200 melanoma patients observed between January 1997 and December 1997, with stage of disease ranging from I to IV, was analyzed by semiquantitative RT-PCR. Tyrosinase, p97, and MelanA/MART1 were used as markers to CMCs on baseline peripheral blood samples. Progression-free survival (PFS) was used as a unique end point and was described by the product limit method. Multivariable analysis was applied to verify whether the auspicated prognostic value of these markers was independent of the stage of disease, and a subgroup analysis was performed that excluded patients with stage IV disease.


RESULTS
Overall, 32% (64 of 200) of patients progressed, and a median PFS of 52 months in the whole series was observed. The presence of CMCs and the markers individually or combined was predictive of prognosis in the univariate analysis but did not provide additional prognostic information to the stage of disease in multivariable models. In the subgroup analysis of stage (ie, I-III subgroup), similar results were observed.


CONCLUSIONS
Detection of CMCs in peripheral blood samples at the time of MM diagnosis by semiquantitative RT-PCR does not add any significant predictive value to the stage of disease. Thus, this approach should not be used in clinical practice, and further studies are required to determine its usefulness.
Palmieri
Giuseppe
G
Institute of Genetics of Populations, Consiglio Nazionale delle Ricerche, Alghero (Sassari), Italy.
Ascierto
Paolo A
PA
Perrone
Francesco
F
Satriano
Sabrina M R
SM
Ottaiano
Alessandro
A
Daponte
Antonio
A
Napolitano
Maria
M
Caracò
Corrado
C
Mozzillo
Nicola
N
Melucci
Maria T
MT
Cossu
Antonio
A
Tanda
Francesco
F
Gallo
Ciro
C
Satriano
Rocco A
RA
Castello
Giuseppe
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000175:diagnosis; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D018365:Neoplasm, Residual / Q000097:blood; D009360:Neoplastic Cells, Circulating; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000097:blood* / Q000175:diagnosis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D058965:MART-1 Antigen; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014442:Monophenol Monooxygenase