Prognostic significance of the sequential detection of circulating melanoma cells by RT–PCR in high-risk melanoma patients receiving adjuvant interferon

Abstract

The purpose of this study was to address the prognostic significance of circulating melanoma cells by reverse transcriptasepolymerase chain reaction in the peripheral blood of stage IIB and III melanoma patients on high-dose adjuvant interferon at multiple sequential time points from initiation of treatment. Tyrosinase mRNA in peripheral blood from these patients was assayed by reverse transcriptase polymerase chain reaction prior to initiation of adjuvant interferon, at completion of 1 month of intravenous interferon and at 3 monthly intervals until progression. Four hundred and eighteen blood samples from 60 melanoma patients were analysed. The median follow-up time calculated from the time of inclusion in the study was 23 months (range 2 -38 months). Tyrosinase mRNA in blood was detected in 42 (70%) of 60 patients: 16 (76%) of 21 stage IIB patients and 26 (66% ) of 39 stage III patients. The presence of tyrosinase mRNA in blood was correlated with a shorter disease-free survival (P : 0.03) and in multivariante analysis was an indepent prognostic factor for relapse. Patients who seroconverted to a negative reverse-transcriptase-polymerase chain reaction after induction treatment had a significantly lower probability of recurrence. The presence of circulating melanoma cells is a marker of a high relapse risk and shorter disease-free survival whether detected postoperatively or during follow-up. Tyrosinase mRNA amplification by reverse-transcriptasepolymerase chain reaction may be a useful tool for monitoring the efficacy of adjuvant treatment in stage IIB and III melanoma patients.

Tyrosinase expression in the peripheral blood of stage III melanoma patients is associated with a poor prognosis: a clinical follow-up study of 110 patients

“…The association between tyrosinase results and clinical outcome is also demonstrated by the early detection of disease recurrence after a positive determination. In our experience, this interval is lower (median 1.9 months) than that reported by Gogas (21 months) (Gogas et al, 2002), even if, according to the study design, follow-up investigations were anticipated only at the patients' request or due to clinical doubt, and not on the basis of tyrosinase results. The metastatic pattern of relapse, with a higher incidence of visceral localisations in positive than in negative patients, confirms that tyrosinase expression is significantly associated with the haematogenous metastatic pathway.…”

“…Mellado et al (2002) reported similar results in a cohort of 50 stage III patients treated with adjuvant IFN, showing positive results in 12% before treatment and 46% during follow-up. On the other hand, Gogas et al (2002) found a higher percentage of positive results before treatment (50%) in 60 stage IIB -III disease-free patients.…”

“…The meta-analysis performed by Tsao et al (2001) suggests that, at the present time, RT -PCR for tyrosinase mRNA is of limited value given the unreliability of the procedure and the lack of data on the outcome of stage I -III positive patients. More recently, Mellado et al (2002) and Gogas et al (2002) showed that the detection of tyrosinase mRNA in disease-free melanoma patients treated with adjuvant interferon (IFN) is associated with an increased risk of relapse and shorter disease-free survival (DFS).…”

Reply: Value of tyrosinase RT–PCR in melanoma prognosis

“…at first presentation). In our work (Gogas et al, 2002), in 27 patients tested, one was already positive before operation becoming negative some time following operation' we would like to state that more than 95% of the patients referred to our Center have already been diagnosed with melanoma and require wide local excision, sentinel lymph node and consideration for adjuvant treatment. So, it was not possible to obtain blood from patients before any surgical manipulation.…”

Value of tyrosinase RNA detection by an RT–PCR method in melanoma prognosis

“…The paper published in Br J Cancer (2002, 87: 181 -186) on the prognostic significance of molecular detection of melanoma cells in melanoma patients under adjuvant interferon (Gogas et al, 2002) seems to be a continuation of the protocol we first applied in the same research laboratory utilizing the same facilities, the same methods and at least the same of some reagents (e.g. the ATTCC SK-mel-28 cells) we used in an analogous work.…”