Volume 3 Number 1 - September 8, 1997
Tyrosinase is an enzyme of melanin synthesis found only in
melanin-producing cells. Melanin producing cells are not normally found in
the peripheral blood. The presence of tryosinase messenger RNA (mRNA) in
the peripheral blood of melanoma patients is an indicator of circulating
melanoma cells.1 The reverse transcription-polymerase chain
reaction based assay (RT-PCR) for tyrosinase mRNA is highly sensitive,
allowing detection of 1 melanoma cell in 5 cc of blood. The presence of
peripheral blood tyrosinase mRNA by RT-PCR has been demonstrated to
correlate with the clinical stage of melanoma and survival. In stage II-II
melanoma patients, the recurrence rate and disease-free survival were
significantly worse in patients positive for peripheral blood tyrosinase
mRNA by RT-PCR.2,3
Adjuvant therapy is being strongly promoted for melanoma patients
thought to be at risk for metastatic disease.4 Traditionally,
patients with Stage I melanoma of intermediate (Breslow thickness 1.5mm to
4 mm) and advanced (Breslow thickness > 4 mm) thickness have been
considered candidates for adjuvant therapy. The recent results of
interferon trials have encouraged the use of adjuvant therapy for melanoma
patients with thinner melanomas. Interferon treatment is particularly
helpful to patients with local lymph node metastasis. 5
Sentinel lymph node biopsy is being advocated as a staging tool to detect
early metastasis and identify patients who might benefit from adjuvant
therapy. Traditional laboratory and radiographic tests for monitoring
melanoma patients have not been shown to be of special value in early
detection of metastatic disease. Newly developed methods which may be of
value in detecting or predicting recurrence include peripheral blood
tyrosinase mRNA and the PET scan.
Molecular Pathology Laboratory of Maryville, Tennessee, under the
direction of Dr. Roger Hubbard, has developed a RT-PCR tyrosinase assay.
Blood samples from melanoma patients are being sought to begin validating
the clinical utility of the assay. In these early phases of development,
blood samples from patients with metastatic melanoma are particularly
needed. Two 5 cc purple topped tubes (EDTA) are requested from each
patient. Specific directions for submitting samples may be obtained by
calling Molecular Pathology Laboratory, 423-981-2332.
Patients with melanoma are also being sought for a study "Tyrosinase
mRNA amplification and Positron Emission Tomography (PET) for detecting
Recurrent or Metastatic Melanoma." This study, under the direction of
Dr. Karl F. Hubner ,University of Tennessee Medical Center Knoxville, PET
Center, aims to use the RT-PCR tyrosinase mRNA assay and FDG PET scan to
identify early metastasis in melanoma patients. For more information or to
enroll a patient in this study, call Dr. Karl Hubner,
423-544-9662.
>Two recent papers have suggested that the RT-PCR tyrosinase mRNA assay
is not sensitive enough to be used as a progression marker or to monitor
the effect of therapy. 6,7 None the less, it may still be of
sufficient predictive value to identify melanoma patients who may benefit
from adjuvant therapy or additional imaging studies such as PET scan. It
is very exciting to have PET scan and the RT-PCR tyrosinase mRNA assay
available for melanoma patients in our region. By participating in these
preliminary studies, we may be able to significantly improve the care of
our melanoma patients.
PBG
RT-PCR tyrosinase mRNA assay
Dr. Roger
Hubbard
Molecular Pathology Laboratory
424 E. Church
Avenue
Maryville, Tennessee 37804
Blood samples from melanoma patients
Two 5 cc purple topped tubes
(EDTA) are requested from each patient.
Phone 423-981-2332
Tyrosinase mRNA amplification and Positron Emission Tomography (PET)
for detecting Recurrent or Metastatic Melanoma
Dr. Karl F. Hubner
PET Center
University of Tennessee Medical Center
1924 Alcoa
Highway
Knoxville, Tennessee 37920
Phone 423-544-9662.
References
1. Stevens GL, Scheer WD, Levine EA. Detection of
tyrosinase mRNA from the blood of melanoma patients. Ca Epidemiol
Biomarkers & Prevention. 5:293-296, 1996.
2. Kunter U et al. Peripheral blood tyrosinase messenger RNA detection
and survival in malignant melanoma. J Natl Cancer Inst 88:590-594,
1996.
3. Mellado B. et al. Detection of circulating neoplastic cells by
reverse-transcriptase polymerase chain reaction in malignant melanoma:
association with clinical stage and prognosis. J Clin Oncol 14:2091-2097,
1996.
4. Demierre MR, Koh HK. Adjuvant therapy for cutaneous malignant
melanoma. J Am Acad Dermatol 36:747-764, 1997.
5. Kirkwood JM, et al. Interferon alfa-2b adjuvant therapy of high-risk
resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial
EST 1684. J Clin Oncol 14:7-17, 1996.
6. Glaser R et al. Detection of circulating melanoma cells by specific
amplification of tyrosinase complementary DNA is not a reliable tumor
marker in melanoma patients: a clinical two-center study. J Clin Oncol
15:1218-2825, 1997.
7. Jung FA et al. Evaluation of tyrosinase mRNA as a tumor marker in
the blood of melanoma patients. J Clin Oncol 15:2826-2831,
1997.
Dermpath Update
Paul B. Googe,
M.D., Editor
Knoxville Dermatopathology Laboratory
315 Erin Drive
Knoxville, Tennessee 37919
Phone 423-584-1933
FAX 423-584-1323
Toll Free 1-800-772-0951
www.labpath.com
