Prognostic significance of molecular staging study of sentinel lymph nodes by reverse transcriptase-polymerase chain reaction for tyrosinase in melanoma patients.
BACKGROUND
We performed this study to evaluate the clinical effect of microscopic and submicroscopic metastases in sentinel lymph nodes (SLNs) from patients with early-stage melanoma.


METHODS
Patients with confirmed cutaneous melanoma (American Joint Committee on Cancer stages I and II) underwent standard lymphoscintigraphy and SLN biopsy. Serial sections were divided between routine histopathology with hematoxylin and eosin plus immunohistochemistry for HMB-45 and molecular analysis by nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase (using beta-actin as a control).


RESULTS
Of 180 patients analyzed (318 SLNs), 38 (21%) patients had positive SLN(s) by routine hematoxylin and eosin and immunohistochemistry (microscopic disease; group 1), and 142 (79%) had negative histological results. Analysis by RT-PCR detected tyrosinase in at least 1 SLN from 124 (69%) patients. Among patients with histologically negative SLN(s), tyrosinase was detected in 86 (48%) patients (submicroscopic disease; group 2), whereas 40 (22%) patients had negative results by both histology and RT-PCR (group 3). Sixteen (9%) patients had histologically negative SLNs and ambiguous RT-PCR results (group 4). Among 138 patients in the analysis of recurrence (mean follow-up, 45 months), only 18 patients had a recurrence: 11 (31%) of 35 in group 1, 5 (10%) of 51 in group 2, and 2 (5%) of 37 in group 3. No recurrences were seen in group 4. Only group 1 had a significantly shorter disease-free survival and overall survival compared with the other groups.


CONCLUSIONS
After a long follow-up period, molecular upstaging by tyrosinase RT-PCR failed to detect a subgroup of patients with an increased probability of recurrence.
Mangas
Cristina
C
Department of Dermatology, Hospital Universitario Germans Trias i Pujol, Carretera Canyet s/n., 08916, Badalona, Spain.
Hilari
Josep M
JM
Paradelo
Cristina
C
Rex
Jordi
J
Fernández-Figueras
Maria Teresa
MT
Fraile
Manel
M
Alastrue
Antoni
A
Ferrándiz
Carlos
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics* / Q000556:secondary; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014442:Monophenol Monooxygenase