Prognostic significance of occult metastases detected by sentinel lymphadenectomy and reverse transcriptase-polymerase chain reaction in early-stage melanoma patients.
OBJECTIVE
Detection of micrometastases in the regional tumor-draining lymph nodes is critical for accurate staging and prognosis in melanoma patients. We hypothesized that a multiple-mRNA marker (MM) reverse transcriptase-polymerase chain reaction (RT-PCR) assay would improve the detection of occult metastases in the sentinel node (SN), compared with hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC), and that MM expression is predictive of disease relapse.


METHODS
Seventy-two consecutive patients with clinical early-stage melanoma underwent sentinel lymphadenectomy (SLND). Their SNs were serially sectioned and assessed for MAGE-3, MART-1, and tyrosinase mRNA expression by RT-PCR, in parallel with H&E staining and IHC, for melanoma metastases. MM expression in the SNs was correlated with H&E and IHC assay results, standard prognostic factors, and disease-free survival.


RESULTS
In 17 patients with H&E- and/or IHC-positive SNs, 16 (94%) expressed two or more mRNA markers. Twenty (36%) of 55 patients with histopathologically negative SNs expressed two or more mRNA markers. By multivariate analysis, patients at increased risk of metastases to the SN had thicker lesions (P =.03), were 60 years of age or younger (P <.05), and/or were MM-positive (P <.001). Patients with histopathologically melanoma-free SNs who were MM-positive, compared with those who were positive for one or fewer mRNA markers, were at increased risk of recurrence (P =.02). Patients who were MM-positive with histopathologically proven metastases in the SN were at greatest risk of disease relapse (P =. 01).


CONCLUSIONS
H&E staining and IHC underestimate the true incidence of melanoma metastases. MM expression in the SN more accurately reflects melanoma micrometastases and is also a more powerful predictor of disease relapse than are H&E staining and IHC alone.
Bostick
P J
PJ
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, CA 90404, USA.
Morton
D L
DL
Turner
R R
RR
Huynh
K T
KT
Wang
H J
HJ
Elashoff
R
R
Essner
R
R
Hoon
D S
DS
D000328:Adult; D000367:Age Factors; D000368:Aged; D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm / Q000032:analysis; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000473:pathology*
D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger