Human high molecular weight-melanoma-associated antigen: utility for detection of metastatic melanoma in sentinel lymph nodes.
OBJECTIVE
Detection of micrometastasis in melanoma-draining lymph nodes is important for staging and prognosis. Immunohistochemical staining (IHC) using S-100p-HMB-45-, and MART-1-specific antibodies is used for detecting metastases in sentinel lymph nodes (SLN). However, improvement in IHC is needed for melanoma micrometastasis detection.


METHODS
Paraffin-embedded archival tissue (PEAT) specimens were obtained from 42 non-SLN macrometastases, 42 SLN metastases, and 16 tumor-negative SLNs of 100 melanoma patients who underwent SLN biopsy. PEAT specimens were assessed by IHC with high molecular weight-melanoma-associated antigen (HMW-MAA)-specific monoclonal antibodies (mAb) and with S-100p-, HMB-45-, and MART-1-specific antibodies. Quantitative real-time reverse-transcriptase PCR assay was used for HMW-MAA and MART-1 mRNA detection.


RESULTS
Expression frequency and immunostaining intensity were higher for HMW-MAA than MART-1 in nodal macrometastases (P < 0.0001 and P < 0.0001, respectively) and micrometastases (P < 0.0001 and P = 0.004, respectively). All 52 (100%) macrometastases were positive with HMW-MAA-specific mAbs, whereas 43 (83%) were positive with MART-1-specific mAbs. In a comparison analysis, 23 of 23 (100%) micrometastases were HMW-MAA-positive, whereas 21 (91%) and 18 (78%) specimens were S-100p- and HMB-45-positive, respectively. Quantitative real-time reverse-transcriptase PCR analysis of 48 nodal metastases showed HMW-MAA mRNA detection in SLNs with metastases.


CONCLUSIONS
HMW-MAA is more sensitive and specific than MART-1, S-100p, and HMB-45 for IHC-based detection of SLN micrometastases. SLN PEAT-based detection specificity of melanoma micrometastases can be improved by IHC with HMW-MAA-specific mAbs.
Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA.
Yasufumi
Y
Goto
Soldano
S
Ferrone
Takaaki
T
Arigami
Minoru
M
Kitago
Atsushi
A
Tanemura
Eiji
E
Sunami
Sandy L
SL
Nguyen
Roderick R
RR
Turner
Donald L
DL
Morton
Dave S B
DS
Hoon
D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D058965:MART-1 Antigen; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000096:biosynthesis; D016612:Paraffin Embedding; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D000099216:Chondroitin Sulfate Proteoglycan 4
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D058965:MART-1 Antigen; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000099216:Chondroitin Sulfate Proteoglycan 4; C548667:MLANA protein, human; C103003:S100P protein, human