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Human High Molecular Weight–Melanoma-Associated Antigen: Utility for Detection of Metastatic Melanoma in Sentinel Lymph Nodes

Authors' Affiliations: ¹ Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California; ² Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California ³ Department of Surgical Pathology, Saint John's Health Center, Santa Monica, California; and ⁴ University of Pittsburgh Cancer Institute, Departments of Surgery, Immunology and Pathology, Pittsburgh, Pennsylvania

Requests for reprints: Dr. Dave S.B. Hoon, Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404. Phone: 310-449-5267; Fax: 310-449-5282; E-mail: hoon{at}jwci.org.

Purpose: 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–specfic antibodies is used for detecting metastases in sentinel lymph nodes (SLN). However, improvement in IHC is needed for melanoma micrometastasis detection.

Experimental Design: 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.