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HMB-45 detection in adenocarcinomas
C Hancock1, B C Allen, G A Herrera
1Department of Pathology, University of Mississippi Medical Center, Jackson 39216-4505.
Abstract:
Several studies have suggested that HMB-45 is a specific marker for melanoma, presumably due to its ability to detect a glycoprotein that is present in premelanosomes. The present study was conducted to evaluate whether HMB-45 is an absolutely specific antigenic determinant for melanoma and the role that testing with this antibody has in the differential diagnostic workup of amelanotic melanoma vs adenocarcinoma. Formaldehyde solution-fixed, paraffin-embedded tissue samples from 52 adenocarcinomas (primary or metastatic) and five melanomas (two primary and three metastatic) were immunostained with the use of a commercially available monoclonal antibody (MoAb), ie, HMB-45 (Enzo), a polyclonal antibody to S100 protein, a wide-spectrum keratin polyclonal antibody, and a keratin MoAb, ie, AE1/AE3. Approximately 10% (ie, 9.6%) of the adenocarcinomas (five cases) expressed HMB-45 with varied intensity and distribution. Positive primary tumors (n = 3) included one each from the breast, colon, and kidney; positive metastatic tumors (n = 2) included one each from the breast and endometrium. Fifty-two percent of the adenocarcinomas were positive for S100 protein. One renal carcinoma was negative for both keratins when tested with the AE1/AE3 MoAb and polyclonal antibody (Dako). This was the only adenocarcinoma that was negative when the keratin polyclonal antibody (Dako) was used. All but one additional adenocarcinoma demonstrated keratin expression when the AE1/AE3 MoAb was used for testing. This study showed that HMB-45 is not absolutely specific for melanoma. HMB-45 may react with some adenocarcinomas, at least when tested with the commercially available MoAb (Enzo). This fact, in conjunction with aberrant keratin expression by some melanomas and S100 protein expression by adenocarcinomas and other neoplasms other than melanomas, should be considered when antibody panels are evaluated in the workup of poorly differentiated tumors. However, HMB-45 appears to be the most specific marker that is available at the present time for supporting a diagnosis of melanoma.
Insights
The HMB-45 antibody is not absolutely specific for melanoma, as it can react with some adenocarcinomas. While HMB-45 remains the most specific marker for melanoma diagnosis, its limitations require careful consideration in differential diagnostics.
Area of Science:
- Oncology
- Immunohistochemistry
- Pathology
Background:
- HMB-45 is often considered a specific marker for melanoma, detecting a glycoprotein in premelanosomes.
- Its diagnostic utility in differentiating amelanotic melanoma from adenocarcinoma requires further evaluation.
Purpose of the Study:
- To assess the absolute specificity of HMB-45 as a melanoma marker.
- To determine the role of HMB-45 testing in the differential diagnosis of amelanotic melanoma versus adenocarcinoma.
Main Methods:
- Immunohistochemical staining of 52 adenocarcinomas and 5 melanomas using HMB-45, S100 protein, and keratin antibodies (AE1/AE3 and polyclonal).
- Analysis of HMB-45 reactivity in both primary and metastatic adenocarcinomas.
- Evaluation of keratin and S100 protein expression in adenocarcinomas and melanomas.
Main Results:
- Approximately 9.6% of adenocarcinomas (5 cases) expressed HMB-45.
- S100 protein was expressed in 52% of adenocarcinomas.
- Aberrant keratin expression was observed in some melanomas, and S100 protein in non-melanoma neoplasms.
Conclusions:
- HMB-45 is not absolutely specific for melanoma and can react with certain adenocarcinomas.
- Consideration of HMB-45 cross-reactivity, aberrant keratin expression in melanomas, and S100 protein expression in other tumors is crucial for antibody panel evaluation.
- HMB-45 remains the most specific available marker for supporting a melanoma diagnosis.