Related Experiment Video
Updated: Jul 16, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Diagnostic utility of combining PRAME and HMB-45 stains in primary melanocytic tumors
Dusan Rasic1, Niels Korsgaard2, Niels Marcussen1
1Department of Pathology, Research Unit of Pathology, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark.
Background:
Pathologists face ongoing challenges distinguishing between benign and malignant melanocytic tumors. PRAME (PReferentially expressed Antigen in Melanoma) has a demonstrated value distinguishing between these types of lesions. However, the sensitivity of single immunohistochemistry is variable. HMB-45 is another valuable marker, but on its own, has a limited ability in setting of primary melanocytic tumors. This study sought to evaluate the diagnostic potential of a dual panel combining PRAME and HMB-45 in the assessment of primary melanocytic tumors.
Methods:
259 tumors, of which 141 were benign nevi, 31 dysplastic nevi (either low- or high grade dysplasia), and further 87 malignant melanomas, were retrieved from the department's archives and assessed by two experienced dermatopathologists. New sections were stained with PRAME and HMB-45, respectively. For PRAME, a nuclear, and for HMB-45, a cytoplasmic staining, was considered positive and scored as described in the literature on a scale from 0 to 4+. Only dermal component was assessed on HMB-45 stain.
Results:
PRAME was diffusely expressed in only 1 benign nevus, with focal expression in further 28 compared to 22 diffusely and 103 focally HMB-45-positive benign nevi. 5 high-grade dysplastic nevi showed diffuse PRAME expression in epidermal component, with varying degree of positivity in adjacent dermal compartment, and further 8 dysplastic nevi showed only focal expression. HMB-45 was diffusely expressed in only 2, with focal expression in 23, and no apparent positivity in remaining 6 dysplastic nevi. In invasive melanoma group, PRAME stained >75 % cells in 64/87 tumors, however, 10/87 melanomas were completely negative. HMB-45 was captured diffusely in 49/87 melanomas, 32 showed patchy expression, and 6 tumors were blank negative. Diffuse 4+ PRAME positivity showed superior sensitivity and specificity of 73,6 % and 96,5 %, respectively, compared to HMB-45, 56,3 % and 86,0 %, respectively. No nevi showed double 4+ positivity, however, the sensitivity for double positivity was only 49,4 %.
Conclusion:
Our results confirm the superiority of PRAME over HMB-45 in the differential diagnosis of melanocytic tumors. However, combined staining can significantly increase specificity, rendering a benign diagnosis more unlikely in a double 4+ diffuse positivity setting.
Insights
PRAME is superior to HMB-45 for diagnosing melanocytic tumors, offering higher sensitivity and specificity. Combining PRAME and HMB-45 (PReferentially expressed Antigen in Melanoma) improves diagnostic accuracy, especially in differentiating benign from malignant lesions.
Area of Science:
- Dermatopathology
- Oncology
- Immunohistochemistry
Background:
- Distinguishing benign from malignant melanocytic tumors is challenging for pathologists.
- PRAME and HMB-45 are established immunohistochemical markers, but single-marker sensitivity can be variable.
- This study investigates the combined diagnostic utility of PRAME and HMB-45.
Purpose of the Study:
- To evaluate the diagnostic performance of a dual immunohistochemical panel combining PRAME and HMB-45.
- To assess the effectiveness of this panel in the differential diagnosis of primary melanocytic tumors.
- To compare the diagnostic accuracy of the combined panel against individual markers.
Main Methods:
- 259 melanocytic tumors (141 nevi, 31 dysplastic nevi, 87 melanomas) were stained for PRAME (nuclear) and HMB-45 (cytoplasmic).
- Immunohistochemical staining was scored on a scale of 0 to 4+ by two dermatopathologists.
- Only the dermal component was assessed for HMB-45 positivity.
Main Results:
- PRAME demonstrated higher sensitivity (73.6%) and specificity (96.5%) than HMB-45 (56.3% sensitivity, 86.0% specificity) for melanoma diagnosis.
- While no benign nevi showed double 4+ positivity, the combined panel's sensitivity for this finding was 49.4%.
- PRAME showed diffuse expression in 73.6% of melanomas, while HMB-45 was diffusely positive in 56.3%.
Conclusions:
- PRAME is a more effective marker than HMB-45 for the differential diagnosis of melanocytic tumors.
- A combined PRAME and HMB-45 staining panel can enhance diagnostic specificity.
- Dual 4+ positivity in the combined panel strongly suggests a malignant diagnosis, reducing the likelihood of a benign lesion.
