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Expression of microphthalmia transcription factor, S100 protein, and HMB-45 in malignant melanoma and pigmented nevi
Jianxin Xia1, Yanlong Wang1, Fuqiu Li1
1Department of Dermatology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Abstract:
Malignant melanoma (MM) is a type of malignant tumor, which originates from neural crest melanocytes. MM progresses rapidly and results in a high mortality rate. The present study aims to investigate the expression of microphthalmia transcription factor (MITF), the S100 protein, and HMB-45 in MM and pigmented nevi. A total of 32 MM samples (including three skin metastasis, three lymph node metastasis and two spindle cell MM samples), two Spitz nevus samples, four pigmented nevus samples and two blue nevus samples were collected. The expression levels of S100 protein, HMB-45, and MITF were observed via immunostaining. The S100 protein exhibited high positive rates in MM and pigment disorders (96.7 and 100%, respectively), but with low specificity. The S100 protein was also expressed in fibroblasts, myoepithelial cells, histocytes and Langerhans cells in normal skin samples. HMB-45 had high specificity. Its positive expression was only confined to MM cells and junctional nevus cells. Furthermore, HMB-45 was not expressed in melanocytes in the normal tissue samples around the tumor or in the benign intradermal nevus cells. MITF exhibited high specificity and high sensitivity. It was expressed in the nuclei of melanocytes, MM cells and nevus cells. It was observed to be strongly expressed in metastatic MM and spindle cell MMs. Thus, MITF may present as a specific immunomarker for the diagnosis and differential diagnosis of MM.
Insights
Microphthalmia transcription factor (MITF) shows high specificity and sensitivity, making it a potential diagnostic marker for malignant melanoma (MM). This study compared MITF, S100 protein, and HMB-45 expression in MM and benign nevi.
Area of Science:
- Oncology
- Dermatopathology
- Molecular Diagnostics
Background:
- Malignant melanoma (MM) is an aggressive skin cancer originating from melanocytes, characterized by rapid progression and high mortality.
- Accurate diagnosis and differential diagnosis of MM are crucial for effective treatment and improved patient outcomes.
- Immunohistochemical markers play a vital role in distinguishing MM from benign pigmented lesions.
Purpose of the Study:
- To investigate and compare the diagnostic utility of microphthalmia transcription factor (MITF), S100 protein, and HMB-45 in malignant melanoma and various benign pigmented nevi.
- To evaluate the specificity and sensitivity of these markers in differentiating MM from other skin lesions.
- To identify potential novel immunomarkers for MM diagnosis.
Main Methods:
- Immunohistochemical staining was performed on 32 MM samples (including metastatic and spindle cell variants) and 8 benign pigmented nevus samples (Spitz nevus, pigmented nevus, blue nevus).
- Expression levels of S100 protein, HMB-45, and MITF were analyzed in tumor cells and normal tissue.
- Quantitative and qualitative assessments of marker expression were conducted to determine diagnostic accuracy.
Main Results:
- S100 protein showed high positive rates in both MM and benign lesions but lacked specificity, being expressed in various normal skin cells.
- HMB-45 demonstrated high specificity, with positive expression limited to MM and junctional nevus cells, and absent in normal melanocytes and benign intradermal nevi.
- MITF exhibited both high specificity and sensitivity, with strong nuclear expression observed in MM cells, including metastatic and spindle cell types, and also in nevus cells.
Conclusions:
- MITF is a highly specific and sensitive marker, demonstrating strong expression in malignant melanoma, including challenging subtypes.
- MITF shows significant promise as a reliable immunomarker for the diagnosis and differential diagnosis of malignant melanoma.
- While S100 protein and HMB-45 have diagnostic value, MITF emerges as a superior marker for MM identification.

