Immunohistochemical study of microphthalmia transcription factor and tyrosinase in angiomyolipoma of the kidney, renal cell carcinoma, and renal and retroperitoneal sarcomas: comparative evaluation with traditional diagnostic markers.

Abstract

Angiomyolipoma has a unique immunophenotype with co-expression of muscle-specific actin and melanocytic markers such as HMB-45 and Melan-A. The most recently developed melanocytic markers, microphthalmia transcription factor and tyrosinase, have not been studied in the diagnosis of angiomyolipoma. We tested 29 renal angiomyolipomas (21 classic histology, 4 epithelioid variants, 2 lipomatous variants, and 2 leiomyomatous variants) with an immunohistochemical panel, including microphthalmia transcription factor, tyrosinase, HMB-45, Melan-A, and muscle-specific actin. Results were compared with 15 renal cell carcinomas (9 conventional types, 6 with sarcomatoid change), 2 leiomyosarcomas, 5 liposarcomas, and 1 unclassified high-grade sarcoma. Microphthalmia transcription factor expression was seen in 22 of 29 angiomyolipomas, one renal cell carcinoma, and one well-differentiated liposarcoma (that is, 2 of 23 non-angiomyolipomas; sensitivity 75%, specificity 91%). Tyrosinase expression was seen in 4 of 29 angiomyolipomas and 0 of 23 non-angiomyolipomas (sensitivity 14%, specificity 100%). HMB-45 was positive in 24 of 29 angiomyolipomas and 0 of 23 non-angiomyolipomas (sensitivity 83%, specificity 100%). Melan-A was expressed by 25 of 29 angiomyolipomas and 0 of 23 non-angiomyolipomas (sensitivity 86%, specificity 100%). Muscle-specific actin was expressed by 29 of 29 angiomyolipomas and 2 of 23 non-angiomyolipomas (both leiomyosarcomas; sensitivity 100%, specificity 91% [100% excluding leiomyosarcomas]). Microphthalmia transcription factor showed the most widespread staining in angiomyolipoma (50% of cases staining more than half of the tumor cells) followed by Melan-A (24% of cases staining more than 50%). Only three cases showed positivity for all four melanocytic markers, while in one case each only microphthalmia transcription factor and Melan-A were positive. We conclude that microphthalmia transcription factor, but not tyrosinase immunostaining, has a sensitivity and specificity that rivals those of the established markers, HMB-45 and Melan-A, in the diagnosis of angiomyolipoma. Our data supports the use of a panel in difficult cases that includes antibodies to microphthalmia transcription factor, either Melan-A or HMB-45, and muscle-specific actin to provide the best mix of high sensitivity, high specificity, nuclear and cytoplasmic immunolocalization, and widespread staining of cells within a given tumor.

• Authors: A Zavala-Pompa, A L Folpe, R E Jimenez, S D Lim, C Cohen, J N Eble, M B Amin
• Journal: The American journal of surgical pathology (Am J Surg Pathol) Vol. 25 Issue 1 Pg. 65-70 (Jan 2001) ISSN: 0147-5185 [Print] United States
• PMID: 11145253 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Actins
• Antigens, Neoplasm
• Biomarkers, Tumor
• DNA-Binding Proteins
• MAGEA1 protein, human
• MITF protein, human
• Melanoma-Specific Antigens
• Microphthalmia-Associated Transcription Factor
• Neoplasm Proteins
• Transcription Factors
• Monophenol Monooxygenase

Topics

• Actins (analysis)
• Angiomyolipoma (chemistry)
• Antigens, Neoplasm
• Biomarkers, Tumor (analysis)
• DNA-Binding Proteins (analysis)
• Humans
• Immunohistochemistry
• Kidney Neoplasms (chemistry)
• Melanoma-Specific Antigens
• Microphthalmia-Associated Transcription Factor
• Monophenol Monooxygenase (analysis)
• Neoplasm Proteins (analysis)
• Sensitivity and Specificity
• Transcription Factors