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.
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.
Zavala-Pompa
A
A
Department of Pathology, Hospital de Especialidades #25, Instituto Mexicano del Seguro Social, Monterrey, Mexico.
Folpe
A L
AL
Jimenez
R E
RE
Lim
S D
SD
Cohen
C
C
Eble
J N
JN
Amin
M B
MB
D000199:Actins / Q000032:analysis; D018207:Angiomyolipoma / Q000737:chemistry*; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000737:chemistry*; D058950:Melanoma-Specific Antigens; D051739:Microphthalmia-Associated Transcription Factor; D014442:Monophenol Monooxygenase / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D012680:Sensitivity and Specificity; D014157:Transcription Factors
D000199:Actins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C072011:MAGEA1 protein, human; C497234:MITF protein, human; D058950:Melanoma-Specific Antigens; D051739:Microphthalmia-Associated Transcription Factor; D009363:Neoplasm Proteins; D014157:Transcription Factors; D014442:Monophenol Monooxygenase