ASMA

(Alpha-Smooth Muscle Actin)
Characteristics
Actins comprise a group of cytoplasmic microfilaments, 6 nm in diameter, 42 kDa. By electrophoresis they can be separated into six different isotypes. The four isotypes of alpha actins are found in muscle cells, while beta and gamma actins are more ubiquitous. Alpha-smooth muscle actin (ASMA) is identified in smooth muscle cells, myofibroblasts, hepatic perisinusoidal cells, pericytes, and myoepithelial cells. Myofibroblasts may appear in association with many reactive processes in various tissues and usually accompanies malignant neoplasms.
Neoplasms
ASMA is detected in virtually all cases of leiomyomatous tumours, e.g., glomus tumour and leiomyosarcoma, in myofibroblastic tumours, e.g., fibromatoses, myofibosarcoma, myoepithelial tumours, some vascular tumours, e.g., angiomyxoma, haemangiosarcoma, and Kaposi sarcoma, in other mesenchymal tumours such as angioleiomyolipoma, synovial sarcoma, and angiomatoid malignant fibrous histiocytoma, and in ovarian granulosa-stromal tumours. Gastrointestinal stromal tumour (GIST) stains in about 50% of the cases, usually in a heterogeneous pattern. A number of other mesenchymal tumours may reveal a component of myofibroblastic cells, which hampers the use of ASMA in tumour differentiation. In few cases, aberrant ASMA expression has also been described in various tumours such as spindle cell and metaplastic carcinoma, epithelioid and desmoplastic malignant melanoma, alveolar soft part sarcoma, malignant mesothelioma, desmoplastic small round cell tumour, and osteogenic sarcoma. With the exception of the above mentioned variants, ASMA is rarely detected in carcinomas and melanomas. ASMA is not detected in neuronal, glial or schwannian tumours.
Application
In an appropriate panel, ASMA is used as a discriminator of smooth muscle cell differentiation in the classification of spindled and pleomorphic tumours. Together with cytokeratin, ASMA can be used for the identification of granulosa-stromal tumours and myoepithelial tumours. ASMA has been used for the distinction between benign proliferative breast lesions (in which the myoeithelial cell layer is preserved) and neoplastic proliferation (in which the myoepithelial cells are destroyed). However, antibodies to p63 and cytokeratin 5 are more sensitive and specific.
Controls
Appendix and liver are recommendable positive and negative tissue controls for ASMA. Virtually all smooth muscle cells in vessels, appendiceal muscularis mucosae and lamina propria must show a moderate to strong cytoplasmic staining reaction, while the majority of the perisinusoidal cells (hepatic stellate cells) in the liver must show an at least weak to moderate, distinct staining reaction. No staining reaction should be seen in appendiceal columnar epithelial cells, lymphocytes or liver cells.
Selected references
Hasegawa T, Seki K, Ono K, Hirohashi S. Angiomatoid (malignant) fibrous histiocytoma: a peculiar low-grade tumor showing immunophenotypic heterogeneity and ultrastructural variations. Pathol Int. 2000 Sep;50(9):731-8. Hiruta N, Kameda N, Tokudome T, Tsuchiya K, Nonaka H, Hatori T, Akima M, Miura M. Malignant glomus tumor: a case report and review of the literature. Am J Surg Pathol. 1997 Sep;21(9):1096-103. Review. Hishida T, Hasegawa T, Asamura H, Kusumoto M, Maeshima A, Matsuno Y, Suzuki K, Kondo H, Tsuchiya R. Malignant glomus tumor of the lung. Pathol Int. 2003 Sep;53(9):632-6. Kutzner H, Mentzel T, Kaddu S, Soares LM, Sangueza OP, Requena L. Cutaneous myoepithelioma: an under-recognized cutaneous neoplasm composed of myoepithelial cells. Am J Surg Pathol. 2001 Mar;25(3):348-55. L'Hostis H, Deminiere C, Ferriere JM, Coindre JM. Renal angiomyolipoma: a clinicopathologic, immunohistochemical, and follow-up study of 46 cases. Am J Surg Pathol. 1999 Sep;23(9):1011-20. Lukinmaa PL, Hietanen J, Warfvinge G, Sane J, Tuominen S, Henriksson V, Larsson A. Solitary fibrous tumour of the oral cavity: clinicopathological and immunohistochemical characterization of three cases. J Oral Pathol Med. 2000 Apr;29(4):186-92. Meis-Kindblom JM, Kindblom LG. Angiosarcoma of soft tissue: a study of 80 cases. Am J Surg Pathol. 1998 Jun;22(6):683-97. Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J. Gastrointestinal stromal tumors and leiomyosarcomas in the colon: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases. Am J Surg Pathol. 2000 Oct;24(10):1339-52. Nonomura A, Mizukami Y, Takayanagi N, Masuda S, Ishii K, Tashiro K, Mizoguchi Y. Immunohistochemical study of hepatic angiomyolipoma. Pathol Int. 1996 Jan;46(1):24-32. Oda Y, Miyajima K, Kawaguchi K, Tamiya S, Oshiro Y, Hachitanda Y, Oya M, Iwamoto Y, Tsuneyoshi M. Pleomorphic leiomyosarcoma: clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and malignant fibrous histiocytoma. Am J Surg Pathol. 2001 Aug;25(8):1030-8. Ordonez NG. Desmoplastic small round cell tumor: II: an ultrastructural and immunohistochemical study with emphasis on new immunohistochemical markers. Am J Surg Pathol. 1998 Nov;22(11):1314-27. Review. Shidham VB, Chivukula M, Gupta D, Rao RN, Komorowski R. Immunohistochemical comparison of gastrointestinal stromal tumor and solitary fibrous tumor. Arch Pathol Lab Med. 2002 Oct;126(10):1189-92. Tsuji Y, Okada K, Fukuoka M, Watanabe Y, Ataka K, Minami R, Hanioka K, Tachibana S, Saito H, Sasada A, Okita Y. Hepatocellular carcinoma with a sarcomatous appearance: report of a case. Surg Today. 2001;31(8):735-9. Winnepenninckx V, De Vos R, Stas M, van den Oord JJ. New phenotypical and ultrastructural findings in spindle cell (desmoplastic/neurotropic) melanoma. Appl Immunohistochem Mol Morphol. 2003 Dec;11(4):319-25.
02.12.09 - MV/LE