Complex and Differential Cytokeratin Profiles in Thymomas and Correlation with Normal Thymus
Cytokeratins (CKs) are characterized by highly diverse expression patterns and thus serve as potent epithelial differentiation markers. We have studied 31 cases of thymomas (12 cortical, 2 predominantly cortical, 5 mixed, and 9 medullary type thymomas as well as 3 well-differentiated thymic carcinomas) and, for comparison, 15 normal thymi, for the presence of different CK polypeptides. Immunohistochemistry was performed on cryostat sections using the indirect immunoperoxidase method.
In normal medullary epithelial cells, all 16 CKs studied were detected with variable frequencies. Cortical epithelial cells showed less complex patterns, mainly composed of the simple-epithelial CKs 8 and 19 and the stratified-epithelial CK 14. In the subcapsular epithelium, CKs 5, 14 and 19 were predominant.
Analyses of the thymomas revealed a broad spectrum of variably complex CK patterns which, although being fluid, allowed the definition of several quite distinct CK phenotypes. All thymomas co-expressed simple-epithelial (CKs 8, 18, 19) and stratified-epithelial (mainly CKs 5, 14, 15 and 17) CKs. Half of the cortical thymomas revealed a phenotype with predominance of CKs 5 and 15 while 5/9 medullary thymomas showed prevalence of CK 14. Focal expression of CK 6 was more typical of cortical thymomas. CKs 4, 7, 10, 13 and 20 were inconstantly and sparsely expressed, with enhancement of CKs 4, 7 and 13 in cystic structures. “Medullary differentiation” usually was accompanied by a shift towards enhanced stratified-epithelial CKs. Seven cases contained neurofilaments.
The data demonstrate partial correlations between particular CK patterns and the morphological subtypes of thymomas although there are no simple relations to the normal thymic zones. The possible biological significance of the different CK phenotypes needs to be substantiated with larger series.
KeywordsThymic Carcinoma Thymic Epithelial Cell Thymic Epithelial Tumor Cytokeratin Expression Normal Thymus
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- Heid HW, Moll I, Franke WW: Patterns of expression of trichocytic and epithelial cytokera-tins in mammalian tissues: II. Concomitant and exclusive synthesis of trichocytic and epithe-lial cytokeratins in diverse human and bovine tissues (hair follicle, nail bed and matrix, lingual papilla, thymic reticulum). Differentiation 37:215–230 (1988).PubMedCrossRefGoogle Scholar
- Kirchner T, Müller-Hermelink HK: New approaches to the diagnosis of thymic epithelial tumors. In: Progress in Surgical Pathology, Vol. 10. Field and Wood, Philadelphia, pp. 167-189 (1989)Google Scholar
- Marx A, Kirchner T, Greiner A, Schalke B, Müller-Hermelink HK: Neurofilament epitope expression in thymic epithelial tumors and anti-axonal autoantibodies in myasthenia gravis: A model for autoimmunity by abnormal T cell selection. Verh Dtsch Ges Path 76:256–261 (1992).Google Scholar
- Moll R: Cytokeratins as markers of differentiation: Expression profiles in epithelia and epithelial tumors. Progress in Pathology, vol. 142. Gustav Fischer Verlag, Stuttgart, Jena, New York, pp 1-197 (1993)Google Scholar
- Ochs BA, Hofmann W, Franke WW, Otto HF: Immunhistochemische und biochemische Unter-suchung der Cytokeratine im normalen menschlichen Thymusepithel und in Thymomen. Verh. Dtsch. Ges. Path 70:591 (1986).Google Scholar
- Schaafsma HE, Ramaekers FCS: Cytokeratin subtyping in normal and neoplastic epithelium: Basic principles and diagnostic applications. In: Rosen PP, Fechner RE, eds. Pathology Annual, part1, vol. 29. Appleton & Lange, Norwalk. pp 21–62 (1994).Google Scholar
- Viac J, Schmitt D, Staquet MJ, Thivolet J: Epidermis-thymus antigenic relations with special reference to Hassall’s corpuscles. Thymus 1:319–328 (1980).Google Scholar