Summary
To determine the characteristics of metaplastic changes of the nasal respiratory epithelium, the distribution of individual cytokeratins (CKs) was studied immunohistochemically and by two-dimensional gel electrophoresis. The authors define four types of changes of the normal pseudostratified columnar epithelium: (1) transitional pseudostratified epithelium (first unusual CK.: no. 13); (2) stratified columnar epithelium (increased expression of CKs 4 and 13; CKs 7, 8, 18 and 19 reduced); (3) stratified squamous epithelium, non-keratinized (appearance of CK 16); and (4) stratified squamous epithelium, keratinized (expression of CKs 1 and 10, variable CK5 and 14 patterns in basal cells). These phenotypes were found simultaneously within single specimens, resulting in apparent overall variability in the immunohistochemical staining patterns. Spatially, changes in CK expression towards “normal” parts were not abrupt but rather gradual. Biochemical data confirmed the immunohistochemical findings and added CK 6 to the pattern of altered nasal mucosa. The findings of this study suggest a stem cell metaplasia in the nasal epithelium which is based on its inherent bimodal developmental programme. A gradual loss of normal respiratory epithelial differentiation, as seen by the loss of CKs 7, 8, and 18, was paralleled by the appearance of squamous epithelial type CKs, e.g. the expression of CKs 1, 10 and 13. Basal cell types CKs 5, 14, 17 and 19 were maintained during this process. Implications of these results for general concepts of CK expression in the metaplastic process are discussed.
Similar content being viewed by others
References
Achtstätter T, Hatzfeld M, Quinlan RA, Parmelee DC, Franke WW (1986) Separation of cytokeratin polypeptides by gel electrophoretic and Chromatographic techniques and their identification by immunoblotting. Methods Enzymol 134:355–371
Bartek J, Durban EM, Hallowes RC, Taylor-Papadimitriou J (1985) A subclass of luminal cells in the human mammary gland defined by monoclonal antibodies to cytokeratins. J Cell Sci 75:1–17
Boenig H (1971) Leitfaden der Entwicklungsgeschichte des Menschen. Thieme, Leipzig, p 159
Boysen M (1985) Histopathology of the nasal mucosa in furniture workers. Rhinology 23:109–111
Boysen M, Reith A (1983) Discrimination of various epithelia by simple morphometric evaluation of the basal cell layer. Virchows Arch [B] 42:173–184.
Boysen M, Morton PF, Pilström L, Solberg LA, Torp T (1982) A simple and efficient method for objective discrimination between pseudostratified, metaplastic and dysplastic nasal epithelium. J Microsc 130:99–106
Boysen M, Voss R, Solberg LA (1986) The nasal mucosa in softwood exposed furniture workers. Acta Otolaryngol (Stockh) 101:501–50
Broers JL, Leij L, Klein-Rot M, Haar A, Lane EB, Leigh IM, Wafenaar SS, Vooijs GP, Ramaekers FCS (1989) Expression of intermediate filament proteins in fetal and adult human lung tissues. Differentiation 40:119–128
Carson JL, Collier AM, Knowles MR, Boucher RC, Rose JG (1981) Morphometric aspects of ciliary distribution and ciliogenesis in human nasal epithelium. Proc Natl Acad Sci USA 78:6996–6999
Carson JL, Collier AM, Hu SS (1985) Aquired ciliary defects in nasal epithelium of children with acute viral upper respiratory infections. N Engl J Med 312:463–46
Chopra DP (1982) Squamous metaplasia in organ cultures of vitamin A-deficient hamster trachea: cytokinetic and ultrastructural alteration. J Natl Cancer Inst 69:895–905
Cintorino MTDVM, Bugnoli M, Petracca R, Leoncini P (1988) Cytokeratin pattern in normal and pathological bladder urothelium: immunohistochemical investigation using monoclonal antibodies. J Urol 139:428–432
Cooper D, Schermer A, Sun T-T (1985) Classification of human epithelia and their neoplasms using monoclonal antibodies to keratins: strategies, applications, and limitations. Lab Invest 52:243–256
Evans MJ, Shami SG, Cabral-Anderson LJ, Dekker NP (1986) Role of nonciliated cell in renewal of the bronchial epithelium of rats exposed to NO2. Am J Pathol 123:126–133
Franke WW, Schiller DL, Moll R, Winter S, Schmidt E, Engelbrecht J, Denk H, Krepler R, Platzer B (1981) Diversity of cytokeratins. Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol 153:933–959
Fukuda Y, Takemura T, Ferrans VJ (1989) Evolution of metaplastic squamous cells of alveolar walls in pulmonary fibrosis produced by paraquat. An ultrastructural and immunohistochemical study. Virchows Arch [B] 58:27–43
Goertchen R, Kasper M, Stosiek P (1990) Das mucourotheliale Karzinom der Harnblase. Pathologe 11:166–170
Guelstein VI, Tchypysheva TA, Ermilova VD, Litvinova LV, Troyanovsky SM (1988) Monoclonal antibody mapping of keratins 8 and 17 and of vimentin in normal human mammary gland, benign tumors, dysplasias and breast cancer. Int J Cancer 42:147–253
Hajek M (1926) Pathologie und Therapie der entzündlichen Erkrankungen der Nebenhöhlen der Nase. Deuticke, Leipzig, p 98
Heid HW, Moll I, Franke WW (1988) Patterns of expression of trichocytic and epithelial cytokeratins in mammalian tissues. I. Human and bovine hair follicles. Differentiation 37:137–157
Hosemann W, Wigand ME (1985) Örtliche Unterschiede im Gewebebild der chronisch-hyperplastischen Nasennebenhöhlenschleimhaut. Pathology 33:311–315
Inayama Y, Hook GER, Brody AR, Cameron GS, Jetten AM, Gilmore LB, Gray T, Nettesheim P (1988) The differentiation potential of tracheal basal cells. Lab Invest 58:706–777
Karsten U, Widmaier R, Kunde D (1983) Monoclonal antibodies against antigens of the human mammary carcinoma cell line MCF-7. Arch Geschwulstforsch 53:529–536
Karsten U, Papsdorf G, Roloff G, Stolley P, Abel H, Walther I, Weiss H (1985) Monoclonal anti-cytokeratin antibody from a hybridoma clone generated by electrofusion. Eur J Cancer Clin Oncol 21:733–740
Kasper M (1991) Heterogeneity in the immunolocalization of cytokeratin specific monoclonal antibodies in the rat eye: evaluation of unusual epithelial tissue entities. Histochemistry 95:613–620
Kasper M, Stosiek P (1990) The expression of vimentin in epithelial cells from human nasal mucosa. Eur Arch Otorhinolaryngol 248:53–56
Kasper M, Stosiek P, Typlt H, Karsten U (1987) Histological evaluation of three new monoclonal anti cytokeratin antibodies. 1. Normal tissues. Eur J Cancer Clin Oncol 23:137–147
Klein-Szanto AJP, Boysen M, Reith A (1987) Keratin and involucrin in preneoplastic and neoplastic lesions. Arch Pathol Lab Med 111:1057–1061
Krstic RV (1984) Illustrated encyclopaedia of human histology. Springer, Berlin Heidelberg New York, p 348
Lane (1982) Monoclonal antibodies provide specific intramolecular markers for the study of epithelial tonofilament organization. J Cell Biol 92:665–673
Lane EB, Alexander CM (1990) Use of keratin antibodies in tumor diagnosis. Cancer Biol 1:165–169
Lane EB, Bartek J, Purkis PE, Leigh IM (1985) Keratin antigens in differentiating skin. Ann NY Acad Sci 455:241–258
Lauerova L, Kovarik J, Bartek J, Rejthar A, Vojtesek B (1988) Novel monoclonal antibodies defined epitope of human cytokeratin 18 molecule. Hybridoma 7:495–504
Leube RE, Rustad TJ (1991) Squamous cell metaplasia in the human lung: molecular characteristics of epithelial stratification. Virchows Arch [B] 61:227–253
Lindberg K, Rheinwald JG (1989) Suprabasal 40 kd keratin (K19) expression as an immunohistologic marker of premalignancy in oral epithelium. Am J Pathol 134:89–98
Lynch MH, O,Guin WM, Hardy C, Mak L, Sun T-T (1986) Acidic and basic hair/nail (“hard”) keratins. Their co-localization in upper cortical and cuticle cells of human hair follicle and their relationship to “soft” keratins. J Cell Biol 103:2593–2606
Moll R (1987) Epithelial tumor markers: cytokeratins and tissue polypeptide antigen. In: Seifert G (ed) Morphological tumor markers. Springer, Berlin Heidelberg New York, pp 71–102
Moll R (1988) Differenzierungsprogramme des Epithels und ihre Änderungen. Verh Dtsch Ges Pathol 72:102–114
Moll R (1992) Cytokeratine als Differenzierungsmarker: Expressionsprofile von Epithelien und epithelialen Tumoren. In: Seifert G (ed) Veröffentlichungen aus der Pathologie. Fischer, Stuttgart (in press)
Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The catalogue of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24
Moll R, Schiller D, Franke WW (1990) Identification of protein IT of the intestinal cytoskeleton as a novel type I cytokeratin with unusual properties and expression patterns. J Cell Biol 111:567–580
Morgan PR, Leigh JM, Purkis PE, Gardner JD, Muijen GNP van, Lane EB (1987) Site variation in keratin expression in human oral epithelia. Epithelia 13:31–43
Mossmann BT, Craighead JE (1975) Long-term maintenance of differentiated respiratory epithelium in organ culture. Proc Soc Exp Biol Med 149:227–233
Niimi T, Imaizumi M, Abe T, Haimoto H, Nagura H (1987) Immunohistochemical characteristics of proliferative and metaplastic lesions in bronchial mucosa. Am J Clin Pathol 8 8:545–551
Osborn M, Weber K (1983) Tumor diagnosis by intermediate filament typing: a novel tool for surgical pathology. Lab Invest 48:372–388
Purkis PE, Steel JB, Mackenzie IC, Nathrath WBJ, Leigh IM, Lane EB (1990) Antibody markers of basal cells in complex epithelia. J Cell Sci 97:39–50
Ramaekers FCS, Moesker O, Huysmans A, Schaat G, Westerhof G, Wagenaar SS, Herman CJ, Vooijs GP (1985) Intermediate filament proteins in the study of tumor heterogeneity: an indepth study of tumors of the urinary and respiratory tracts. Ann NY Acad Sci 455:614–634
Ramaeckers FCS, Huysmans A, Schaart G, Mosker O, Vooijs P (1987) Tissue distribution of keratin 7 as monitored by a monoclonal antibody. Exp Cell Res 170:235–249
Reid C, Jones R (1979) Bronchial mucosal cells. Fed Proc 38:191–196
Rhodin JA (1975) Atlas of histology. Oxford University Press, New York, p 352
Rossmann CM, Lee RM, Forrest JB, Newhouse MT (1984) Nasal ciliary ultrastructure and function in patients with primary ciliary dyskinesia compared with that in normal subjects and in subjects with various respiratory diseases. Am Rev Respir Dis 129:161–167
Rutten AA, Bruyntjes JP, Ramaekers FCS (1988) Effect of cigarette smoke condensate and vimentin A depletion in keratin expression patterns in cultured hamster tracheal epithelium. Virchows Arch [B] 56:111–117
Schaafsma HE, Ramaekers FCS, Muijen GNP van, Lane EB, Leigh IM, Robben H, Huijsmans A, Ooms ECM, Ruiter DJ (1990) Distribution of cytokeratin polypeptides in human transitional cell carcinomas, with special emphasis on changing expression patterns during tumor progression. Am J Pathol 136:329–343
Sigler RE, Newkirk C, McDowell EM (1988) Histogenesis and morphogenesis of epidermoid metaplasioa in hamster tracheal organ expiant culture. Virchows Arch [B] 55:47–55
Smedts F, Ramaekers FCS, Robben H, Pruszcynski M, Muijen GNP van, Lane EB, Leigh I, Vooijs P (1990) Changing patterns of keratin expression during progression of cervical intraepithelial neoplasia. Am J Pathol 136:657–668
Stosiek P, Kasper M (1990) Neoexpression von Cytokeratin 7 bei der chronisch-atrophischen Gastritis mit perniziöser Anämie. Pathologe 11:14–17
Stosiek P, Kasper M, Karsten U (1990) Expression of cytokeratins 8 and 18 in human Sertoli cells of immature and atrophic seminiferous tubule. Differentiation 43:66–70
Sun T-T, Eichner R, Schemer A, Cooper D, Nelson WG, Weiss RA (1984) Classification, expression and possible mechanisms of evaluation of mammalian epithelial keratins: an unifying model. In: Sun (ed.) The transformed phenotype, cancer cell, vol 1. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp 169–176
Trump BF, McDowell EM, Glavin F, Barett LA, Becci PJ, Schüsel W (1978) The respiratory epithelium. III. Histogenesis of epidermoid metaplasia and carcinoma in situ in the human. J Natl Cancer Inst 61:563–575
Van Muijen GNP, Ruiter DJ, Franke WW, Achtstätter T, Haasnoot WHB, Poneck M, Warnaar SO (1986) Cell type heterogeneity of cytokeratin expression in complex epithelia and carcinomas as demontrated by monoclonal antibodies specific for cytokeratins nos 4 and 13. Exp Cell Res 162:97–113
Virchow R (1871) Die Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebelehre, 4th edn. Hirschwald, Berlin, pp 364–365
Wang NS, Ying WL (1977) The pattern of goblet cell hyperplasia in human airways. Hum Pathol 8:301–311
Weiss RA, Eichner R, Sun T-T (1984) Monoclonal antibody analysis of keratin expression in epidermal disease: a 48-kD and a 56-kD keratin as molecular markers for hyperproliferative keratinocytes. J Cell Biol 98:1397–1406
WHO (1978) International histological classification of tumors, No. 19. WHO, Geneva
Zuckerkandl E (1892) Normale und pathologische Anatomie der Nasennebenhöhle und ihrer pneumatischen Anhänge. Braunmüller, Vienna, p 77
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stosiek, P., Kasper, M. & Moll, R. Changes in cytokeratin expression accompany squamous metaplasia of the human respiratory epithelium. Vichows Archiv A Pathol Anat 421, 133–141 (1992). https://doi.org/10.1007/BF01607046
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01607046