Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1990 Feb;136(2):329–343.

Distribution of cytokeratin polypeptides in human transitional cell carcinomas, with special emphasis on changing expression patterns during tumor progression.

H E Schaafsma 1, F C Ramaekers 1, G N van Muijen 1, E B Lane 1, I M Leigh 1, H Robben 1, A Huijsmans 1, E C Ooms 1, D J Ruiter 1
PMCID: PMC1877402  PMID: 1689541

Abstract

The expression of cytokeratin (CK) polypeptides was studied in 59 transitional cell carcinomas (TCC) of the urinary tract of different grade and stage. Using a panel of 14 polypeptide-specific monoclonal CK-antibodies we identified immunohistochemically 8 different CKs separately, ie, CKs 4, 7, 8, 10, 13, 14, 18, and 19, while in immunoblotting studies CK5 expression was detected indirectly by using the antibody RCK102, recognizing CK5 + 8. In low-grade TCCs (G1-G2), the CK distribution was comparable to that in normal urothelium, however with a variable expression of CK13 in the different tumors and a uniform distribution of CK7. In higher-grade TCCs (G3), a decrease in CK13 expression was observed, particularly in the areas of muscle invasion. Furthermore, the appearance and increasing expression of CK14 (not present in normal urothelium or G1 TCCs) with higher grade and stage was striking. With tumor progression changes in epitope configurations of CK8 and CK18 were detected, as concluded from immunohistochemical assays with the panel of monoclonal antibodies for each of these two CKs. In extreme cases this resulted in differential staining patterns of the invasive and noninvasive components within one tumor. In 7 of 32 G3 TCCs, some of which showed areas with evident squamous differentiation, a decrease in the expression of CK7 and/or CK8 was seen. We conclude that tumor progression in TCCs is associated with discrete changes of CK expression, which can be detected using monoclonal antibodies.

Full text

PDF
329

Images in this article

332Figure 1
on p.332
333Figure 1
on p.333
334Figure 2
on p.334
339Figure 3
on p.339
340Figure 4
on p.340
341Figure 5
on p.341

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abel P. D., Hall R. R., Williams G. Should pT1 transitional cell cancers of the bladder still be classified as superficial? Br J Urol. 1988 Sep;62(3):235–239. doi: 10.1111/j.1464-410x.1988.tb04325.x. [DOI] [PubMed] [Google Scholar]
  2. Achtstätter T., Moll R., Moore B., Franke W. W. Cytokeratin polypeptide patterns of different epithelia of the human male urogenital tract: immunofluorescence and gel electrophoretic studies. J Histochem Cytochem. 1985 May;33(5):415–426. doi: 10.1177/33.5.2580881. [DOI] [PubMed] [Google Scholar]
  3. Anderström C., Johansson S., Nilsson S. The significance of lamina propria invasion on the prognosis of patients with bladder tumors. J Urol. 1980 Jul;124(1):23–26. doi: 10.1016/s0022-5347(17)55272-6. [DOI] [PubMed] [Google Scholar]
  4. Asamoto M., Fukushima S., Tatemoto Y., Yamada K., Fukui S., Mori M. Immunohistochemical expression of keratin proteins in urinary bladder carcinoma. Pathol Res Pract. 1989 Feb;184(2):194–201. doi: 10.1016/S0344-0338(89)80120-7. [DOI] [PubMed] [Google Scholar]
  5. Broers J. L., Carney D. N., Klein Rot M., Schaart G., Lane E. B., Vooijs G. P., Ramaekers F. C. Intermediate filament proteins in classic and variant types of small cell lung carcinoma cell lines: a biochemical and immunochemical analysis using a panel of monoclonal and polyclonal antibodies. J Cell Sci. 1986 Jul;83:37–60. doi: 10.1242/jcs.83.1.37. [DOI] [PubMed] [Google Scholar]
  6. Broers J. L., Ramaekers F. C., Rot M. K., Oostendorp T., Huysmans A., van Muijen G. N., Wagenaar S. S., Vooijs G. P. Cytokeratins in different types of human lung cancer as monitored by chain-specific monoclonal antibodies. Cancer Res. 1988 Jun 1;48(11):3221–3229. [PubMed] [Google Scholar]
  7. Cintorino M., Del Vecchio M. T., Bugnoli M., Petracca R., Leoncini P. Cytokeratin pattern in normal and pathological bladder urothelium: immunohistochemical investigation using monoclonal antibodies. J Urol. 1988 Feb;139(2):428–432. doi: 10.1016/s0022-5347(17)42449-9. [DOI] [PubMed] [Google Scholar]
  8. Feitz W. F., Beck H. L., Smeets A. W., Debruyne F. M., Vooijs G. P., Herman C. J., Ramaekers F. C. Tissue-specific markers in flow cytometry of urological cancers: cytokeratins in bladder carcinoma. Int J Cancer. 1985 Sep 15;36(3):349–356. [PubMed] [Google Scholar]
  9. Fukushima S., Ito N., el-Bolkainy M. N., Tawfik H. N., Tatemoto Y., Mori M. Immunohistochemical observations of keratins, involucrin, and epithelial membrane antigen in urinary bladder carcinomas from patients infected with Schistosoma haematobium. Virchows Arch A Pathol Anat Histopathol. 1987;411(2):103–115. doi: 10.1007/BF00712734. [DOI] [PubMed] [Google Scholar]
  10. Guelstein V. I., Tchypysheva T. A., Ermilova V. D., Litvinova L. V., Troyanovsky S. M., Bannikov G. A. 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. 1988 Aug 15;42(2):147–153. doi: 10.1002/ijc.2910420202. [DOI] [PubMed] [Google Scholar]
  11. Jarasch E. D., Nagle R. B., Kaufmann M., Maurer C., Böcker W. J. Differential diagnosis of benign epithelial proliferations and carcinomas of the breast using antibodies to cytokeratins. Hum Pathol. 1988 Mar;19(3):276–289. doi: 10.1016/s0046-8177(88)80520-3. [DOI] [PubMed] [Google Scholar]
  12. Jordan A. M., Weingarten J., Murphy W. M. Transitional cell neoplasms of the urinary bladder. Can biologic potential be predicted from histologic grading? Cancer. 1987 Dec 1;60(11):2766–2774. doi: 10.1002/1097-0142(19871201)60:11<2766::aid-cncr2820601129>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  13. Kern W. H. The grade and pathologic stage of bladder cancer. Cancer. 1984 Mar 1;53(5):1185–1189. doi: 10.1002/1097-0142(19840301)53:5<1185::aid-cncr2820530526>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  14. Lane E. B., Bártek J., Purkis P. E., Leigh I. M. Keratin antigens in differentiating skin. Ann N Y Acad Sci. 1985;455:241–258. doi: 10.1111/j.1749-6632.1985.tb50415.x. [DOI] [PubMed] [Google Scholar]
  15. Lane E. B. Monoclonal antibodies provide specific intramolecular markers for the study of epithelial tonofilament organization. J Cell Biol. 1982 Mar;92(3):665–673. doi: 10.1083/jcb.92.3.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lifschitz-Mercer B., Czernobilsky B., Shezen E., Dgani R., Leitner O., Geiger B. Selective expression of cytokeratin polypeptides in various epithelia of human Brenner tumor. Hum Pathol. 1988 Jun;19(6):640–650. doi: 10.1016/s0046-8177(88)80169-2. [DOI] [PubMed] [Google Scholar]
  17. Lutzeyer W., Rübben H., Dahm H. Prognostic parameters in superficial bladder cancer: an analysis of 315 cases. J Urol. 1982 Feb;127(2):250–252. doi: 10.1016/s0022-5347(17)53725-8. [DOI] [PubMed] [Google Scholar]
  18. Moll R., Achtstätter T., Becht E., Balcarova-Ständer J., Ittensohn M., Franke W. W. Cytokeratins in normal and malignant transitional epithelium. Maintenance of expression of urothelial differentiation features in transitional cell carcinomas and bladder carcinoma cell culture lines. Am J Pathol. 1988 Jul;132(1):123–144. [PMC free article] [PubMed] [Google Scholar]
  19. Moll R., Franke W. W., Schiller D. L., Geiger B., Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. doi: 10.1016/0092-8674(82)90400-7. [DOI] [PubMed] [Google Scholar]
  20. Ooms E. C., Anderson W. A., Alons C. L., Boon M. E., Veldhuizen R. W. Analysis of the performance of pathologists in the grading of bladder tumors. Hum Pathol. 1983 Feb;14(2):140–143. doi: 10.1016/s0046-8177(83)80242-1. [DOI] [PubMed] [Google Scholar]
  21. Ooms E. C., Blok A. P., Veldhuizen R. W. The reproducibility of a quantitative grading system of bladder tumours. Histopathology. 1985 May;9(5):501–509. doi: 10.1111/j.1365-2559.1985.tb02831.x. [DOI] [PubMed] [Google Scholar]
  22. Quinlan R. A., Schiller D. L., Hatzfeld M., Achtstätter T., Moll R., Jorcano J. L., Magin T. M., Franke W. W. Patterns of expression and organization of cytokeratin intermediate filaments. Ann N Y Acad Sci. 1985;455:282–306. doi: 10.1111/j.1749-6632.1985.tb50418.x. [DOI] [PubMed] [Google Scholar]
  23. Ramaekers F., Huysmans A., Moesker O., Kant A., Jap P., Herman C., Vooijs P. Monoclonal antibody to keratin filaments, specific for glandular epithelia and their tumors. Use in surgical pathology. Lab Invest. 1983 Sep;49(3):353–361. [PubMed] [Google Scholar]
  24. Ramaekers F., Huysmans A., Moesker O., Schaart G., Herman C., Vooijs P. Cytokeratin expression during neoplastic progression of human transitional cell carcinomas as detected by a monoclonal and a polyclonal antibody. Lab Invest. 1985 Jan;52(1):31–38. [PubMed] [Google Scholar]
  25. Ramaekers F., Huysmans A., Schaart G., Moesker O., Vooijs P. Tissue distribution of keratin 7 as monitored by a monoclonal antibody. Exp Cell Res. 1987 May;170(1):235–249. doi: 10.1016/0014-4827(87)90133-9. [DOI] [PubMed] [Google Scholar]
  26. Schaafsma H. E., Ramaekers F. C., van Muijen G. N., Ooms E. C., Ruiter D. J. Distribution of cytokeratin polypeptides in epithelia of the adult human urinary tract. Histochemistry. 1989;91(2):151–159. doi: 10.1007/BF00492389. [DOI] [PubMed] [Google Scholar]
  27. Sun T. T., Tseng S. C., Huang A. J., Cooper D., Schermer A., Lynch M. H., Weiss R., Eichner R. Monoclonal antibody studies of mammalian epithelial keratins: a review. Ann N Y Acad Sci. 1985;455:307–329. doi: 10.1111/j.1749-6632.1985.tb50419.x. [DOI] [PubMed] [Google Scholar]
  28. Tseng S. C., Jarvinen M. J., Nelson W. G., Huang J. W., Woodcock-Mitchell J., Sun T. T. Correlation of specific keratins with different types of epithelial differentiation: monoclonal antibody studies. Cell. 1982 Sep;30(2):361–372. doi: 10.1016/0092-8674(82)90234-3. [DOI] [PubMed] [Google Scholar]
  29. Tungekar M. F., Gatter K. C., Al-Adnani M. S. Immunohistochemistry of cytokeratin proteins in squamous and transitional cell lesions of the urinary tract. J Clin Pathol. 1988 Dec;41(12):1288–1296. doi: 10.1136/jcp.41.12.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. van Muijen G. N., Ruiter D. J., Franke W. W., Achtstätter T., Haasnoot W. H., Ponec M., Warnaar S. O. Cell type heterogeneity of cytokeratin expression in complex epithelia and carcinomas as demonstrated by monoclonal antibodies specific for cytokeratins nos. 4 and 13. Exp Cell Res. 1986 Jan;162(1):97–113. doi: 10.1016/0014-4827(86)90429-5. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES