Skip to main content
Log in

Expression of adhesion molecules and cytokeratin 20 in merkel cell carcinomas

  • Clinical Research
  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. MCCs often show characteristic paranuclear dot-like immunopositivity for cytokeratin 20 (CK20), a globular aggregation of CK20 intermediate filaments. These aggregates typically form rhabdoid features and fibrous bodies and may be associated with a down-regulation in adhesion molecules (AMs). To date, the relationship between the expression of AMs and CK20 and clinicopathological findings in MCC has not been well examined. In this immunohistochemical study, we assessed the expression of AMs, CK20, and chromogranin A (CgA) on MCCs in 8 men and 23 women with this disease, and also characterized their clinicopathological features. This study is the largest of its kind that has been undertaken to date in Japanese patients.

Compared to normal tissue, E-cadherin and α- and β-catenins showed reduced membranous expression in 95.7%, 46.7%, and 45.2% of MCCs, respectively. Nuclear E-cadherin localization was seen in four tumors, all of which predominantly showed a CK20 dot pattern. However, there was no significant relationship between the membranous expression of AMs and a CK20 dot pattern. E-cadherin expression was significantly lower in tumors of ≥2 cm, and tumors negative for E-cadherin more frequently developed outside of the head and neck than within those regions. CgA was more intensely expressed in tumors with uniform nuclei and a dense lymphocytic infiltrate than in those that showed pleomorphisms and that had few, if any, infiltrating lymphocytes.

These findings suggest that MCCs have a reduced expression of AMs and that down-regulation of E-cadherin expression may correlate with increased tumor aggressiveness. The fact that no significant relationship was demonstrable between the membranous expression of AMs and the CK20 expression pattern suggests that the mechanism of aggregation of intermediate filaments may be different in different types of tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Toker C. Trabecular carcinoma of the skin. Arch Dermatol 105:107–110, 1972.

    Article  PubMed  CAS  Google Scholar 

  2. Tang CK, Toker C. Trabecular carcinoma of the skin: further clinicopathologic and ultrastructural study. Mt Sinai J Med 46:516–523, 1979.

    PubMed  CAS  Google Scholar 

  3. Wick MR, Goellner JR, Scheithauer BW, Thomas JR 3rd, Sanchez NP, Schroeter AL. Primary neuroendocrine carcinomas of the skin (Merkel cell tumors). A clinical, histologic, and ultrastructural study of thirteen cases. Am J Clin Pathol 79:6–13, 1983.

    PubMed  CAS  Google Scholar 

  4. Cooper L, Debono R, Alsanjari N, Al-Nafussi A. Merkel cell tumour with leiomyosarcomatous differentiation. Histopathology 36:540–543, 2000.

    Article  PubMed  CAS  Google Scholar 

  5. Skelton HG, Smith KJ, Hitchcock CL, McCarthy WF, Lupton GP, Graham JH. Merkel cell carcinoma: analysis of clinical, histologic, and immunohistologic features of 132 cases with relation to survival. J Am Acad Dermatol 37(5 Pt 1):734–739, 1997.

    Article  PubMed  CAS  Google Scholar 

  6. Alvarez-Gago T, Bullon MM, Rivera F, Velasco A, Mayo A. Intermediate filament aggregates in mitoses of primary cutaneous neuroendocrine (Merkel cell) carcinoma. Histopathology 28:349–355, 1996.

    Article  PubMed  CAS  Google Scholar 

  7. Scott MP, Helm KF. Cytokeratin 20: a marker for diagnosing Merkel cell carcinoma. Am J Dermatopathol 21:16–20, 1999.

    Article  PubMed  CAS  Google Scholar 

  8. Jensen K, Kohler S, Rouse RV. Cytokeratin staining in Merkel cell carcinoma: an immunohistochemical study of cytokeratins 5/6, 7, 17, and 20. Appl Immunohistochem Mol Morphol 8:310–315, 2000.

    Article  PubMed  CAS  Google Scholar 

  9. Horvath E, Kovacs K. Morphogenesis and significance of fibrous bodies in human pituitary adenomas. Virchows Arch B Cell Pathol 27:69–78, 1978.

    PubMed  CAS  Google Scholar 

  10. Perez-Montiel MD, Frankel WL, Suster S. Neuroendocrine carcinomas of the pancreas with “Rhabdoid” features. Am J Surg Pathol 27:642–649, 2003.

    Article  PubMed  Google Scholar 

  11. Shimazaki H, Aida S, Sato M, Deguchi H, Ozeki Y, Tamai S. Lung carcinoma with rhabdoid cells: a clinicopathological study and survival analysis of 14 cases. Histopathology 38:425–434, 2001.

    Article  PubMed  CAS  Google Scholar 

  12. Saito T, Oda Y, Itakura E, et al. Expression of intercellular adhesion molecules in epithelioid sarcoma and malignant rhabdoid tumor. Pathol Int 51:532–542, 2001.

    Article  PubMed  CAS  Google Scholar 

  13. Hirohashi S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol 153:333–339, 1998.

    PubMed  CAS  Google Scholar 

  14. Li CC, Xu B, Hirokawa M, et al. Alterations of E-cadherin, alpha-catenin and beta-catenin expression in neuroendocrine tumors of the gastrointestinal tract. Virchows Arch 440:145–154, 2002.

    Article  PubMed  CAS  Google Scholar 

  15. Berx G, Nollet F, van Roy F. Dysregulation of the E-cadherin/catenin complex by irreversible mutations in human carcinomas. Cell Adhes Commun 6:171–184, 1998.

    Article  PubMed  CAS  Google Scholar 

  16. Clavel CE, Nollet F, Berx G, et al. Expression of the E-cadherin-catenin complex in lung neuroendocrine tumours. J Pathol 194:20–26, 2001.

    Article  PubMed  CAS  Google Scholar 

  17. Nakopoulou L, Gakiopoulou-Givalou H, Karayiannakis AJ, et al. Abnormal alphacatenin expression in invasive breast cancer correlates with poor patient survival. Histopathology 40:536–546, 2002.

    Article  PubMed  CAS  Google Scholar 

  18. Reed RJ, Argenyi Z. Tumors of Neural Tissue. In: Elder D, ed. Lever’s histopathology of the skin. 8th ed. Philadelphia, PA: Lippincott-Raven, 1997; 1000–1002.

    Google Scholar 

  19. Han AC, Soler AP, Tang CK, Knudsen KA, Salazar H. Nuclear localization of E-cadherin expression in Merkel cell carcinoma. Arch Pathol Lab Med 124:1147–1151, 2000.

    PubMed  CAS  Google Scholar 

  20. Qian ZR, Li CC, Yamasaki H, et al. Role of E-cadherin, alpha-, beta-, and gammacatenins, and pl20 (cell adhesion molecules) in prolactinoma behavior. Mod Pathol 15:1357–1365, 2002.

    Article  PubMed  Google Scholar 

  21. Fei Q, Zhang H, Chen X, et al. Defected expression of E-cadherin in non-small cell lung cancer. Lung Cancer 37:147–152, 2002.

    Article  PubMed  Google Scholar 

  22. Wei Y, Van Nhieu JT, Prigent S, Srivatanakul P, Tiollais P, Buendia MA. Altered expression of E-cadherin in hepatocellular carcinoma: correlations with genetic alterations, betacatenin expression, and clinical features. Hepatology 36:692–701, 2002.

    Article  PubMed  CAS  Google Scholar 

  23. Horiguchi T, Sano T, Qian ZR, et al. Expression of cell adhesion molecules in chordomas: An immunohistochemical study of 16 cases. Acta Neuropathol (Berl) 107:91–96, 2003.

    Article  CAS  Google Scholar 

  24. Xu B, Sano T, Yoshimoto K, Yamada S. Downregulation of E-cadherin and its undercoat proteins in pituitary growth hormone cell adenomas with prominent fibrous bodies. Endocr Pathol 13:341–351, 2002.

    Article  PubMed  CAS  Google Scholar 

  25. Said JW, Vimadalal S, Nash G, et al. Immunoreactive neuron-specific enolase, bombesin, and chromogranin as markers for neuroendocrine lung tumors. Hum Pathol 16:236–240, 1985.

    Article  PubMed  CAS  Google Scholar 

  26. Okano K, Maeba T, Moroguchi A, et al. Lymphocytic infiltration surrounding liver metastases from colorectal cancer. J Surg Oncol 82:28–33, 2003.

    Article  PubMed  Google Scholar 

  27. Chan JK, Suster S, Wenig BM, Tsang WY, Chan JB, Lau AL. Cytokeratin 20 immunoreactivity distinguishes Merkel cell (primary cutaneous neuroendocrine) carcinomas and salivary gland small cell carcinomas from small cell carcinomas of various sites. Am J Surg Pathol 21:226–234, 1997.

    Article  PubMed  CAS  Google Scholar 

  28. Hall PA, d’Ardenne AJ, Butler MG, et al. Cytokeratin and laminin immunostaining in the diagnosis of cutaneous neuro-endocrine (Merkel cell) tumours. Histopathology 10:1179–1190, 1986.

    Article  PubMed  CAS  Google Scholar 

  29. Moll I, Kuhn C, Moll R. Cytokeratin 20 is a general marker of cutaneous Merkel cells while certain neuronal proteins are absent. J Invest Dermatol 104:910–915, 1995.

    Article  PubMed  CAS  Google Scholar 

  30. Wick MR. Immunohistology of neuroendocrine and neuroectodermal tumors. Semin Diagn Pathol. 17:194–203, 2000.

    PubMed  CAS  Google Scholar 

  31. Rosai J. Skin. In: Rosai J, ed. Ackerman’s surgical pathology. 8th ed. St. Louis, MO: Mosby, 1996; 166–168.

    Google Scholar 

  32. Baschinsky DY, Niemann TH, Eaton LA, Frankel WL. Malignant mixed Mullerian tumor with rhabdoid features: a report of two cases and a review of the literature. Gynecol Oncol 73:145–150, 1999.

    Article  PubMed  CAS  Google Scholar 

  33. Mazal PR, Czech T, Sedivy R, et al. Prognostic relevance of intracytoplasmic cytokeratin pattern, hormone expression profile, and cell proliferation in pituitary adenomas of acromegalic patients. Clin Neuropathol. 20:163–171, 2001.

    PubMed  CAS  Google Scholar 

  34. Sano T, Ohshima T, Yamada S. Expression of glycoprotein hormones and intracytoplasmic distribution of cytokeratin in growth hormone-producing pituitary adenomas. Pathol Res Pract 187:530–533, 1991.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Toshiaki Sano MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tanaka, Y., Sano, T., Qian, Z.R. et al. Expression of adhesion molecules and cytokeratin 20 in merkel cell carcinomas. Endocr Pathol 15, 117–129 (2004). https://doi.org/10.1385/EP:15:2:117

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/EP:15:2:117

Key Words

Navigation