Early B-Cell Differentiation in Merkel Cell Carcinomas: Clues to Cellular Ancestry

作者: Axel zur Hausen , Dorit Rennspiess , Veronique Winnepenninckx , Ernst-Jan Speel , Anna Kordelia Kurz

DOI: 10.1158/0008-5472.CAN-13-0616

关键词:

摘要: Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine nonmelanoma skin cancer, which associated with the polyoma virus (MCPyV). Recently, expression of terminal deoxynucleotidyl transferase (TdT) and paired box gene 5 (PAX 5) has been consistently reported in majority MCCs. We tested 21 MCCs for MCPyV, TdT, PAX5, IgG, IgM, IgA, kappa, lambda by immunohistochemistry assessed IgH Igk rearrangement all All revealed specific PAX5 72.8% expressed TdT. In addition, most one or more Ig subclasses kappa lambda. One MCC did reveal monoclonal next to two other showing rearrangement. As coexpression TdT under physiologic circumstances restricted pro/pre- pre-B cells we propose, on basis our results, that origin rather than postmitotic cells. MCPyV infection transformation pro-/pre-B are likely induce simple cytokeratins as shown SV40 nonepithelial This model cellular ancestry might impact therapy possibly helps understand why approximately 20% MCPyV-negative.

参考文章(30)
Ravindra Bharat Kolhe, Cynthia Cohen, Michelle D. Reid, Jeffrey R Lee, Preetha Ramalingam, Preetha Ramalingam, Immunohistochemical expression of PAX5 and TdT by Merkel cell carcinoma and pulmonary small cell carcinoma: a potential diagnostic pitfall but useful discriminatory marker International Journal of Clinical and Experimental Pathology. ,vol. 6, pp. 142- 147 ,(2013)
B S Wilson, R V Lloyd, Detection of chromogranin in neuroendocrine cells with a monoclonal antibody. American Journal of Pathology. ,vol. 115, pp. 458- 468 ,(1984)
W. W. Franke, J. Laufer, R. Moll, A. Löwe, Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies. American Journal of Pathology. ,vol. 140, pp. 427- 447 ,(1992)
Wolfgang Hartschuh, Eberhard Weihe, Ursula Egner, Chromogranin A in the mammalian merkel cell: Cellular and subcellular distribution Journal of Investigative Dermatology. ,vol. 93, pp. 641- 648 ,(1989) , 10.1111/1523-1747.EP12319788
Kishor Bhatia, James J. Goedert, Rama Modali, Liliana Preiss, Leona W. Ayers, Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression. International Journal of Cancer. ,vol. 126, pp. 2240- 2246 ,(2010) , 10.1002/IJC.24676
Cyril Toker, Trabecular Carcinoma of the Skin Archives of Dermatology. ,vol. 105, pp. 107- 110 ,(1972) , 10.1001/ARCHDERM.1972.01620040075020
Ahmad Kassem, Anja Schöpflin, Carlos Diaz, Wolfgang Weyers, Elmar Stickeler, Martin Werner, Axel zur Hausen, Frequent Detection of Merkel Cell Polyomavirus in Human Merkel Cell Carcinomas and Identification of a Unique Deletion in the VP1 Gene Cancer Research. ,vol. 68, pp. 5009- 5013 ,(2008) , 10.1158/0008-5472.CAN-08-0949
Xavier Sastre-Garau, Martine Peter, Marie-Françoise Avril, Hélène Laude, Jérôme Couturier, Flore Rozenberg, Anna Almeida, Françoise Boitier, Agnès Carlotti, Benoıt Couturaud, Nicolas Dupin, Merkel cell carcinoma of the skin: pathological and molecular evidence for a causative role of MCV in oncogenesis. The Journal of Pathology. ,vol. 218, pp. 48- 56 ,(2009) , 10.1002/PATH.2532