Tuesday, May 19, 2009

Molecular pathogenesis of Merkel cell carcinoma

Molecular pathogenesis of Merkel cell carcinoma

Exp Dermatol. 2009 Mar
Houben R, Schrama D, Becker JC.
Department of Dermatology, Julius Maximilians University, Würzburg, Germany.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer which is twice as lethal as melanoma as more than one-third of MCC patients will die from this cancer. Although MCC, which primarily affects elderly and immune suppressed individuals, is very rare to date, its incidence is rapidly increasing. In contrast to the immense progress that has been made in the elucidation of the molecular pathogenesis of other cancer entities, until recently there were no clear-cut indications which events drive the carcinogenesis of MCC. Important findings published last year have changed this radically. Hypermethylation of the p14(ARF) promoter and a striking correlation between expression of p63 and the clinical course of MCC have been reported. Most important, however, is the discovery that MCC development in the majority of cases is preceded by the integration of genomic sequences of the hitherto unknown Merkel cell polyomavirus (MCPyV). Now a fundamental improvement in the understanding of MCC pathogenesis as well as the development of new therapeutic approaches based on this knowledge appear to be possible within the near future.


Merkel cell carcinoma--immunohistochemical study in a group of 11 patients

Merkel cell carcinoma--immunohistochemical study in a group of 11 patients
Jirásek T, Matej R, Pock L, Knotková I, Mandys V.
Ustav patologie 3, LF UK a FNKV, Praha.

The aim of our work was to confirm an immunohistochemical profile of routine markers of epithelial and neuroendocrine differentiation in eleven cases of Merkel cell carcinoma, as well as to study the expression of two markers of early phases of neuronal differentiation, namely reelin and class III beta-tubulin, markers which have not yet been studied in Merkel cell carcinomas. In all the investigated tumours the characteristic "dot-like" pattern of cytokeratin 20 immunoexpression, as well as negative immunostaining for cytokeratin 7 and thyroid transcription factor 1 (TTF-1) were disclosed; all the tumours showed neuroendocrine differentiation, expressing either neuron specific enolase (NSE) or chromogranin A(CgA), or both. An interesting finding was observed when the anti-cytokeratin monoclonal antibody MNF 116 was used. The characteristic "dot-like" pattern was detected in high proportion of tumours, including two samples of local recurrence of one of the carcinomas, where neoplastic cells have lost the expression of cytokeratin 20. The majority (91%) of Merkel cell carcinomas included in our group showed positive immunodetection of class III beta-tubulin when TU-20 antibody was used, while TuJ-1 immunostaining was surprisingly negative in all the investigated tumours. Detection of reelin was negative in almost all the studied Merkel cell carcinomas except for cases, where neoplastic cells revealed weak focal immunostaining in a minor portion of neoplastic cells.

PMID: 19402315 [PubMed - in process]

Merkel cell carcinoma: a review of current advances.

Merkel cell carcinoma: a review of current advances.

Zhan FQ, Packianathan VS, Zeitouni NC.
Department of Dermatology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous malignancy of neuroendocrine origin. Its incidence has tripled over the past 15 years. This article reviews the recent advancement in diagnosis, discoveries in pathogenesis, and updates in management. The acronym, AEIOU, has been proposed to aid in clinical identification. In addition to cytokeratin 20, newer immunohistochemical stains (in particular thyroid transcription factor-1 and neurofilament protein) have proven to be essential in pathologic diagnosis. Although immune suppression and ultraviolet radiation have long been associated with the MCC oncogenesis, recent studies also show involvement of a new polyomavirus and bcl-2. Several tumor classifications have been published in the literature, with the 4-tiered system from Memorial Sloan-Kettering Cancer Center the most widely used. A similar classification with additional distinctions among nodal disease is being constructed. A multidisciplinary treatment algorithm is recommended for MCC. Surgical excision with adjuvant radiotherapy (RT) is indicated for localized tumors. RT is favored over complete lymph node dissection and chemotherapy for regional lymph node involvement. For distant metastasis, management should be individualized with a combination of palliative surgery, RT, and chemotherapy.

PMID: 19401065 [PubMed - in process]