Gambichler, T., Mohtezebsade, S., Wieland, U., Silling, S., Hoeh, A. -K., Dreissigacker, M., Schaller, J., Schulze, H. -J., Oellig, F., Kreuter, A., Stockfleth, E., Stuecker, M., Bechara, F. G. and Becker, J. C. (2017). Prognostic relevance of high atonal homolog-1 expression in Merkel cell carcinoma. J. Cancer Res. Clin. Oncol., 143 (1). S. 43 - 50. NEW YORK: SPRINGER. ISSN 1432-1335

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Abstract

Background It has recently been reported that atonal homolog 1 (ATOH1) gene is down-regulated in Merkel cell carcinoma (MCC) and thus may represent a tumor suppressor gene. Objectives We aimed to test for ATOH1 gene mutations and expression levels in MCC tissues and cell lines. Methods Genomic DNA isolation and amplification via PCR was successfully performed in 33 MCCs on formalin-fixed paraffin-embedded tissue and three MCC cell lines, followed by Sanger sequencing of the whole ATOH1 gene to detect genomic aberrations. ATOH1 mRNA levels were determined by RT-PCR. Immunohistochemistry of ATOH1 was performed to quantify protein expression in tumor samples and cell lines. Results Neither in any of the 33 MCC tissue samples nor in the three cell lines ATOH1 mutations were present. ATOH1 was expressed in all lesions, albeit at different expression levels. Univariate analysis revealed that the total immunohistology score significantly correlated with the occurrence of tumor relapse (r = 0.57; P = 0.0008). This notion was confirmed in multivariate analysis suggesting that ATOH1 expression is a potential independent predictor for tumor relapse in MCC patients (P = 0.028). MCC-related death also correlated with ATOH1 expression (r = 0.4; P = 0.025); however, ATOH1 expression did not retain its predictive value in the regression model. Conclusions In contrast to anecdotal reports ATOH1 expression is not lost by genetic alterations in MCC. However, protein expression of ATOH1 is increased in advanced MCC indicating that ATOH1 is involved in MCC progression.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gambichler, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mohtezebsade, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wieland, U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Silling, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoeh, A. -K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dreissigacker, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaller, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulze, H. -J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oellig, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreuter, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stockfleth, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stuecker, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bechara, F. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, J. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-247703
DOI: 10.1007/s00432-016-2257-6
Journal or Publication Title: J. Cancer Res. Clin. Oncol.
Volume: 143
Number: 1
Page Range: S. 43 - 50
Date: 2017
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-1335
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
POLYOMAVIRUS; DIFFERENTIATION; MEDULLOBLASTOMA; ATOH1; HATH1; NOMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/24770

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