Universität zu Köln

Helbig, Doris, Ihle, Michaela Angelika, Puetz, Katharina, Tantcheva-Poor, Iliana, Mauch, Cornelia, Buettner, Reinhard and Quaas, Alexander (2016). Oncogene and therapeutic target analyses in Atypical fibroxanthomas and pleomorphic dermal sarcomas. Oncotarget, 7 (16). S. 21763 - 21775. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

Background: Until now, almost nothing is known about the tumorigenesis of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). Our hypothesis is that AFX is the non-infiltrating precursor lesion of PDS. Materials and Methods: We performed the world-wide most comprehensive immunohistochemical and mutational analysis in well-defined AFX (n=5) and PDS (n=5). Results: In NGS-based mutation analyses of selected regions by a 17 hotspot gene panel of 102 amplicons we could detect TP53 mutations in all PDS as well as in the only analyzed AFX and PDS of the same patient. Besides, we detected mutations in the CDKN2A, HRAS, KNSTRN and PIK3CA genes. Performing immunohistochemistry for CTNNB1, KIT, CDK4, c-MYC, CTLA-4, CCND1, EGFR, EPCAM, ERBB2, IMP3, INI-1, MKI67, MDM2, MET, p40, TP53, PD-L1 and SOX2 overexpression of TP53, CCND1 and CDK4 was seen in AFX as well as in PDS. IMP3 was upregulated in 2 AFX (weak staining) and 4 PDS (strong staining). FISH analyses for the genes FGFR1, FGFR2 and FGFR3 revealed negative results in all tumors. Conclusion: UV-induced TP53 mutations as well as CCND1/CDK4 changes seem to play essential roles in tumorigenesis of PDS. Furthermore, we found some more interesting mutated genes in other oncogene pathways (activating mutations of HRAS and PIK3CA). All AFX and PDS investigated immunohistochemically presented with similar oncogene expression profiles (TP53, CCND1, CDK4 overexpression) and the single case with an AFX and PDS showed complete identical TP53 and PIK3CA mutation profiles in both tumors. This reinforces our hypothesis that AFX is the non-infiltrating precursor lesion of PDS.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Helbig, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED Ihle, Michaela Angelika UNSPECIFIED UNSPECIFIED UNSPECIFIED Puetz, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Tantcheva-Poor, Iliana UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-278502
DOI:	10.18632/oncotarget.7845
Journal or Publication Title:	Oncotarget
Volume:	7
Number:	16
Page Range:	S. 21763 - 21775
Date:	2016
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ONCOFETAL PROTEIN IMP3; SQUAMOUS-CELL CARCINOMA; KINETOCHORE GENE KNSTRN; DIAGNOSTIC BIOMARKER; IDH2 MUTATIONS; BREAST-CANCER; P53 MUTATION; LUNG-CANCER; EXPRESSION; PIK3CA Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27850