Expression of hedgehog signaling molecules in Merkel cell carcinoma.
BACKGROUND
The Hedgehog signaling pathway is important for human development and carcinogenesis in various malignancies.


METHODS
One tissue microarray with triplets of 28 samples from 25 patients with Merkel cell carcinoma (MCC) was constructed. Six samples of normal skin and 5 samples of normal oral mucosa served as controls. All samples were analyzed immunohistochemically with antibodies directed against Sonic hedgehog, Indian hedgehog, Patched, Smoothened, Gli-1, Gli-2, and Gli-3.


RESULTS
All investigated proteins were frequently and intensely overexpressed in MCCs (Sonic hedgehog, 93%; Indian hedgehog, 84%; Patched, 86%; Smoothened, 79%; Gli-1, 79%; Gli-2, 79%; Gli-3, 86%) compared with control samples. High levels of Patched and Indian hedgehog were significantly associated with an increase in patients overall (p = .015) and recurrence-free survival (p = .011), respectively.


CONCLUSIONS
Our results indicate that the Hedgehog signaling pathway is strongly activated in MCC and thus may play a role in carcinogenesis.
Brunner
Markus
M
Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
Thurnher
Dietmar
D
Pammer
Johannes
J
Heiduschka
Gregor
G
Petzelbauer
Peter
P
Schmid
Christoph
C
Schneider
Sven
S
Erovic
Boban M
BM
D000368:Aged; D000369:Aged, 80 and over; D015266:Carcinoma, Merkel Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D000072079:Patched Receptors; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
C400551:GLI1 protein, human; C082593:GLI2 protein, human; C065683:GLI3 protein, human; D053823:Hedgehog Proteins; C509246:IHH protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3