title: Reduced pSmad2 immunodetection correlates with increased primary melanoma thickness.
abstract: Cutaneous melanoma is the most aggressive of cutaneous neoplasms. Identifying patients with an increased risk for the development of metastases is critical. This study investigates phospho-Smad2, a central factor of the transforming growth factor beta pathway, on formalin-fixed, paraffin-embedded tissues from 60 primary cutaneous melanomas (Breslow >1 mm), for its candidacy for being a prognostic marker in primary cutaneous melanoma. Phospho-Smad2 positivity was assessed for correlation with clinical parameters including Breslow index, melanoma type, survival, development of metastases, sentinel lymph node status and age. Phospho-Smad2 positivity was not associated with survival or development of metastases, suggesting that it would not be a useful prognostic marker. Despite this, we found phospho-Smad2 positivity to be correlated with low tumour thickness, indicating that as the primary tumour grows there is an increased inhibition of transforming growth factor beta signalling resulting in suppressed Smad2 phosphorylation. Additionally, phosphorylation of Smad2 in neighbouring melanoma cells and keratinocytes was interrelated, which is a further indication that Smad2 phosphorylation in primary melanoma is affected by local area microenvironmental factors. We hypothesize that the observed decrease in transforming growth factor beta signalling in thicker primary melanomas is due to the increased production of signalling inhibitors.
authors.affiliation: Department of Dermatology, University Hospital of Zürich, Zürich, Switzerland.
authors.forename: Christian D
authors.initials: CD
authors.lastname: Mnich
authors.forename: Keith S
authors.initials: KS
authors.lastname: Hoek
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Oberholzer
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.forename: Jürg
authors.initials: J
authors.lastname: Hafner
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Daniela
authors.initials: D
authors.lastname: Mihic
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010232:Paraffin / Q000494:pharmacology; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism*; D051899:Smad2 Protein / Q000096:biosynthesis*
chemical_list: D051899:Smad2 Protein; D005557:Formaldehyde; D010232:Paraffin