Expression profiles associated with aggressive behavior in Merkel cell carcinoma.
Primary neuroendocrine carcinoma of the skin, or Merkel cell carcinoma, is the most aggressive cutaneous neoplasm. In spite of its similarities to small cell carcinomas from other locations, Merkel cell carcinoma shows many peculiarities probably related to its epidermal origin and the etiologic role of UV radiation. We have immunohistochemically investigated 43 markers on a tissue microarray in which 31 surgically resected Merkel cell carcinomas were represented. Of these, 15 patients remained free of disease after removal, whereas 16 developed metastases. Immunoreactivity was scored according to staining intensity and the percentage of positive cells. We found statistically significant correlations between metastatic tumor spread and overexpression of matrix metalloproteinase (MMP) 7, MMP10/2, tissue inhibitor of metalloproteinase 3, vascular endothelial growth factor (VEGF), P38, stromal NF-kappaB, and synaptophysin. Also detected were statistically significant correlations between the expression levels of MMP7 and VEGF, MMP7 and P21, MMP7 and P38, MMP10/2 and VEGF, P38 and synaptophysin, P38 and P53, and P21 and stromal NF-kappaB. These findings may be helpful in predicting the clinical course of Merkel cell carcinoma and are potentially useful for the development of targeted therapies.
Fernández-Figueras
María-Teresa
MT
Department of Pathology, Hospital Universitari Germans Trias i Pujol, Autonomous University of Barcelona, Barcelona, Spain. 20669mtf@comb.es
Puig
Lluís
L
Musulén
Eva
E
Gilaberte
Montserrat
M
Lerma
Enrique
E
Serrano
Sergio
S
Ferrándiz
Carlos
C
Ariza
Aurelio
A
D014408:Biomarkers, Tumor / Q000032:analysis*; D015266:Carcinoma, Merkel Cell / Q000737:chemistry / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology*; D053505:Matrix Metalloproteinases, Secreted / Q000032:analysis; D016328:NF-kappa B / Q000032:analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012878:Skin Neoplasms / Q000737:chemistry / Q000473:pathology*; D013030:Spain; D016708:Synaptophysin / Q000032:analysis; D013997:Time Factors; D046888:Tissue Array Analysis; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016328:NF-kappa B; D016708:Synaptophysin; C088390:TIMP3 protein, human; C495901:TP53 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D048051:p38 Mitogen-Activated Protein Kinases; D053505:Matrix Metalloproteinases, Secreted