title: Molecular characterization of the desmoplastic tumor stroma in medullary thyroid carcinoma.
abstract: Medullary thyroid carcinomas are aggressive neoplasias that metastasize very early to loco-regional lymph nodes, and tumors with a desmoplastic stromal reaction have a higher incidence of lymph node metastasis. In order to characterize the desmoplastic response in thyroid cancers, we evaluated the expression pattern of three molecular markers of activated fibroblasts/myofibroblasts, namely, fibroblast activation protein alpha (FAPalpha), tenascin-C (Tn-C), and alpha-smooth muscle actin (alpha-SMA), as well as the endothelial markers endoglyx-1, CD34 and CD31 in a series of 28 metastatic and non-metastatic medullary thyroid cancers. Immunohistochemical studies demonstrated that the three fibroblast activation markers (FAPalpha, Tn-C, alpha-SMA) are consistently expressed in the peritumoral and intratumoral stromal compartment of medullary thyroid carcinomas and expression of FAPalpha and Tn-C correlated with the degree of desmoplasia determined histologically (p=0.001 for FAPalpha and p<0.001 for Tn-C). Moreover, the extent of desmoplasia as well as the expression of FAPalpha and Tn-C correlated with the presence of lymph node (LN) metastases (p=0.002, p=0.005 and p=0.002, respectively). No correlation was found between the microvessel density (neoangiogenesis) in the tumor stroma, assessed with the endoglyx-1, CD34 and CD31 markers, and the degree of desmoplasia or incidence of LN metastases. Using a bioinformatics-based search of the BioExpresstrade mark database we found in a series of 48 thyroid cancers a significant correlation between FAPalpha RNA expression and incidence of LN metastases also in papillary cancers. These findings suggest that the link between specific molecular markers of tumor stromal reaction and locoregional metastasis extends from medullary to other thyroid cancer types.
authors.affiliation: Department of Clinical Pathology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Oskar
authors.initials: O
authors.lastname: Koperek
authors.forename: Christian
authors.initials: C
authors.lastname: Scheuba
authors.forename: Christina
authors.initials: C
authors.lastname: Puri
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.forename: Christian
authors.initials: C
authors.lastname: Haslinger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rettig
authors.forename: Bruno
authors.initials: B
authors.lastname: Niederle
authors.forename: Klaus
authors.initials: K
authors.lastname: Kaserer
authors.forename: Pilar
authors.initials: P
authors.lastname: Garin Chesa
mesh_terms: D000199:Actins / Q000032:analysis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000235:genetics; D000954:Antigens, Surface / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D018276:Carcinoma, Medullary / Q000737:chemistry / Q000473:pathology*; D019295:Computational Biology; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008565:Membrane Proteins; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D012697:Serine Endopeptidases / Q000032:analysis* / Q000235:genetics; D017154:Stromal Cells / Q000737:chemistry / Q000473:pathology; D019063:Tenascin / Q000032:analysis* / Q000235:genetics; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000473:pathology*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000199:Actins; D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012697:Serine Endopeptidases; D019063:Tenascin; D000099167:Fibroblast Activation Protein Alpha; C089826:EMILIN3 protein, human