title: Expression of hypoxia-inducible factor 1 alpha in papillary thyroid carcinoma is associated with desmoplastic stromal reaction and lymph node metastasis.
abstract: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, and it early metastasizes into regional lymph nodes. We evaluated immunohistochemically the expression of the hypoxia marker hypoxia-inducible factor 1α (HIF-1α) as well as extracellular matrix protein tenascin C as a marker of stroma remodelling in a cohort of 160 PTCs. Expression of HIF-1α was seen focally accentuated in 100 of the 160 tumours (62.5 %) including 16 cases with equivocal staining (faint staining or only single-cell staining) and 84 cases with unequivocal staining. HIF-1α expression correlated with the degree of desmoplastic stromal reaction as well as with the expression of tenascin C (p < 0.001, Kruskal-Wallis test, respectively). Moreover, expression of HIF-1α was significantly associated with the presence of lymph node metastases (p < 0.001, Mann-Whitney test) as well as signs of invasion, namely, peritumoural and extrathyroidal invasion as well as angioinvasion (p = 0.024, p < 0.001, p = 0.017, Mann-Whitney test, respectively). Additionally, PTC with unequivocal HIF-1α nuclear staining was a larger tumour than PTC with negative (-) or equivocal HIF-1α expression (p < 0.001, Kruskal-Wallis test). Interestingly, the expression of HIF-1α was not significantly associated with BRAF V600E status (p > 0.05, Mann-Whitney test). Our data show that the expression of HIF-1α is associated with stroma remodelling processes within the tumour and, thus, may play an important role in an invasive behaviour of these tumours independent of BRAF mutation status.
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria, oskar.koperek@meduniwien.ac.at.
authors.forename: Oskar
authors.initials: O
authors.lastname: Koperek
authors.forename: Erol
authors.initials: E
authors.lastname: Akin
authors.forename: Reza
authors.initials: R
authors.lastname: Asari
authors.forename: Bruno
authors.initials: B
authors.lastname: Niederle
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Neuhold
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002291:Carcinoma, Papillary; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D012189:Retrospective Studies; D019063:Tenascin / Q000032:analysis / Q000096:biosynthesis; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D059016:Tumor Microenvironment / Q000502:physiology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019063:Tenascin