title: CXCR4 expression correlates with the degree of tumor infiltration and BRAF status in papillary thyroid carcinomas.
abstract: Emerging evidence indicates that interactions between chemokine receptors and their ligands may have a critical role in several steps of tumor development, including tumor growth, progression, and metastasis. In this report, we retrospectively evaluated CXCR4 expression in a consecutive series of 200 papillary thyroid carcinomas. We investigated the relationship between the clinicopathological features of the tumors and mutations in the BRAF gene to verify whether overexpression of CXCR4 is linked to more aggressive behavior in thyroid tumors. CXCR4 protein expression was evaluated by immunohistochemical staining. A final staining score was calculated by adding the score representing the percentage of positive cells to the intensity score. The CXCR4 expression of each papillary thyroid carcinoma sample was normalized by calculating the z score for each final staining score. Univariate analysis was used to correlate CXCR4 expression with the papillary thyroid carcinoma variant, the degree of neoplastic infiltration, the American Joint Commission on Cancer stage, the presence of lymphocytic thyroiditis and the mutation status of the BRAF gene. Multiple regression analysis confirmed a strong association between CXCR4, BRAF mutation and the degree of neoplastic infiltration. These data clearly indicate that the chemokine receptor expression induced by oncogenic activation could be the major determinant of the local aggressiveness of neoplastic cells. In conclusion, our data indicate that CXCR4 expression and BRAF mutation status could cooperatively induce and promote a more aggressive phenotype in papillary thyroid carcinoma through several pathways and specifically increase the tumors' spread outside of the thyroid gland.
authors: Dipartimento di Chirurgia, Università di Pisa, Pisa, Italy.
authors: Liborio
authors: L
authors: Torregrossa
authors: Riccardo
authors: R
authors: Giannini
authors: Nicla
authors: N
authors: Borrelli
authors: Elisa
authors: E
authors: Sensi
authors: Rosa Marina
authors: RM
authors: Melillo
authors: Pietro
authors: P
authors: Leocata
authors: Gabriele
authors: G
authors: Materazzi
authors: Paolo
authors: P
authors: Miccoli
authors: Massimo
authors: M
authors: Santoro
authors: Fulvio
authors: F
authors: Basolo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D002277:Carcinoma; D002291:Carcinoma, Papillary; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000032:analysis* / Q000235:genetics; D012044:Regression Analysis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf