“The potential role of CXCR4 and SDF-1 as indicators of tumor aggressiviness in patients with conventional papillary thyroid carcinoma”

Pagano, Loredana (2008) “The potential role of CXCR4 and SDF-1 as indicators of tumor aggressiviness in patients with conventional papillary thyroid carcinoma”. [Tesi di dottorato] (Inedito)

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Abstract

Background: Functional chemokine receptors are expressed in many malignant tumors, including papillary thyroid carcinoma (PTC). These receptors promote tumor growth and metastasis in response to endogenous chemokines. The purpose of this study was to examine the expression of SDF-1 and its chemokine receptors, CXCR4, in a series of PTCs, considered as low risk for tumor size and hystotypes. In this study, we correlated CXCR4 and SDF-1 with indicators of clinical and tumor aggressiveness, including age, gender, tumor size, extrathyroidal extension, multifocality and lymph node metastasis. Methods: CXCR4 as well as its specific chemokine ligand, SDF-1 , were assessed in 48 PTCs using a semiquantitative measure of immunohistochemical (IHC) staining intensity for each molecule. Staining intensity was compared with clinicopathological features. Expression in CXCR4 and SDF-1 mRNA levels were sought in a subset of tumors, using gene microarrays and quantitative RTPCR. Results: In 29 cases, the PTC was associated with chronic thyroiditis. High-intensity IHC staining for CXCR4 correleted with T1 (p=0.003), classical variant (p=0.02) and lymph node metastasis at initial diagnosis (p=0.01). In contrast SDF 1 correlated with female gender (p =0.05), but this association was not shown following multivariate analyses. Conclusion: In our study, the expression of CXCR4 and its ligand are more frequent in tumors that have a smaller dimension and a classical variant of PTC. Therefore, CXCR4 and its ligand are associated with lymph node metastasis involvement at the initial diagnosis, which is an indicator of negative prognosis. Finally, the chemokine pathways may be expressed early in PTC tumorigenesis. Although these markers are found in a less aggressive PTC variant, they may be responsible for early and preferential lymphnode neck metastases. Further studies are necessary to define the mechanisms underlying this association and to determine its potential prognostic and therapeutic implications.

Tipologia di documento:Tesi di dottorato
Parole chiave:Papillary thyroid carcinoma, chemokines, SDF-1 and CXCR4, chronic thyroiditis and thyroid cancer
Settori scientifico-disciplinari MIUR:Area 06 Scienze mediche > MED/13 ENDOCRINOLOGIA
Coordinatori della Scuola di dottorato:
Coordinatore del Corso di dottoratoe-mail (se nota)
Vecchio, Giancarlovecchio@unina.it
Tutor della Scuola di dottorato:
Tutor del Corso di dottoratoe-mail (se nota)
Biondi, Bernadette
Stato del full text:Accessibile
Data:Novembre 2008
Numero di pagine:71
Istituzione:Università degli Studi di Napoli Federico II
Dipartimento o Struttura:Dipartimento di Oncologia ed Endocrinologia Molecolare e Clinica
Tipo di tesi:Dottorato
Stato dell'Eprint:Inedito
Scuola di dottorato:Medicina Molecolare
Denominazione del dottorato:Oncologia ed Endocrinologia Molecolare
Ciclo di dottorato:XXI
Numero di sistema:3297
Depositato il:13 Novembre 2009 12:12
Ultima modifica:13 Novembre 2009 12:12

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