Caveolin-1 Expression in Papillary Thyroid Carcinoma

Objective We aimed to investigate the role of caveolin-1 in papillary thyroid carcinoma pathogenesis. Study Design Case series with chart review. Setting Institute for the Application of Nuclear Energy. Subjects and Methods We evaluated the expression of caveolin-1 in papillary thyroid carcinoma (PTC) by Western blot (WB) and compared the findings with immunohistochemical (IHC) expression of both epithelial and stromal caveolin-1 on the corresponding histological specimens. The results were related to clinicopathological features and BRAF mutation status. Results Caveolin-1 expression was found in malignant thyroid epithelium and more abundantly in tumor stroma but varied in both compartments within and between PTC subtypes. Caveolin-1 expression in the epithelium was more intense in classical PTC than in the other histological types. On the contrary, stromal caveolin-1 expression was stronger in the follicular, solid, and trabecular PTC variants than in classical PTC. Trends for down-regulation of caveolin-1 expression in epithelium and up-regulation in stroma from the classical via follicular to the solid variant were observed. The relation of WB and IHC results with clinicopathological parameters showed lower caveolin-1 tissue content in BRAF mutated tumors (P < .05), a positive correlation of epithelial caveolin-1 expression with lymph node metastasis (P < .05), and a negative association of stromal caveolin-1 expression with the degree of neoplastic infiltration and BRAF status. Conclusion Altered expression of caveolin-1 in the thyroid epithelial and stromal compartments may be involved in the pathogenesis of PTC. The potential clinical significance of caveolin-1 expression, as well as its relation to BRAF mutation status, deserves further investigation.

[1]  E. Gerner,et al.  Caveolin‐1 is a novel regulator of K‐RAS‐dependent migration in colon carcinogenesis , 2013, International journal of cancer.

[2]  M. Nikiforova,et al.  BRAF mutation detection in indeterminate thyroid cytology specimens , 2013, Cancer cytopathology.

[3]  I. Marečko,et al.  Caveolin-1 Expression in Thyroid Neoplasia Spectrum: Comparison of Two Commercial Antibodies , 2012, Disease markers.

[4]  S. Mendrinos,et al.  The metabolic interactions between tumor cells and tumor-associated stroma (TAS) in prostatic cancer , 2012, Cancer biology & therapy.

[5]  Jing Zhao,et al.  BRAF V600E mutation in papillary thyroid carcinoma , 2012 .

[6]  G. Sowa Caveolae, Caveolins, Cavins, and Endothelial Cell Function: New Insights , 2012, Front. Physio..

[7]  J. Koo,et al.  Expression of Caveolin-1, Caveolin-2 and Caveolin-3 in Thyroid Cancer and Stroma , 2012, Pathobiology.

[8]  J. Klubo-Gwiezdzinska,et al.  BRAFV600E Mutation Analysis from May-Grünwald Giemsa-Stained Cytological Samples as an Adjunct in Identification of High-Risk Papillary Thyroid Carcinoma , 2011, Endocrine pathology.

[9]  J. Phay,et al.  Role of BRAF in Thyroid Oncogenesis , 2011, Clinical Cancer Research.

[10]  T. Mak,et al.  The interaction between caveolin-1 and Rho-GTPases promotes metastasis by controlling the expression of alpha5-integrin and the activation of Src, Ras and Erk , 2011, Oncogene.

[11]  Ricardo Garcia,et al.  Biomechanical Remodeling of the Microenvironment by Stromal Caveolin-1 Favors Tumor Invasion and Metastasis , 2011, Cell.

[12]  E. Bilal,et al.  Molecular profiling of a lethal tumor microenvironment, as defined by stromal caveolin-1 status in breast cancers , 2011, Cell cycle.

[13]  Seho Park,et al.  The impact of caveolin protein expression in tumor stroma on prognosis of breast cancer , 2011, Tumor Biology.

[14]  P. Vitti,et al.  Correlation between the BRAF V600E mutation and tumor invasiveness in papillary thyroid carcinomas smaller than 20 millimeters: analysis of 1060 cases. , 2010, The Journal of clinical endocrinology and metabolism.

[15]  Stephanie L. Lee,et al.  Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. , 2009, Thyroid : official journal of the American Thyroid Association.

[16]  N. Wada,et al.  Treatment Strategy of Papillary Thyroid Carcinoma in Children and Adolescents: Clinical Significance of the Initial Nodal Manifestation , 2009, Annals of surgical oncology.

[17]  P. Ladenson,et al.  BRAF mutation testing of thyroid fine-needle aspiration biopsy specimens for preoperative risk stratification in papillary thyroid cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  C. Restall,et al.  Stromal cell expression of caveolin-1 predicts outcome in breast cancer. , 2009, The American journal of pathology.

[19]  C. McHenry,et al.  Contemporary management of papillary carcinoma of the thyroid gland , 2009, Expert review of anticancer therapy.

[20]  A. Toniato,et al.  Diagnosis, treatment, prognostic factors and long-term outcome in papillary thyroid carcinoma. , 2008, Minerva endocrinologica.

[21]  S. Savin,et al.  Thyroid peroxidase and galectin-3 immunostaining in differentiated thyroid carcinoma with clinicopathologic correlation. , 2008, Human pathology.

[22]  A. Pinchera,et al.  BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. , 2008, The Journal of clinical endocrinology and metabolism.

[23]  S. Wiseman,et al.  Caveolin-1 in tumor progression: the good, the bad and the ugly , 2008, Cancer and Metastasis Reviews.

[24]  V. Torres,et al.  Caveolin-1: an ambiguous partner in cell signalling and cancer , 2008, Journal of cellular and molecular medicine.

[25]  Electron Kebebew,et al.  The Prevalence and Prognostic Value of BRAF Mutation in Thyroid Cancer , 2007, Annals of surgery.

[26]  I. Nabi,et al.  Regulation of raft-dependent endocytosis , 2007, Journal of cellular and molecular medicine.

[27]  Ju-Han Lee,et al.  Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid , 2007, Cancer.

[28]  A. Pinchera,et al.  Correlation between B-RAFV600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature. , 2006, Endocrine-related cancer.

[29]  Raghu Kalluri,et al.  Fibroblasts in cancer , 2006, Nature Reviews Cancer.

[30]  G. Troncone,et al.  Detection of BRAF mutation in thyroid papillary carcinomas by mutant allele-specific PCR amplification (MASA). , 2006, European journal of endocrinology.

[31]  Yi‐Ju Chen,et al.  No correlation between BRAFV600E mutation and clinicopathological features of papillary thyroid carcinomas in Taiwan , 2005, Clinical endocrinology.

[32]  M. Xing,et al.  BRAF mutation in thyroid cancer. , 2005, Endocrine-related cancer.

[33]  S. Liyanarachchi,et al.  Papillary and follicular thyroid carcinomas show distinctly different microarray expression profiles and can be distinguished by a minimum of five genes. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  D. Barford,et al.  Mechanism of Activation of the RAF-ERK Signaling Pathway by Oncogenic Mutations of B-RAF , 2004, Cell.

[35]  H. Namba,et al.  Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. , 2003, The Journal of clinical endocrinology and metabolism.

[36]  Charis Eng,et al.  Caveolin-1 and caveolin-2,together with three bone morphogenetic protein-related genes, may encode novel tumor suppressors down-regulated in sporadic follicular thyroid carcinogenesis. , 2003, Cancer research.

[37]  P. Ladenson,et al.  BRAF mutation in papillary thyroid carcinoma. , 2003, Journal of the National Cancer Institute.

[38]  A. Nicholson,et al.  Mutations of the BRAF gene in human cancer , 2002, Nature.

[39]  A. Miyauchi,et al.  Caveolin-1 overexpression is an early event in the progression of papillary carcinoma of the thyroid , 2002, British Journal of Cancer.

[40]  Mina J. Bissell,et al.  Putting tumours in context , 2001, Nature Reviews Cancer.

[41]  E. Ikonen,et al.  A Caveolin Dominant Negative Mutant Associates with Lipid Bodies and Induces Intracellular Cholesterol Imbalance , 2001, The Journal of cell biology.

[42]  M. Lisanti,et al.  Caveolins, a Family of Scaffolding Proteins for Organizing “Preassembled Signaling Complexes” at the Plasma Membrane* , 1998, The Journal of Biological Chemistry.

[43]  A. Abdel‐Mageed,et al.  BRAF mutation in papillary thyroid carcinoma. , 2012, International journal of clinical and experimental medicine.

[44]  M. Loda,et al.  BRAF (V600E) mutation and the biology of papillary thyroid cancer , 2008 .