Aberrant Expression of Posterior HOX Genes in Well Differentiated Histotypes of Thyroid Cancers

Fabiana Tatangelo,Monica Cantile,Maria Chiofalo,Franco Fulciniti,Gerardo Botti,Elena Valentino,Elvira La Mantia,Lucia La Sala,Luciano Pezzullo,Simona Losito,Giosuè Scognamiglio,Veronica Scaramuzza,Renato Franco

doi:10.3390/ijms141121727

Abstract

Molecular etiology of thyroid cancers has been widely studied, and several molecular alterations have been identified mainly associated with follicular and papillary histotypes. However, the molecular bases of the complex pathogenesis of thyroid carcinomas remain poorly understood. HOX genes regulate normal embryonic development, cell differentiation and other critical processes in eukaryotic cell life. Several studies have shown that HOX genes play a role in neoplastic transformation of several human tissues. In particular, the genes belonging to HOX paralogous group 13 seem to hold a relevant role in both tumor development and progression. We have identified a significant prognostic role of HOX D13 in pancreatic cancer and we have recently showed the strong and progressive over-expression of HOX C13 in melanoma metastases and deregulation of HOX B13 expression in bladder cancers. In this study we have investigated, by immunohistochemisty and quantitative Real Time PCR, the HOX paralogous group 13 genes/proteins expression in thyroid cancer evolution and progression, also evaluating its ability to discriminate between main histotypes. Our results showed an aberrant expression, both at gene and protein level, of all members belonging to paralogous group 13 (HOX A13, HOX B13, HOX C13 and HOX D13) in adenoma, papillary and follicular thyroid cancers samples. The data suggest a potential role of HOX paralogous group 13 genes in pathogenesis and differential diagnosis of thyroid cancers.

Highlights

Thyroid tumors are the most common tumors of the endocrine system (1% of all cancers).Approximately 94% of thyroid cancers are well-differentiated forms, 5% are represented by medullary carcinoma and the remaining 1% anaplastic carcinomas [1]
Several studies have demonstrated that HOX genes play a role in neoplastic transformation in several human tissues [6,7,8,9,10]
The genes belonging to HOX paralogous group 13 seem to carry out a relevant role in both tumor development and progression

Summary

Introduction

94% of thyroid cancers are well-differentiated forms (papillary and follicular), 5% are represented by medullary carcinoma and the remaining 1% anaplastic carcinomas [1]. In recent years the progressive knowledge of the molecular mechanisms involved in thyroid transformation have allowed the association of alterations of specific markers to several thyroid tumor histotypes [2] permitting the formulation of a rather accurate model of tumorigenesis, not yet fully defined [3]. The prognosis of thyroid cancer remains unpredictable, the identification of new biological markers are needed in addition to already known molecules, to correctly stratify patients at risk of recurrence and progression. The genes belonging to HOX paralogous group 13 seem to carry out a relevant role in both tumor development and progression

Methods

Results

Discussion

Conclusion