Endocrine Abstracts

Introduction: Papillary Thyroid cancer (PTC) accounts for 80% or more of all thyroid malignancies and genetic alterations associated with the development and progresion of this type of carcinoma remains largely unknown. Chromosomal band 11q13 seems to be one of the most frequently amplified regions in human cancer. Allelic imbalance involving EMSY, CAPN5 and PAK1 loci in thyroid cancer, have never been investigated. The aim of our study was to investigate the existence of allelic imbalance at EMSY, CAPN5 and PAK1, as candidate genes within 11q13.5-q14 region, by SNP-based LOH analysis.

Patients and methods: To investigate LOH for this region, we selected a total of 9 SNPs, that were analysed by Pyrosequencing technology among 41 samples of PTC tissue and 41corresponding normal thyroid tissue. In addition, 178 unselected controls were genotyped to estimate population frequencies of SNPs, genotypes and haplotypes in our population. The study protocol was approved by the Ethics Committee of the reference hospital.

Results: We found a complete absence of LOH at the EMSY, CAPN5, and PAK1 loci in this series of PTC patients. In addition, we used a genetic association study to determine if variation in EMSY, CAPN5 and PAK1 were associated with thyroid cancer risk. We observed differences in EMSY haplotype distribution of patients with PTC compared to general population (P=0.02, χ²=5.40; OR=2.00 [1.06–3.74]). When CAPN5 and PAK1 haplotype frequencies were compared between cases and controls, no statistical differences were observed.

Conclusions: We conclude that our studies do not support findings of LOH at EMSY, CAPN5 and PAK1 at least in thyroid cancer. We found evidence of association between EMSY haplotype and papillary thyroid cancer, suggesting that EMSY gene could be of relevance in the pathogenesis of papillary thyroid carcinoma.