Cribriform-morular variant of papillary thyroid carcinoma: a pathological and molecular genetic study with evidence of frequent somatic mutations in exon 3 of the beta-catenin gene.

摘要: The cribriform-morular variant (C-MV), an unusual and peculiar subtype of papillary thyroid carcinoma (PTC), has been observed frequently in familial adenomatous polyposis (FAP)-associated also sporadic carcinoma. In this paper, five young women with the C-MV PTC, aged 22-34 years at cancer diagnosis, are reported; two them had attenuated FAP. Grossly, one FAP-associated tumour were multicentric others solitary. Histologically, tumours encapsulated exhibited a combination cribriform, follicular, trabecular, solid, patterns growth, morular areas. Immunohistochemically, cells showed cytoplasmic expression thyroglobulin, neuron-specific enolase, epithelial membrane antigen, high- low-molecular-weight cytokeratins, vimentin, bcl-2 protein; nuclear oestrogen progesterone receptors, retinoblastoma accumulation beta-catenin. Germline mutations coli (APC) gene investigated using protein truncation test four subjects, including FAP individuals. APC mutation was identified only patient who thymidine deletion codon 512, resulting frameshift leading to premature stop codon. No loss heterozygosity loci close detected tissues from these patients. Somatic analysis exon 3 beta-catenin (CTNNB1) revealed alterations seven all individuals: serine residue (codon 29), three amino acids adjacent or threonine residues (codons 22, 39, 44), other 49, 54, 56). Moreover, each different examined patients somatic CTNNB1 gene. Taken together, data suggest that mutant contributes development PTC.