title: Cyclin D1 in well differentiated thyroid tumour of uncertain malignant potential.
abstract: BACKGROUND
  Encapsulated follicular tumours with equivocal papillary thyroid carcinoma (PTC) type nuclear features continue to remain a challenge despite the recent attempts to classify these borderline lesions. The term 'well differentiated tumour of uncertain malignant potential (WDT-UMP)' was introduced to classify these tumours. The present study aimed to evaluate the role of a cell cycle regulator like cyclin D1 in these tumours along with assessment of other well established PTC markers like galectin-3, HBME-1, CK19.
  
  
  METHODS
  Thirteen cases of metastatic PTC, papillary microcarcinoma and follicular variant of PTC (FVPTC) were identified from a histological review of 510 cases. In addition, 13 cases of a subset of follicular adenomatoid nodules with focal areas showing nuclear features characteristic of PTC, identified as WDT-UMP, were also analyzed. Immunohistochemical analysis of galectin-3, HBME-1, CK19 and the proliferation markers Ki67 and cyclin D1 was performed. Lesions were analyzed for cyclin D1 gene amplification by fluorescent in-situ hybridization.
  
  
  RESULTS
  All WDT-UMP lesions showed immunolabelling of cyclin D1, Ki67; 11/ 13 cases showed immunolabelling of CK19; 10/13 cases showed immunolabelling of HBME-1 and 4/13 cases showed immunolabelling of galectin-3. Surrounding benign adenomatoid areas showed no to faint focal staining in all thirteen cases of cyclin D1, HBME-1 and galectin-3. A low rate of cyclin D1 gene amplification was identified in a significant proportion of cells in the WDT-UMP lesions as compared to surrounding benign adenomatoid areas.
  
  
  CONCLUSIONS
  Increased expression of cyclin D1 and amplification of its gene along with immunolabelling of HBME-1 in WDT-UMP lesions showing cytological features of papillary thyroid carcinoma within follicular adenomatoid nodules suggest that these areas could correspond to a precursor lesion of follicular variant of PTC. Overexpression of cyclin D1, associated with the amplification of the gene suggests that these WDT-UMP lesions are an intermediate between the benign and malignant groups making this group of lesions a reliable precursor of FVPTC.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1851820807142117.
authors.affiliation: Anatomie pathologique, Cliniques universitaires Saint- Luc, Université catholique de Louvain, Avenue Hippocrate, 10/T-1, Brussels, 1200, Belgium. monikalamba@gmail.com.
authors.forename: Monika
authors.initials: M
authors.lastname: Lamba Saini
authors.affiliation: Anatomie pathologique, CHU Dinant-Godinne, Université catholique de Louvain, Avenue Docteur G. Thérasse, 1, Yvoir, 5530, Belgium. birgitweynand@uclouvain.be.
authors.forename: Birgit
authors.initials: B
authors.lastname: Weynand
authors.affiliation: Anatomie pathologique, Cliniques universitaires Saint- Luc, Université catholique de Louvain, Avenue Hippocrate, 10/T-1, Brussels, 1200, Belgium. jacques.rahier@uclouvain.be.
authors.forename: Jacques
authors.initials: J
authors.lastname: Rahier
authors.affiliation: Service de transplantation rénale et chirurgie endocrinologique, Cliniques universitaires Saint-Luc, Université catholique de Louvain, B-1200, Bruxelles, Belgium. michel.mourad@uclouvain.be.
authors.forename: Michel
authors.initials: M
authors.lastname: Mourad
authors.affiliation: Service d'oto-rhino-laryngologie et chirurgie cervico-faciale, Cliniques universitaires Saint-Luc, Université catholique de Louvain, B-1200, Bruxelles, Belgium. marc.hamoir@uclouvain.be.
authors.forename: Marc
authors.initials: M
authors.lastname: Hamoir
authors.affiliation: Anatomie pathologique, Cliniques universitaires Saint- Luc, Université catholique de Louvain, Avenue Hippocrate, 10/T-1, Brussels, 1200, Belgium. etienne.marbaix@uclouvain.be.
authors.forename: Etienne
authors.initials: E
authors.lastname: Marbaix
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D001798:Blood Proteins; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation; D019938:Cyclin D1 / Q000032:analysis* / Q000235:genetics; D005260:Female; D037502:Galectin 3 / Q000032:analysis; D037161:Galectins; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053539:Keratin-19 / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation; D000951:Antigens, Neoplasm
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D019938:Cyclin D1; D037502:Galectin 3; D037161:Galectins; D053539:Keratin-19; D019394:Ki-67 Antigen; C530104:CCND1 protein, human; C432845:HBME-1 antigen; D000951:Antigens, Neoplasm; C428445:LGALS3 protein, human