title: PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma.
abstract: BACKGROUND
  PTEN gene at chromosomes 10q23.3 is a tumour suppressor gene that is inactivated in many types of human cancers. The known mechanisms of PTEN inactivation are rendered to mutation, epigenetic silencing by aberrant methylation or gene deletion. Although PTEN role has been documented in many cancers, PTEN alteration in papillary thyroid carcinoma (PTC) has not been fully elucidated. The aim of this study is to comprehensively investigate PTEN alterations in a large cohort of Middle Eastern papillary thyroid cancer by immunohistochemistry and fluorescent in situ hybridisation (FISH).
  
  
  METHODS
  PTEN protein expression was analysed by immunohistochemistry in a tissue microarray (TMA) format in a large cohort of more than 1000 patients with papillary thyroid cancer. Copy number changes in PTEN were analysed by FISH and data were correlated with clinicopathological parameters along with survival analysis.
  
  
  RESULTS
  PTEN inactivation reflected by complete absence of staining was seen in 24.5% of PTC samples, whereas PTEN deletion was seen only in 4.8% of the tested samples by FISH. No association was seen between PTEN loss of protein expression and PTEN gene deletion. However, interestingly, PTEN loss of expression was significantly associated with the follicular variant subset of papillary thyroid cancer.
  
  
  CONCLUSIONS
  Our study confirmed that PTEN might have a role in pathogenesis in a subset of PTC. PTEN loss of protein expression is a more common event in follicular variant of papillary thyroid cancer. Lack of association between PTEN loss of protein expression and PTEN gene deletion might indicate that gene deletion may not be the sole cause for PTEN loss of expression and these results might raise the possibility of other mechanism such as promoter methylation-mediated gene silencing to be responsible for PTEN inactivation.
authors.affiliation: Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Beg
authors.affiliation: Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: A K
authors.initials: AK
authors.lastname: Siraj
authors.affiliation: Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Z
authors.initials: Z
authors.lastname: Jehan
authors.affiliation: Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Prabakaran
authors.affiliation: Department of Surgery, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: S S
authors.initials: SS
authors.lastname: Al-Sobhi
authors.affiliation: Department of Diabetes and Endocrinology, Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Al-Dawish
authors.affiliation: Department of Pathology, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: F
authors.initials: F
authors.lastname: Al-Dayel
authors.affiliation: 1] Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia [2] Department of Pathology, College of Medicine, Alfaisal University, P.O. Box 3354, 11211 Riyadh, Saudi Arabia.
authors.forename: K S
authors.initials: KS
authors.lastname: Al-Kuraya
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics; D002291:Carcinoma, Papillary; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D008877:Middle East; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D025521:Tumor Suppressor Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human