Clinicopathological roles of alterations of tumor suppressor gene p16 in papillary thyroid carcinoma.
BACKGROUND
Alterations of the p16 gene are common in human cancers, but their roles in thyroid cancers have not been clearly defined. The aim of the present study was to investigate the clinicopathological roles of the p16 gene in papillary thyroid carcinoma (PTC).


METHODS
p16 gene alterations were investigated in 44 patients with PTC (9 men, 35 women) by immunohistochemistry, reverse transcriptase-polymerase chain reaction and methylation-specific polymerase chain reaction. The findings were correlated with their clinicopathological features.


RESULTS
p16 protein expression, mRNA alterations, and promoter methylation were detected in 89% (n = 39), 77% (n = 33), and 41% (n = 18) of patients with PTC, respectively. There was no marked relationship between p16 protein expression, mRNA alteration, and promoter methylation. In follicular variant of PTC (FVPTC), there was a frequent lack of p16 protein expression and promoter methylation. PTCs showing p16 promoter methylation were often associated with a high AMES (age, metastasis to distant sites, extrathyroidal invasion, size) risk group and advanced pTNM (tumor-lymph node-metastasis) stages.


CONCLUSIONS
p16 gene alterations are common and correlate with histological features and biological aggressiveness in PTC, suggesting that they might play an important role in its pathogenesis.
Lam
Alfred King Yin
AK
Discipline of Pathology, School of Medicine, Griffith University, PMB 50 Gold Coast Mail Centre, Queensland, 9726, Australia. a.lam@griffith.edu.au
Lo
Chung Yau
CY
Leung
Pauline
P
Lang
Brian Hung Hin
BH
Chan
Wai Fun
WF
Luk
John M
JM
D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D012333:RNA, Messenger