Identification of RET/PTC and P53 in goitrous thyroid

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Date
2003-03
Authors
Mahmood, Muhammad Hamdi
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Abstract
The goitrous enlargement of thyroid gland or nodular hyperplasia is not conventionally thought to be a precursor of malignancy. This concept has now been challenged. RET/PTC gene is a gene located in chrott1osome 10. Mutation of this gene is seen in many thyroid cancers. p53 is a tumour suppressor gene located on chromosome 17. Mutation ofp53 is seen in many human cancers including thyroid, however its expression in thyroid cancer is not ascertained. Strep-ABC immunohistochemistry approach was employed in this study to determine the prevalence of these gene products in thyroid samples obtained from the University Science Malaysia's Hospital. A total of 63 cases obtained in March 2000 to March 2001 comprised 26 cases of thyroid neoplasm of which 4 (6.4%) adenomas and 22 (34.9%) were thyroid epithelial cancers. Four (6.4%) cases of normal thyroid tissues and 33 (52.3%) cases of nodular hyperplasia were included in this study. Among the 26 cases of thyroid neoplasm, the expression of RET!PTC was seen in 3/4 (75%) adenomas, ll/12 (91.7%) papillary thyroid carcinoma, 3/3 (100%) papillary microcarcinoma, 2/3 (66.7%) follicular thyroid carcinoma, 111 (100%) HOrthle cell carcinoma, 2/2 (100%) insular carcinoma, Ill (100%) and mixed medullary papillary thyroid carcinoma. The correlation of RET/FiC expression to clinicopathologic parameters such as age (p>0.05; p=0.546), sex (p>0.05; p=0.256), race (p>0.05; p=0.68S), size of the lesion (p>0.05; p=O. 782), duration of symptoms (p>0.05; p=0.228), type of surgery (p>0.05; p=0.311) and status of disease (p>0.05; p=0.311) were all not significant. The expression of RET/PTC were significantly different (p<0.05; p=O.Ol8) between the normal (4.7%); nodular hyperplasia (28.6%); and neoplastic (36.5%) groups. The expression of RETIPTC in the surgically resected thyroid tissues showed a significantly high risk of being a carcinoma (OR=7.6334; 95% Confidence Interval 1.550-37.037; p<0.05; p=O.OOS). Survival analysis did not show any significant difference in RET/PTC expression (p>0.05; p=0.228) in the development of distant metastases among the carcinoma groups. As for p53 expression, it was seen in 3/12 (25%) papillary thyroid carcinoma, l/3 (33.3%) papillary microcarcinoma, 113 (33.3%) follicular thyroid carcinoma and absent (0.0%) in Htirthle, insular, mixed medullary papillary thyroid carcinoma & adenoma cases. The correlation of p53 expression to clinicopathologic parameters such as age (p>0.05; p=0.262), sex (p>0.05; p=0.604), race (p>0.05; p=0.588), size of the lesion (p>0.05; p=0.480), duration of symptoms (p>0.05; p=0.319), type of surgery (p>0.05; p=0.721) and status of disease (p>0.05; p=0.550) were all not significant. The p53 expressions were not significantly different (p>0.05; p=0.519) between the normel (0.0%); nodular hyperplasia (6.3%); and neoplastic (7.9%) groups. p53 expression did not significantly carry the risk of carcinoma (OR=2.427; 95% Confidence Interval 0.575-10.20; p>0.05; p=0.272). Survival analysis did not show any significant difference in p53 expression (p>0.05; p=0.989) in the development of distant metastases among the carcinoma groups. It is concluded that RET/PTC is expressed in most thyroid cancers and its presence in non-neoplastic thyroid lesion could indicate malignant/ neoplastic transformation. p53 does not seem to have this role. This knowledge enhances our understanding and opens another avenue in investigating the pathogenesis of thyroid cancer.
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RET/PTC , Goitrous thyroid
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