Immunohistochemical localisation of RET and p53 mutant protein of thyroid lesions in a North-Eastern Malaysian population and its prognostic implications.
OBJECTIVE
To investigate RET and p53 expression in local thyroid lesions, in order to shed light on the pathogenesis of papillary carcinoma and explain the high prevalence of this condition among the nodular hyperplasia (multi-nodular goitre) cases.


METHODS
Archival thyroid tissue was retrieved from Hospital Universiti Sains Malaysia (HUSM) Pathology Department files and studied by immunohistochemistry for RET and p53 mutant protein. Normal tissues from 74 cases served as controls.


RESULTS
Fifty follicular adenoma, 66 nodular hyperplasia and 53 papillary carcinoma cases were studied. RET was expressed in 5.4% of normal thyroid tissue, 18% of follicular adenomas, 22.7% of nodular hyperplasia cases and 71.7% of papillary carcinomas. Its expression in papillary carcinoma was not associated with the coexistence of nodular hyperplasia lesions. p53 was expressed by 17% of papillary carcinomas. No association was found between p53 expression of nodular hyperplasia with or without co-existing papillary carcinoma. p53, rather than RET, was an excellent predictor of tumour lymph node metastasis and capsular invasion. p53 was also a significant prognosticator of survival outcome.


CONCLUSIONS
RET expression is highly prevalent in local papillary carcinoma, indicating a significant role in the pathogenesis of this tumour, with no apparent role in tumour behaviour and survival outcome. p53 on the other hand appears to be a significant factor in the latter events. The two genes appear to act in two different pathways: the former being an initiator, and the later a propagator of papillary carcinoma.
Omar
Effat
E
Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia.
Madhavan
Manoharan
M
Othman
Nor Hayati
NH
D000231:Adenocarcinoma, Papillary / Q000453:epidemiology / Q000378:metabolism* / Q000556:secondary; D000236:Adenoma / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006044:Goiter, Nodular / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D013965:Thyroidectomy; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases