Prevalences of Gs alpha, ras, p53 mutations and ret/PTC rearrangement in differentiated thyroid tumours in a Korean population.
OBJECTIVE
In thyroid tumours, ras, Gs alpha, p53 mutations and ret/PTC rearrangement have been reported with variable prevalences in different geographical regions. We studied the prevalence of these mutations and rearrangement in thyroid tumours in a Korean population. As MDM2 and Bcl-1 protein expressions have been suggested to be associated with p53 protein, we also studied possible relationships among them.


METHODS
Eleven cases of adenomatous goitre, eight cases of follicular adenoma, five cases of follicular carcinoma and 37 cases of papillary carcinoma were included in this study. To find mutations and rearrangement, RT-PCR, SSCP and/or direct sequencing, after subcloning if necessary, were used, and immunohistochemical stainings were performed for p53, MDM2 and Bcl-2 proteins in cases of papillary carcinoma.


RESULTS
We could not find any rearrangement for ret/PTC-1, -2, -3 and mutation of Gs alpha. For the ras oncogene, K and H-ras mutations were not found, but N-ras mutations, point mutation of CAA to CGA in codon 61, were detected in one follicular adenoma (12.5%, 1/8) and one follicular carcinoma (33%, 1/3). p53 mutations were detected in only one case of papillary carcinoma (3%, 1/31: exon 8, codon 266 GGA-->GAA). In 30 cases of papillary carcinoma without p53 mutation, the prevalences of positive immunohistochemical staining were 13.3% for p53 protein, 53.3% for MDM2 protein and 56.7% for Bcl-2 protein. While over-expression of p53 protein was not significantly related to that of MDM2 and Bcl-2 proteins, over-expression of MDM2 and Bcl-2 in papillary carcinoma were associated.


CONCLUSIONS
ret/PTC rearrangement, Gs alpha, ras and p53 mutations are relatively rare in differentiated thyroid neoplasms from a Korean population, which may reflect genetic and environmental differences from patients in countries with high prevalences. P53 protein over-expression was noted in 13.3% of papillary carcinoma cases without p53 mutation and was not significantly related to MDM2 and Bcl-2 expression.
Park
K Y
KY
Department of Internal Medicine, Asan Institute for Life Sciences and Technology, Seoul, Korea.
Koh
J M
JM
Kim
Y I
YI
Park
H J
HJ
Gong
G
G
Hong
S J
SJ
Ahn
I M
IM
D000236:Adenoma / Q000737:chemistry / Q000235:genetics*; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000737:chemistry / Q000235:genetics; D018265:Carcinoma, Papillary, Follicular / Q000737:chemistry / Q000235:genetics; D029721:Drosophila Proteins; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D015321:Gene Rearrangement; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D007723:Korea; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D015513:Oncogene Proteins / Q000235:genetics; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D029721:Drosophila Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D019205:GTP-Binding Protein alpha Subunits, Gs