Molecular genetic alterations of FHIT and p53 genes in benign and malignant thyroid gland lesions.
Several oncogenes and tumor-suppressor genes are involved either as early or late event in thyroid gland carcinogenesis. Human FHIT (fragile histidine triad) gene is highly conserved gene whose loss of function may be important in the development and/or progression of various types of cancer. We undertook this study to analyze FHIT and p53 gene status in different benignant and malignant thyroid tumors. Status of these genes as well as intensity of apoptosis was analyzed in tumor tissues by molecular genetic methods, immunohistochemistry, and FACS-scan analysis. The majority of the malignant thyroid cancers displayed aberrant expression of FHIT gene, concominant with p53 gene inactivation. This is followed by low rate of apoptosis, which may be important in the development and/or progression of thyroid cancer. We found higher incidence of p53 mutation and aberrant processing of FHIT mRNA in malignant tumors (papillary, follicular, medullary and anaplastic carcinomas) and in those tumors with distant metastasis. The growth of p53(-)/FHIT(-) follicular carcinoma of human origin was much faster in nude mice than p53(+)/FHIT(+) follicular carcinoma, and mice had shorter survival rate. Our results show a correlation between aberrant FHIT and p53 expression, low rate of apoptosis, and malignancy. Concomitant aberration of FHIT gene and p53 could be responsible for development of highly malignant types of thyroid cancer and may be considered as a prognostic marker for these tumors.
Pavelić
Kresimir
K
Division of Molecular Medicine, Ruder Bosković Institute, Zagreb, Croatia. pavelic@irb.hr
Dedivitis
Rogerio A
RA
Kapitanović
Sanja
S
Cacev
Tamara
T
Guirado
Cristiano R
CR
Danić
Davor
D
Radosević
Senka
S
Brkić
Kornelije
K
Pegan
Boris
B
Krizanac
Simun
S
Kusić
Zvonko
Z
Spaventi
Sime
S
Bura
Miljenko
M
D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D013959:Thyroid Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase