Clinicopathological significance of the fragile histidine triad transcription protein expression in laryngeal carcinogenesis.
The fragile histidine triad (FHIT), frequently lost in many cancers, was identified as a candidate tumor suppressor gene at chromosome 3p locus 14.2. Loss of the FHIT protein because of the alteration or loss of heterozygosity by genetic deletion occurs in a variety of epithelial tumors including head and neck cancer. However, the biological function of the FHIT protein is still unknown and its role in intrinsic cellular proliferation remains particularly controversial in preinvasive lesions and invasive tumors of the head and neck. To clarify the role of the FHIT protein in laryngeal squamous cell carcinoma (LSCC) and to examine whether the expression of FHIT could be a prognostic parameter for laryngeal carcinogenesis, we investigated the relationship between the expression of the FHIT protein, other tumor suppressor gene products (p53 and p16), the cellular proliferation marker (Ki-67) and the survival time of patients with LSCC. In our study, there were significant differences (p<0.05) in the expression of FHIT between low grade dysplasia and LSCC. Additionally, survival time analysis showed a significant correlation between the reduction of FHIT expression and the length of disease-free survival (p<0.05) in patients with T1-T2 N0 laryngeal carcinoma. However, we did not confirm a relationship between the expression of FHIT, the other tumor suppressor gene products (p53 and p16) or the cellular proliferation marker (Ki-67). In conclusion, we provided evidence that the reduction of FHIT levels may be a useful prognostic indicator for the clinical outcome of laryngeal SCC. Our findings indicated that FHIT utilizes a pathway independent of p53 and is involved in abnormal cell proliferation via the breakdown of G0-G1 arrest in the larynx and apoptosis during multistep carcinogenesis of the larynx.
Kitamura
Koichi
K
Department of Otolaryngology, Tokyo Medical University, Tokyo, Japan. k-kita@wd5.so-net.ne.jp
Hayashi
Ken
K
Kobayashi
Ryo
R
Ishii
Hideaki
H
Matsubayashi
Jun
J
Matsumoto
Tetsuya
T
Suzuki
Mamoru
M
D017766:Acid Anhydride Hydrolases / Q000032:analysis* / Q000235:genetics; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D000099170:Bis(5'-adenosyl)triphosphatase