Naslov
Aberration of FHIT gene associated with increased tumor proliferation and decreased apoptosis - clinical evidence in lung and head and neck carcinomas
(Aberration of FIHT gene associated with increased tumor proliferation and decreased apoptosis - clinical evidence in lung and head and neck carcinomas)

Autori
Pavelić, Krešimir ; Križanac, Šimun ; Čačev, Tamara ; Popović Hadžija, Marijana ; Crnić, Ivana ; Levanat, Sonja ; Kapitanović, Sanja

Izvornik
Molecular Medicine (1076-1551) 7 (2001), 7; 442-453

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
FHIT; p21; lung cancer; HNSCC; apoptosis

Sažetak
Human FHIT (fragile histidine triad) gene is highly conserved gene homologous to a group of genes identified in prokaryotes and eukaryotes. Loss of FHIT function may be important in the development and/or progression of various types of cancer.We undertook a clinical study to analyze the relation between aberrant function of FHIT gene, tumor cell proliferation and intensity of apoptosis as well as prognostic output in lung and squamous cell head and neck carcinoma (HNSCC). Status of FHIT gene, expression of p21waf1, intensity of apoptosis and cell proliferation was analyzed in HNSCC and lung carcinoma tissues by molecular genetic methods, immunohistochemistry, [3H]-thymidine labeling method and FACScan analysis in frozen and paraffin-embedded tissue sections.The majority of the malignant lung and HNSCC lesions displayed abberant expression of FHIT gene, followed by low or negative expression of p21waf1, and increased intensity of cell proliferation. Similar results were obtained on synchronous combinations of normal, precancerous, and cancerous head and neck tissues. The observed changes increased with progression of these lesions. We examined tumor and corresponding normal tissue samples for VNTR markers D3S1300 and D3S4104 to evaluate the loss of heterozygosity (LOH) at the FHIT gene loci. We found high percentage of LOH in both lung tumors and HNSCC (75% for D3S1300 and 79% for D3S4103 in lung cancer and 87% for D3S1300 and 78% for D3S4103 in HNSCC). The median survival time for the patients suffering from lung cancer without FHIT expression was 22.46 months and that of the patients with FHIT expression 36.04 months. FHIT negative cases tended to correlate with a worse prognosis but without statistical significance. Median survival time of HNSCC patients without FHIT expression was 30.86 months and that of the patients with FHITH protein expression was 64.04 months (p<0.05). Our results show correlation between FHIT expression, low rate of apoptosis and high tumor cell proliferation. Aberrant FHIT gene could be prognostic marker in lung cancer.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA