title: Fragile histidine triad protein expression in nonsmall cell lung cancer and correlation with Ki-67 and with p53.
abstract: Fragile histidine triad (FHIT) is a tumour suppressor gene, which is altered in a variety of epithelial tumours, including lung cancer. Biochemical and functional pathways of its tumourigenicity are not yet understood. Its role in tumour proliferation is particularly controversial. The purpose of this study was to correlate the expression of FHIT protein in nonsmall cell lung cancer (NSCLC) with tumour proliferation as estimated by Ki-67 antigen and with p53, a suppressor gene. FHIT, Ki-67 and p53 expression were evaluated by immunohistochemistry in 119 resected NSCLC. Altogether, 58 tumours were negative (expression <10%) for FHIT. The median expression in tumours was 15% positive cells, in comparison with 100% in normal matched lung tissue. The expression was as strong as in normal tissue in only 19 cases. FHIT expression was significantly lower in squamous cell carcinoma (SCC) (5%) than in adenocarcinoma (ADC) (64%). The median expression of Ki-67 was 20% and 69% of tumours were positives (expression >10%). Ki-67 expression was significantly higher in SCC (33.3%) than in ADC (10%). The loss of FHIT protein was not correlated with the expression of p53 (median: 7.5%, 58% of positive tumours for a cut-off of 10% of positive cells) or Ki-67. But percentage of labelled cells for p53 and Ki-67 were significantly correlated. The results suggest that for fragile histidine triad, the pathway of tumourigenesis is independent of p53 and of tumoural proliferation, as reported previously in vitro.
authors.affiliation: Dept of Internal Medicine and Laboratory of Clinical Investigation and Experimental Oncology, Jules Bordet Institute, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Mascaux
authors.forename: B
authors.initials: B
authors.lastname: Martin
authors.forename: J M
authors.initials: JM
authors.lastname: Verdebout
authors.forename: A P
authors.initials: AP
authors.lastname: Meert
authors.forename: V
authors.initials: V
authors.lastname: Ninane
authors.forename: J P
authors.initials: JP
authors.lastname: Sculier
mesh_terms: D017766:Acid Anhydride Hydrolases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D000099170:Bis(5'-adenosyl)triphosphatase