Fragile histidine triad (FHIT) gene is overexpressed in colorectal cancer.
OBJECTIVE
FHIT gene, mapped at FRA3B site, encodes human diadenosine triphosphate hydrolase involved in the regulation of cell cycle and nucleotide metabolism. Decreased FHIT gene expression was previously observed in various types of human cancer, however, quantification of FHIT mRNA was seldom performed.


OBJECTIVE
To investigate loss of heterozygosity (LOH) at FRA3B, expression of FHIT gene at the mRNA and protein levels in sporadic colorectal carcinoma (CRC) and benign colon adenoma.


METHODS
FHIT mRNA was quantified by the validated realtime PCR (QPCR) in tumor samples of 84 CRC patients and mucosal biopsies of 15 adenomas, in comparison to 37 control patients, whereas subgroup of 57 CRC, 10 adenoma and 10 control cases were selected for immunohistochemical (IHC) detection of the native FHIT protein and LOH determination at FRA3B.


RESULTS
Higher level of FHIT mRNA was found in 86% of CRC (P<0.001) and 60% of adenomas (P=0.016). IHC showed comparable results to QPCR (P=0.003), revealing the strongest presence of FHIT protein in Dukes' C/D stages (P<0.001) and N1/N2 lymph nodes metastasis in CRC (P=0.04). FHIT gene expression and Dukes' and G staging were positively correlated in CRC as analyzed by QPCR and IHC. Deletion analysis of the fragile FRA3B site revealed the highest LOH frequency at D3S1234 in 32.5% of CRC informative cases, however, LOH did not correspond to QPCR, IHC or clinical-pathological variables.


CONCLUSIONS
Our data suggest that reduction or absence of the FHIT gene expression is not a prerequisite for colorectal cancer development and progression.
Wierzbicki
P M
PM
Department of Histology, Medical University of Gdansk, Gdansk, Poland. pwierzb@amg.gda.pl
Adrych
K
K
Kartanowicz
D
D
Dobrowolski
S
S
Stanislawowski
M
M
Chybicki
J
J
Godlewski
J
J
Korybalski
B
B
Smoczynski
M
M
Kmiec
Z
Z
D017766:Acid Anhydride Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011044:Poland; D011446:Prospective Studies; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D017931:DNA Primers; D009363:Neoplasm Proteins; D012313:RNA; D012333:RNA, Messenger; D000099170:Bis(5'-adenosyl)triphosphatase