Expression of FHIT (quick score 98.7 vs. 206.4) and p27 (QS 187.3 vs. 244.8) was significantly lower in carcinomas compared to non-tumor control tissue.
The mean number of TRGs (<i>FHIT, E-cadherin, MLH1</i>/<i>MSH2</i>, and <i>COX-2</i>) that exhibited reduced or absent expression in LGIN, HGIN/CIS and invasive cancer specimens was 1.12±0.61, 1.66±0.93 and 2.09±0.96, respectively, demonstrating a significant stepwise increment from LGIN to HGIN/CIS and then to invasive cancer (P<0.05). p53 overexpression was frequently detected in ESN with head and neck carcinomas.
Our results suggest that hypermethylation of the FHIT 5'CpG island may be responsible for inactivation of the FHIT gene in clear cell renal carcinomas.
The FHIT gene encompassing the most active common human fragile region, FRA3B, has been proposed as a tumour suppressor gene for important common human carcinomas.
The fragile histidine triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in a variety of tumours, including gastric carcinomas.
The fragile histidine triad (FHIT) gene is a candidate tumor suppressor gene located at 3p14.2, and the absence or reduction of Fhit protein expression has recently been reported in various carcinomas.
In this study we investigated FHIT (Fragile Histidine Triad) protein alterations in cervical carcinomas to assess the relation of this gene with cervical cancer.
Loss of expression of the Fhit protein is often associated with the development of many human epithelial cancers, including lung and cervical carcinomas.
Aberration of FHIT gene is associated with increased tumor proliferation and decreased apoptosis-clinical evidence in lung and head and neck carcinomas.
Genomic alterations and abnormal expression of the fragile histidine triad (FHIT) gene in gastric carcinomas were examined to determine whether the FHIT gene is actually a frequent target for alteration during gastric carcinogenesis.
The present study of 67 NSCLCs investigated the allelic imbalance (AIm) within the FHIT locus and its relationship with p53 abnormalities, kinetic parameters [proliferative activity or proliferation index (PI) and apoptotic index (AI)], and ploidy status of the carcinomas.
Loss or impaired expression of the fhit-gene product was detected in 13 of 30 (43%) cervical carcinomas by immunohistochemistry, whereas all 6 normal cervical epithelia, or 22 CINs, expressed fhit protein.
The results confirm that Fhit protein expression is reduced or absent in the majority of cervical carcinomas and suggest that loss of Fhit expression often accompanies cervical tumor progression.
In contrast, FHIT alterations were found in the three RER(+) pancreatic carcinomas screened; two had FHIT homozygous deletions affecting exon 5 and the third had a heterozygous missense mutation (H76N).
We evaluated FHIT gene involvement in 39 esophageal carcinomas (18 adenocarcinomas [AC¿, 21 squamous cell carcinomas [SCC]) by both reverse transcriptase-polymerase chain reaction (RT-PCR) amplification and loss of heterozygosity analysis (LOH).
These findings suggest that LOH of the FHIT gene represents an event in the tumourigenesis of only a small subset of gastric carcinomas and does not correlate with tumour progression or prognosis.
These data indicate that the aberrant expression of the FHIT gene is observed in precursor lesions of cervical carcinoma as well as invasive carcinomas, with its incidence not increasing with advance of clinical stage.
In the group of non-smoking subjects p53 mutations and LOH at the FHIT locus were present in seven (20%) cases, and the two alterations were constantly associated (P < 0.0001), whereas they were not related in the series of carcinomas caused by smoking.
However, evidence continues to accumulate, demonstrating that FHIT inactivation occurs in the majority of lung, gastric, cervical, and kidney carcinomas and that replacement of Fhit expression in such cancer cells suppresses their tumorigenicity.