Piotr Hadaczek(1), Tadeusz Debniak(1), Grzegorz Kurzawski(1), Anna Jakubowska(1), Tomasz Huzarski(1), Kay Huebner(2), Jan Lubinski(1)

Fhit Protein Expression in Hereditary and Sporadic Colorectal Cancers

1) Department of Genetics and Pathology, Pomeranian Academy of Medicine, Szczecin,
2) Department of Microbiology and Immunology, Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, Pennsylvania, USA

Abstract

The majority of hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in DNA mismatch repair genes, especially in MLH1 and MSH2. Tumours in such patients also show microsatellite instability characteristic for DNA repair defects. The FHIT gene, a candidate tumour suppressor gene located at 3p14.2 has been shown to be involved in carcinogenesis of many human tissues, including digestive tract tissues. In our study, we characterized Fhit protein expression in hereditary and sporadic colorectal cancers (CRC). Our intention was to determine if cancers with mutations in the mismatch repair genes, MSH2 and MLH1, would show more frequent inactivation of the FHIT gene. Sixteen HNPCC and 28 sporadic CRC cases were examined by standard immunohistochemical analyses. Both study groups comprised carefully and selectively chosen cases. We have observed higher frequency of loss or reduction of Fhit protein expression in hereditary CRC than in sporadic cases (44% vs. 25%). Although this difference was not statistically significant (p=0.17), possibly due to the small number of available tumour specimens, the tendency is interesting. More extensive studies on a larger number of cases should be done in the HNPCC group to confirm statistical significance. Our results suggest that the FHIT gene plays an important role in carcinogenesis of at least one fourth of all colorectal cancers.