Summary:
Purpose
The investigation of the role of the receptor FxR with that of the oncogenes
k-ras, c-myc and telomerase (h-tert) in colorectal cancer at a protein
level,and their relationship of expression with different clinicopathological
parameters (gender, age, grade, stage, tumour location and diameter).
Methods
For the purposes of the study we used sixty (n=60) formalin-fixed and
paraffin-embedded tissue samples of colorectal adeno¬carcinoma obtained by
surgical resection, local or distant colectomies. The construction of tissue
microarrays was accomplished using ATA-100 apparatus forming three paraffin
blocks embedded with the whole 60 cases(1,5mm diameter tissue cylindrical
cores). Followed up by microtome sectioning and hematoxylin and eosin( H&E)
staining of the final blocks. Immunochemistry was performed using anti- FxR,
anti-htert, anti-cmyc and anti-kras antibodies. Digital image analysis was used
for the farnesoid X receptor,the oncogenes c-myc, k-ras and the molecule htert.
Statistical analysis of the data was performed by applying the Spss v 20
statistical software.
Results
Evaluation confirmed, strong associations between FxR and c-myc (p=0,01),
c-myc and the grade of differentiation of the examined neoplasms (p=0,021)
c-myc with k-ras (p=0,026), c-myc with telomerase (p=0,001), k-ras with
telomerase (p=0,025), FxR and age (p=0,022), h-tert and the diameter of the
neoplasm (p=0,039) It seems there is no association of FxR with telomerase and
k-ras.
Conclusions
The present study is the first that correlates the low expression of FXR with
the carcinogenetic mechanisms in human tissues(colon).It was confirmed that
low expression of FxR is obvious in the majority of the cases of colon cancer
which were examined 53/60 (88,3%),possibly meaning that there is a direct
association of the low expression of FxR and the development of colorectal
cancer. Strong association was confirmed for the first time in human tissue
between FxR and c-myc.Also association between c-myc and the grade of
differentiation of the examined neoplasms . Therefore there are other
unexplored pathways by which the association of FxR and c-myc are related with
the general destabilization of the cell cycle. Probably the targeted activation
of FxR in the early stages may have a preventive effect on colon cancer , thus
having a further therapeutic option for colon adenocarcinoma.
Keywords:
C-myc, Colon carcinoma, Fxr, K-ras, Telomerase
