Fas ligand is up-regulated during the colorectal adenoma-carcinoma sequence.
OBJECTIVE
Fas ligand (FasL) expression by cancer cells may mediate tumour immune privilege. The purpose of the present study was to investigate the timing and significance of FasL expression during the colorectal adenoma-carcinoma sequence.


METHODS
FasL expression was studied by immunohistochemistry in 170 formalin-fixed tissue sections representing the entire colorectal adenoma-carcinoma sequence. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to search for FasL mRNA. Analysis of survival was performed in patients with carcinomas.


RESULTS
A significant positive linear correlation was found between FasL expression and tumour progression throughout the colorectal adenoma-carcinoma sequence (r(s)=0.677 P<0.001). A pattern of high FasL expression was detected in 19% of high grade adenomas, 40% of stage I-II, 67% of stage III and 70% of stage IV carcinomas. No significant differences were observed between FasL expression in the primary tumours and that in the corresponding liver metastases. The specificity of FasL expression was confirmed at RT-PCR. For stage I-II carcinomas, the 5 year survival was 90% in patients without, or with moderate, tumoural FasL expression compared with 60% in those with high tumoural FasL expression (P<0.05).


CONCLUSIONS
Our findings suggest that FasL expression may be involved in the development of colorectal cancer and its progression.
Belluco
C
C
Division of Surgery, Department of Oncological and Surgical Sciences, Padova, Italy. claudio.belluco@unipd.it
Esposito
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Bertorelle
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Alaggio
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Giacomelli
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Bianchi
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LC
Nitti
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Lise
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D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000473:pathology*; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins