Genetic and protein markers related to in situ growth and multiplicity in small sporadic colorectal adenomas.
BACKGROUND
Some early genetic events in the development of colorectal adenomas are known, but their relationship to in vivo growth characteristics is uncertain. This study compared in situ size changes and other clinicopathological variables with selected genetic and protein markers.


METHODS
56 adenomas (< or = 10 mm) from 39 patients were analysed for APC, CTNNB1 and K-ras mutations, allelic imbalance on 1p and 18q, microsatellite instability and immunohistochemical expression of HLA-DR, BAX, BCL-2 and Ki-67. For 42 of the adenomas, in situ growth was measured over 3 years. The total number of polyps in each patient was recorded.


RESULTS
K-ras was mutated in 8/56 adenomas. None of the regressing adenomas revealed such mutations, compared to 20% in those that maintained or increased their size. Multivariate linear regression analysis showed that tumour growth was higher in females compared to males, and was even higher in the presence of a K-ras mutation. APC mutations were found in 37/56 adenomas. CTNNB1 mutations were found in 2/19 adenomas without APC mutation. Deletions of 1p were found in 12/56 adenomas and, seemingly, most frequent in patients with few tumours. The most frequently expressed protein was BAX (33/41), but neither this nor the other proteins showed associations with an in situ growth pattern.


CONCLUSIONS
The multivariate linear regression model showed that patient gender and the presence of K-ras mutation had significant effects on tumour growth. The lack of the proliferative stimulus resulting from a K-ras mutation may contribute to the process of adenoma regression.
Institute of Forensic Medicine, University of Oslo, The National Hospital, NO-0027 Oslo, Norway. tone.lovig@labmed.uio.no
T
T
Løvig
L
L
Thorstensen
B
B
Hofstad
S Norheim
SN
Andersen
O P Fraas
OP
Clausen
M
M
Vatn
R A
RA
Lothe
T O
TO
Rognum
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D018256:Adenomatous Polyps / Q000235:genetics*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D017354:Point Mutation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012737:Sex Factors; D013223:Statistics as Topic; D015534:Trans-Activators / Q000235:genetics; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051176:beta Catenin