Phenotypes of invasion in sporadic colorectal carcinomas related to aberrations of the adenomatous polyposis coli (APC ) gene.
OBJECTIVE
To determine whether the dissociation of tumour cells from neoplastic glands in colorectal carcinomas is caused by disruption of the wnt-signalling pathway and whether the adenomatous polyposis coli (APC) protein is implicated in this.


RESULTS
In a series of 99 clinically sporadic colorectal carcinomas, APC exon 15 mutations, loss of heterozygosity (LOH) and promoter methylation were found in 49, 20 and 23 cases, respectively. Singly, these APC aberrations were not associated with the degree of tumour cell dissociation, but dissociation was higher for the cases with combined APC mutation and LOH. Immunohistochemical beta-catenin translocation to the nucleus correlated with APC aberrations. Tumour growth pattern (expansive/infiltrative/diffuse) and tumour stroma (desmoplastic common-type versus keloid-like) showed a statistically significant association with tumour cell dissociation and with beta-catenin translocation. Of other molecular alterations tested (p53 mutation; LOH at 17p13, 18q, 9p21; CpG island methylator phenotype), only the highly microsatellite unstable status (n = 11) was negatively associated.


CONCLUSIONS
In colorectal carcinomas, wnt dysregulation relates to APC aberrations, but wnt dysregulation and APC aberrations are not strictly required for tumour cell dissociation, and additional and/or alternative factors must play a role. Of these, outside-in signalling by cancer cell-matrix interactions, as partially mirrored in histomorphological features, could be important.
Prall
F
F
Institute of Pathology, University of Rostock, Rostock, Germany. friedrich.prall@med.uni-rostock.de
Weirich
V
V
Ostwald
C
C
D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D017491:Genes, APC; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D014178:Translocation, Genetic; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D014408:Biomarkers, Tumor; D015820:Cadherins; D051153:Wnt Proteins; D051176:beta Catenin