Cancer risk assessment in long-standing pouchitis. DNA aberrations are rare in transformed neoplastic pelvic pouch mucosa.
BACKGROUND
In a small subgroup of patients with ulcerative colitis (UC) undergoing proctocolectomy and restorative ileal pouch-anal anastomosis (IPAA), a colonic-like pouch mucosa with severe and persistent villous atrophy (type C pattern) develops. Neoplastic transformation of the mucosa in the neorectum may occur in these patients. We hypothesized that genetic alterations associated with colorectal carcinoma (CRC) could be an early finding in this transformational process and thus potentially useful as clinical monitors in carcinoma risk assessment.


METHODS
In six patients with long-standing severe pouchitis and a type C-pattern mucosa, biopsies were obtained from five different locations of the pouches. DNA was PCR-amplified and analyzed by automated fragment analysis for loss of heterozygosity (LOH) at chromosome 5q14-22, 17p12-13, and 18q12-22. Point mutations of the K-ras and adenomatous polyposis coli (APC) genes were studied by sequencing.


RESULTS
The patients had varying degrees of dysplasia and one displayed DNA aneuploidy. Loss of heterozygosity at 5q15-22 was detected in three of five biopsies in one patient. This particular patient had no signs of dysplasia or DNA aneuploidy and a normal exon 15 sequence of the APC gene. No alterations of either the K-ras or the APC genes or LOH of 5q, 17p, or 18q were seen in any of the other patients.


CONCLUSIONS
Dysplasia, aneuploidy, and LOH in 5q may all reflect different parts of an atrophic mucosa-dysplasia-carcinoma sequence, in line with current concepts of carcinogenesis for CRC in long-standing pouchitis. Further studies of histological and molecular events in IPAA patients with severe atrophy are warranted.
Gullberg
Kjell
K
Department of Surgery, Karolinska Institute, Huddinge University Hospital, Sweden.
Lindforss
Ulrik
U
Zetterquist
Henrik
H
Stålberg
Dagny
D
Reinholt
Finn P
FP
Veress
Bela
B
Tribukait
Berhard
B
Olivecrona
Hans
H
Löfberg
Robert
R
D000328:Adult; D000782:Aneuploidy; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D002648:Child; D003093:Colitis, Ulcerative / Q000601:surgery; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics; D004247:DNA / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D017491:Genes, APC; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D019449:Pouchitis / Q000150:complications / Q000235:genetics / Q000473:pathology*; D012307:Risk Factors
D004273:DNA, Neoplasm; D004247:DNA