Ulcerative colitis and colorectal carcinoma: DNA-profile, laminin-5 gamma2 chain and cyclin A expression as early markers for risk assessment.
BACKGROUND
Ulcerative colitis patients are at increased risk for developing colorectal carcinomas. Despite expensive surveillance programmes, clinical practice reflects an uncertainty in individual risk assessment. The aim of the study was to evaluate independent cellular features with possible predictive value.


METHODS
Two patient groups were selected: group A comprised 8 patients with ulcerative colitis-associated colorectal carcinomas, group B comprised 16 ulcerative colitis patients with risk factors (duration of disease, extent of inflammation, epithelial dysplasias). A total of 683 paraffin-embedded mucosal biopsies were retrospectively evaluated for inflammatory activity, grade of dysplasia, ploidy status, laminin-5 gamma2 chain and cyclin A expression.


RESULTS
Mild or moderate inflammatory activity was present in 78% of all biopsies, low- or high-grade dysplasia in 5.5%. There was no difference in inflammatory activity and dysplasia between patient groups. In group A, 75% of the biopsies exhibited aneuploid DNA distribution patterns. Group B showed mainly proliferative-diploid cell populations (85% / P = 0.006). Laminin-5 gamma2 chain was expressed in 13% of all biopsies, with a higher frequency in group A (P = 0.002). Cyclin A expression was found in 98% of all biopsies, with a higher number of immunopositive cells in group A biopsies (P = 0.014).


CONCLUSIONS
Combined nuclear DNA assessment, laminin-5 gamma2 chain and cyclin A expression may help to identify ulcerative colitis patients with an increased risk for cancer development.
Habermann
J
J
Dept. of Oncology and Pathology, Karolinska Hospital, Stockholm, Sweden.
Lenander
C
C
Roblick
U J
UJ
Krüger
S
S
Ludwig
D
D
Alaiya
A
A
Freitag
S
S
Dümbgen
L
L
Bruch
H P
HP
Stange
E
E
Salo
S
S
Tryggvason
K
K
Auer
G
G
Schimmelpenning
H
H
D000328:Adult; D000368:Aged; D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D003093:Colitis, Ulcerative / Q000145:classification / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology*; D019925:Cyclin A / Q000032:analysis* / Q000235:genetics*; D004247:DNA / Q000032:analysis* / Q000235:genetics*; D016172:DNA Fingerprinting; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D000097794:Kalinin
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D019925:Cyclin A; D004247:DNA; D000097794:Kalinin