Analysis of allelic imbalance in patients with colorectal cancer according to stage and presence of synchronous liver metastases.
OBJECTIVE
To investigate the relationship between number and location of allelic imbalances (AI) and local tumor progression according to Astler-Coller classification.


BACKGROUND
Spontaneous errors in DNA replication (i.e., allelic imbalance or microsatellite instability) have been suggested to play an important role in carcinomatous transformation as reflecting alterations of gene function.


METHODS
One hundred two consecutive patients with colorectal carcinoma undergoing surgical resection were included in this study. Patients were distributed according to the Astler-Coller classification as stages A (n = 7), B1 (n = 15), B2 (n = 24), C (n = 31), and D (n = 25). Fluorescent polymerase chain reaction was performed on frozen tumor, normal colon mucosa, and blood DNA at 35 microsatellite markers. Allelic imbalance frequency was compared with tumor staging.


RESULTS
The percentage of AI was significantly higher in stage D than in A/B1 and B2. In addition, the percentage of AI was significantly higher in 10 synchronous colorectal liver metastases than in stage A/B1 and B2 tumors. However, the allelotyping revealed a subgroup of A/B1 tumors with a high AI frequency. Statistical analysis showed that the presence of AI at microsatellites D1S305, D2S138, D3S1282, D17S790, and D22S928 presented a significantly positive correlation with stages.


CONCLUSIONS
The frequency of AI significantly correlates with tumor progression of colorectal cancer. Primary tumors with synchronous colorectal liver metastases showed a higher percentage of AI, suggesting that a frequency of AI greater than 35% with this selection of markers indicates a high risk of local progression and of development of metastases.
Weber
J C
JC
Centre de Chirurgie Viscérale et de Transplantation, Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, 67098 Strasbourg Cedex, France.
Schneider
A
A
Rohr
S
S
Nakano
H
H
Bachellier
P
P
Méchine
A
A
Hamel
G
G
Kanor
M
M
Chenard
M P
MP
Gaub
M P
MP
Oudet
P
P
Meyer
C
C
Jaeck
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis