Analysis of allelic imbalance in patients with colorectal cancer accordingto stage and presence of synchronous liver metastases

Objective To investigate the relationship between number and location of al lelic imbalances (Al) and local tumor progression according to Astler-Colle r classification. Summary Background Data Spontaneous errors in DNA replication (i.e., alleli c imbalance or microsatellite instability) have been suggested to play an i mportant role in carcinomatous transformation as reflecting alterations of gene function. Methods One hundred two consecutive patients with colorectal carcinoma unde rgoing surgical resection were included in this study. Patients were distri buted 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 bloo d DNA at 35 microsatellite markers. Allelic imbalance frequency was compare d with tumor staging. Results The percentage of Al was significantly higher in stage D than in A/ B1 and B2. In addition, the percentage of Al 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 Al frequency. Statistical analysis showed that the presence of Al at microsat ellites D1S305, D2S138, D3S1282, D17S790, and D22S928 presented a significa ntly positive correlation with stages. Conclusion The frequency of Al significantly correlates with tumor progress ion of colorectal cancer. Primary tumors with synchronous colorectal liver metastases showed a higher percentage of Al, suggesting that a frequency of Al greater than 35% with this selection of markers indicates a high risk o f local progression and of development of metastases.