OBJECTIVE: To investigate the relationship between number and location of allelic imbalances (AI) and local tumor progression according to Astler-Coller classification. SUMMARY BACKGROUND DATA: 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. CONCLUSION: 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.
OBJECTIVE: To investigate the relationship between number and location of allelic imbalances (AI) and local tumor progression according to Astler-Coller classification. SUMMARY BACKGROUND DATA: 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 B2tumors. 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. CONCLUSION: 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.
Authors: S Olschwang; R Hamelin; P Laurent-Puig; B Thuille; Y De Rycke; Y J Li; F Muzeau; J Girodet; R J Salmon; G Thomas Journal: Proc Natl Acad Sci U S A Date: 1997-10-28 Impact factor: 11.205
Authors: J R Lukish; K Muro; J DeNobile; R Katz; J Williams; D F Cruess; W Drucker; I Kirsch; S R Hamilton Journal: Ann Surg Date: 1998-01 Impact factor: 12.969
Authors: C R Boland; S N Thibodeau; S R Hamilton; D Sidransky; J R Eshleman; R W Burt; S J Meltzer; M A Rodriguez-Bigas; R Fodde; G N Ranzani; S Srivastava Journal: Cancer Res Date: 1998-11-15 Impact factor: 12.701
Authors: G Bardi; L A Parada; L Bomme; N Pandis; R Willén; B Johansson; B Jeppsson; K Beroukas; S Heim; F Mitelman Journal: Br J Cancer Date: 1997 Impact factor: 7.640