Tumor karyotype predicts clinical outcome in colorectal cancer patients
Acquired abnormalities of the genome in somatic cells may cause them to escape normal growth control and begin unchecked proliferation to give rise to malignant tumors. Many of the said abnormalities are visible microscopically as chromosomal aberrations during cell division. Different cancers carry different types of chromosome aberrations, enabling us to make precise diagnoses cancers based on cytogenetic analysis of tumor cells. Knowledge about these chromosomal abnormalities provides direct information about the genetic mechanisms through which the tumor arose, and this pathogenetic classification of tumors may to some extent differ from the morphological classification scheme. It has furthermore been shown that the chromosomal constitution of the tumor, its karyotype, may be an independent prognostisk parameter, both because it reveals something about the inherent aggressiveness of the disease cells and because it may show covariation with the response to treatment.
For 15 years we have collaborated with researchers from Denmark, Sweden, and Greece towards a chromosomal classification of large bowel tumors. We have established both the karyotypic differences between malignant and benign large bowel tumors and among the various types of colon and rectum carcinomas. For a group of 150 tumors examined cytogenetically after they had been removed surgically between 1989 and 1997, we have correlated the cytogenetic findings with 5-year survival and a variety of other clinico-pathologic parameters. It turned out that especially abnormalities affecting chromosomes 8 and 16 were associated with shorter survival after surgery, in addition to tumor grade and stage. When all prognostic variables were assessed together in a multivariate analysis, it could be shown that the type and number of acquired chromosome aberrations, and especially loss of chromosome 18, were independent prognostic variables for the total group of patients. For the subset of patients with stage I or II cancer, the very finding of structural chromosomal rearrangements predicted a poor prognosis, something the remaining clinico-pathologic parameters could not do equally well. In the subgroup of patients with stage III cancer, finally, structural rearrangements of chromosome 8 were more strongly correlated with poor prognosis than was tumor grade.
Conclusion: Whether chromosome abnormalities are detected at all and which abnormalities are detected in tumor cells cultured from patients with cancer of the large bowel is a strong predictor of disease outcome, even in the face of optimal surgical and oncological treatment. One should give serious thought to the possibility of merging information of this kind with other data to provide an as good as possible platform from which clinical decisions, including therapeutic choices, can be made, especially for patients whose disease is in the early or intermediary stages I, II, and III.
Article: Bardi G, Fenger C, Johansson B, Mitelman F, Heim S (2004): Tumor karyotype predicts clinical outcome in colorectal cancer patients. J Clin Oncol 22(13):2623-2634.
For 15 years we have collaborated with researchers from Denmark, Sweden, and Greece towards a chromosomal classification of large bowel tumors. We have established both the karyotypic differences between malignant and benign large bowel tumors and among the various types of colon and rectum carcinomas. For a group of 150 tumors examined cytogenetically after they had been removed surgically between 1989 and 1997, we have correlated the cytogenetic findings with 5-year survival and a variety of other clinico-pathologic parameters. It turned out that especially abnormalities affecting chromosomes 8 and 16 were associated with shorter survival after surgery, in addition to tumor grade and stage. When all prognostic variables were assessed together in a multivariate analysis, it could be shown that the type and number of acquired chromosome aberrations, and especially loss of chromosome 18, were independent prognostic variables for the total group of patients. For the subset of patients with stage I or II cancer, the very finding of structural chromosomal rearrangements predicted a poor prognosis, something the remaining clinico-pathologic parameters could not do equally well. In the subgroup of patients with stage III cancer, finally, structural rearrangements of chromosome 8 were more strongly correlated with poor prognosis than was tumor grade.
Conclusion: Whether chromosome abnormalities are detected at all and which abnormalities are detected in tumor cells cultured from patients with cancer of the large bowel is a strong predictor of disease outcome, even in the face of optimal surgical and oncological treatment. One should give serious thought to the possibility of merging information of this kind with other data to provide an as good as possible platform from which clinical decisions, including therapeutic choices, can be made, especially for patients whose disease is in the early or intermediary stages I, II, and III.
Article: Bardi G, Fenger C, Johansson B, Mitelman F, Heim S (2004): Tumor karyotype predicts clinical outcome in colorectal cancer patients. J Clin Oncol 22(13):2623-2634.