Current status of adjuvant chemotherapy for colorectal cancer: Can molecular markers play a role in predicting prognosis?

M. J. O'Connell, Daniel J Schaid, V. Ganju, Julie M Cunningham, J. S. Kovach, Stephen N Thibodeau

Research output: Contribution to journalArticle

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Abstract

Background. Recent clinical trials establish a beneficial effect for adjuvant chemotherapy after surgical resection of the primary tumor (1) as single treatment for patients with colonic cancer and (2) combined with radiation therapy for patients with rectal cancer. Because adjuvant chemotherapy is not universally effective and is associated with toxicity and some degree of risk, it would be desirable to supplement standard pathologic staging criteria to define more precisely the subset of patients at high risk for tumor recurrence who would benefit most from adjuvant therapy. Tumor cell DNA content and cell proliferation measured by flow cytometry were identified as important and independent prognostic factors for patients undergoing curative resection of colorectal cancer. Basic laboratory investigations show a series of more specific molecular and genetic abnormalities that might provide better prognostic discrimination. Recent molecular studies suggest that the process of tumorigenesis in colorectal cancer proceeds through a series of genetic alterations that include both dominant and recessive protooncogenes. Characterization of these molecular genetic abnormalities may provide valuable prognostic information for use in patient management. Methods. Allelic loss was studied for chromosomes 5, 17, and 18, and immunohistochemical analysis was done of the p53 protein product in tumors from 91 patients with colorectal cancer. Results. Preliminary analysis of disease-free survival after surgical resection in 60 patients with Dukes' B or C tumors suggests a poorer prognosis associated with allelic loss on chromosome 18q (P = 0.08). Conclusions. Additional studies involving a much larger population of patients with Dukes' B and C colorectal cancer are needed to define the true prognostic significance of these molecular markers.

Original languageEnglish (US)
Pages (from-to)1732-1739
Number of pages8
JournalCancer
Volume70
Issue number6 SUPPL.
StatePublished - 1992

Fingerprint

Adjuvant Chemotherapy
Colorectal Neoplasms
Loss of Heterozygosity
Neoplasms
Molecular Biology
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 17
Rectal Neoplasms
Colonic Neoplasms
Disease-Free Survival
Flow Cytometry
Carcinogenesis
Radiotherapy
Chromosomes
Cell Proliferation
Clinical Trials
Recurrence
DNA
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Current status of adjuvant chemotherapy for colorectal cancer : Can molecular markers play a role in predicting prognosis? / O'Connell, M. J.; Schaid, Daniel J; Ganju, V.; Cunningham, Julie M; Kovach, J. S.; Thibodeau, Stephen N.

In: Cancer, Vol. 70, No. 6 SUPPL., 1992, p. 1732-1739.

Research output: Contribution to journalArticle

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abstract = "Background. Recent clinical trials establish a beneficial effect for adjuvant chemotherapy after surgical resection of the primary tumor (1) as single treatment for patients with colonic cancer and (2) combined with radiation therapy for patients with rectal cancer. Because adjuvant chemotherapy is not universally effective and is associated with toxicity and some degree of risk, it would be desirable to supplement standard pathologic staging criteria to define more precisely the subset of patients at high risk for tumor recurrence who would benefit most from adjuvant therapy. Tumor cell DNA content and cell proliferation measured by flow cytometry were identified as important and independent prognostic factors for patients undergoing curative resection of colorectal cancer. Basic laboratory investigations show a series of more specific molecular and genetic abnormalities that might provide better prognostic discrimination. Recent molecular studies suggest that the process of tumorigenesis in colorectal cancer proceeds through a series of genetic alterations that include both dominant and recessive protooncogenes. Characterization of these molecular genetic abnormalities may provide valuable prognostic information for use in patient management. Methods. Allelic loss was studied for chromosomes 5, 17, and 18, and immunohistochemical analysis was done of the p53 protein product in tumors from 91 patients with colorectal cancer. Results. Preliminary analysis of disease-free survival after surgical resection in 60 patients with Dukes' B or C tumors suggests a poorer prognosis associated with allelic loss on chromosome 18q (P = 0.08). Conclusions. Additional studies involving a much larger population of patients with Dukes' B and C colorectal cancer are needed to define the true prognostic significance of these molecular markers.",
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T2 - Can molecular markers play a role in predicting prognosis?

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AU - Kovach, J. S.

AU - Thibodeau, Stephen N

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N2 - Background. Recent clinical trials establish a beneficial effect for adjuvant chemotherapy after surgical resection of the primary tumor (1) as single treatment for patients with colonic cancer and (2) combined with radiation therapy for patients with rectal cancer. Because adjuvant chemotherapy is not universally effective and is associated with toxicity and some degree of risk, it would be desirable to supplement standard pathologic staging criteria to define more precisely the subset of patients at high risk for tumor recurrence who would benefit most from adjuvant therapy. Tumor cell DNA content and cell proliferation measured by flow cytometry were identified as important and independent prognostic factors for patients undergoing curative resection of colorectal cancer. Basic laboratory investigations show a series of more specific molecular and genetic abnormalities that might provide better prognostic discrimination. Recent molecular studies suggest that the process of tumorigenesis in colorectal cancer proceeds through a series of genetic alterations that include both dominant and recessive protooncogenes. Characterization of these molecular genetic abnormalities may provide valuable prognostic information for use in patient management. Methods. Allelic loss was studied for chromosomes 5, 17, and 18, and immunohistochemical analysis was done of the p53 protein product in tumors from 91 patients with colorectal cancer. Results. Preliminary analysis of disease-free survival after surgical resection in 60 patients with Dukes' B or C tumors suggests a poorer prognosis associated with allelic loss on chromosome 18q (P = 0.08). Conclusions. Additional studies involving a much larger population of patients with Dukes' B and C colorectal cancer are needed to define the true prognostic significance of these molecular markers.

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