Prognostic value of TP53 and K-ras-2 mutational analysis in stage III carcinoma of the colon

Victor E. Pricolo, Sydney D. Finkelstein, Tsung T. Wu, Gerald Keller, Anke Bakker, Patricia A. Swalsky, Kirby I. Bland

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

BACKGROUND: Genetic mutations involving oncogenes and tumor-suppressor genes occur in carcinogenesis, and may effect biologic behavior of neoplasms. In this study, we analyzed the prognostic value of mutational analysis in colon carcinoma. PATIENTS AND METHODS: Archival pathology specimens from 70 consecutive patients, resected for stage III colon carcinoma, were analyzed for point mutations by amplification and direct sequencing of exons from the K-ras-2 and the TP53 genes (topographic genotyping). Mutations were compared with adverse histopathologic features (poor differentiation, vascular and lymphatic invasion, mucin production) as prognostic markers. RESULTS: Five- year survival was 75% in patients with nonmutated lesions, significantly lower (21%) with TP53 mutations (P = 0.01), and intermediate with K-ras-2 only (45%) or both K-ras-2 and TP53 mutations (36%). A TP53 mutation carried the highest relative risk of death (2.39; 95% confidence interval, 1.29 to 4.42; P = 0.006). There was an additive effect on the risk of death between TP53 mutations and adverse histopathologic features. CONCLUSIONS: The information derived from mutational analysis is creating new prognostic variables that may play a role in the choice of therapy for colorectal carcinoma.

Original languageEnglish (US)
Pages (from-to)41-46
Number of pages6
JournalAmerican Journal of Surgery
Volume171
Issue number1
DOIs
StatePublished - Jan 1996
Externally publishedYes

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Colon
Carcinoma
Mutation
p53 Genes
Mucins
Tumor Suppressor Genes
Oncogenes
Point Mutation
Blood Vessels
Colorectal Neoplasms
Exons
Carcinogenesis
Confidence Intervals
Pathology
Survival
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Surgery

Cite this

Pricolo, V. E., Finkelstein, S. D., Wu, T. T., Keller, G., Bakker, A., Swalsky, P. A., & Bland, K. I. (1996). Prognostic value of TP53 and K-ras-2 mutational analysis in stage III carcinoma of the colon. American Journal of Surgery, 171(1), 41-46. https://doi.org/10.1016/S0002-9610(99)80071-3

Prognostic value of TP53 and K-ras-2 mutational analysis in stage III carcinoma of the colon. / Pricolo, Victor E.; Finkelstein, Sydney D.; Wu, Tsung T.; Keller, Gerald; Bakker, Anke; Swalsky, Patricia A.; Bland, Kirby I.

In: American Journal of Surgery, Vol. 171, No. 1, 01.1996, p. 41-46.

Research output: Contribution to journalArticle

Pricolo, VE, Finkelstein, SD, Wu, TT, Keller, G, Bakker, A, Swalsky, PA & Bland, KI 1996, 'Prognostic value of TP53 and K-ras-2 mutational analysis in stage III carcinoma of the colon', American Journal of Surgery, vol. 171, no. 1, pp. 41-46. https://doi.org/10.1016/S0002-9610(99)80071-3
Pricolo, Victor E. ; Finkelstein, Sydney D. ; Wu, Tsung T. ; Keller, Gerald ; Bakker, Anke ; Swalsky, Patricia A. ; Bland, Kirby I. / Prognostic value of TP53 and K-ras-2 mutational analysis in stage III carcinoma of the colon. In: American Journal of Surgery. 1996 ; Vol. 171, No. 1. pp. 41-46.
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N2 - BACKGROUND: Genetic mutations involving oncogenes and tumor-suppressor genes occur in carcinogenesis, and may effect biologic behavior of neoplasms. In this study, we analyzed the prognostic value of mutational analysis in colon carcinoma. PATIENTS AND METHODS: Archival pathology specimens from 70 consecutive patients, resected for stage III colon carcinoma, were analyzed for point mutations by amplification and direct sequencing of exons from the K-ras-2 and the TP53 genes (topographic genotyping). Mutations were compared with adverse histopathologic features (poor differentiation, vascular and lymphatic invasion, mucin production) as prognostic markers. RESULTS: Five- year survival was 75% in patients with nonmutated lesions, significantly lower (21%) with TP53 mutations (P = 0.01), and intermediate with K-ras-2 only (45%) or both K-ras-2 and TP53 mutations (36%). A TP53 mutation carried the highest relative risk of death (2.39; 95% confidence interval, 1.29 to 4.42; P = 0.006). There was an additive effect on the risk of death between TP53 mutations and adverse histopathologic features. CONCLUSIONS: The information derived from mutational analysis is creating new prognostic variables that may play a role in the choice of therapy for colorectal carcinoma.

AB - BACKGROUND: Genetic mutations involving oncogenes and tumor-suppressor genes occur in carcinogenesis, and may effect biologic behavior of neoplasms. In this study, we analyzed the prognostic value of mutational analysis in colon carcinoma. PATIENTS AND METHODS: Archival pathology specimens from 70 consecutive patients, resected for stage III colon carcinoma, were analyzed for point mutations by amplification and direct sequencing of exons from the K-ras-2 and the TP53 genes (topographic genotyping). Mutations were compared with adverse histopathologic features (poor differentiation, vascular and lymphatic invasion, mucin production) as prognostic markers. RESULTS: Five- year survival was 75% in patients with nonmutated lesions, significantly lower (21%) with TP53 mutations (P = 0.01), and intermediate with K-ras-2 only (45%) or both K-ras-2 and TP53 mutations (36%). A TP53 mutation carried the highest relative risk of death (2.39; 95% confidence interval, 1.29 to 4.42; P = 0.006). There was an additive effect on the risk of death between TP53 mutations and adverse histopathologic features. CONCLUSIONS: The information derived from mutational analysis is creating new prognostic variables that may play a role in the choice of therapy for colorectal carcinoma.

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