TY - JOUR
T1 - Prognostic value of TP53 and K-ras-2 mutational analysis in stage III carcinoma of the colon
AU - Pricolo, Victor E.
AU - Finkelstein, Sydney D.
AU - Wu, Tsung Teh
AU - Keller, Gerald
AU - Bakker, Anke
AU - Swalsky, Patricia A.
AU - Bland, Kirby I.
PY - 1996/1
Y1 - 1996/1
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.
UR - http://www.scopus.com/inward/record.url?scp=0030043831&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030043831&partnerID=8YFLogxK
U2 - 10.1016/S0002-9610(99)80071-3
DO - 10.1016/S0002-9610(99)80071-3
M3 - Article
C2 - 8554149
AN - SCOPUS:0030043831
SN - 0002-9610
VL - 171
SP - 41
EP - 46
JO - American journal of surgery
JF - American journal of surgery
IS - 1
ER -