Colorectal carcinoma patients from hereditary non-polyposis colorectal cancer families are suggested to have a better prognosis than sporadic colorectal carcinoma cases. Since the majority of hereditary non-polyposis colorectal cancer-related colorectal carcinomas are characterized by microsatellite instability due to germline mutations in DNA mismatch repair genes, this is consistent with the prolonged survival observed in sporadic microsatellite instability-positive colorectal carcinoma compared to microsatellite stable cases. However, a fraction of colorectal carcinoma cases belongs to families that, despite fulfilling the clinical criteria for hereditary non-polyposis colorectal cancer, do not carry mismatch repair gene mutations. Our aim was to verify to what extent the genotypic heterogeneity influences the prognosis of hereditary non-polyposis colorectal cancer patients.A survival analysis was performed on 526 colorectal carcinoma cases from 204 Amsterdam Criteria-positive hereditary non-polyposis colorectal cancer families. Enrolled cases were classified as MLH1-positive, MSH2-positive and mutation-negative, according to the results of genetic testing in each family.Five-year survival rates were 0.73 (95\% CI, 0.66-0.80), 0.75 (95\% CI, 0.66-0.84) and 0.62 (95\% CI, 0.55-0.68) for MLH1-positive, MSH2-positive and mutation-negative groups, respectively (logrank test, P = 0.01). Hazard ratio, computed using Cox regression analysis and adjusted for age, sex, tumor site and stage, was 0.71 (95\% CI, 0.51-0.98) for the mutation-positive compared to the mutation-negative group. Moreover, in the latter group, patients with microsatellite instability-positive colorectal carcinomas showed a better outcome than microsatellite stable cases (5-year survival rates, 0.81 and 0.60, respectively; logrank test, P = 0.006).Our results suggest that the prognosis of hereditary non-polyposis colorectal cancer-related colorectal carcinoma patients depends on the associated constitutional mismatch repair genotype.

Prognostic relevance of MLH1 and MSH2 mutations in hereditary non-polyposis colorectal cancer patients / A. Russo;P. Sala;P. Alberici;I. Gazzoli;P. Radice;C. Montefusco;M. Torrini;C. Mareni;M. Fornasarig;M. Santarosa;A. Viel;P. Benatti;M. Pedroni;M. Pedroni;M. P. de;E. Lucci-Cordisco;M. Genuardi;L. Messerini;V. Stigliano;A. Cama;M. C. Curia;L. d. Lellis;S. Signoroni;M. A. Pierotti;L. Bertario. - In: TUMORI. - ISSN 0300-8916. - STAMPA. - 95:(2009), pp. 731-738.

Prognostic relevance of MLH1 and MSH2 mutations in hereditary non-polyposis colorectal cancer patients.

GENUARDI, MAURIZIO;MESSERINI, LUCA;
2009

Abstract

Colorectal carcinoma patients from hereditary non-polyposis colorectal cancer families are suggested to have a better prognosis than sporadic colorectal carcinoma cases. Since the majority of hereditary non-polyposis colorectal cancer-related colorectal carcinomas are characterized by microsatellite instability due to germline mutations in DNA mismatch repair genes, this is consistent with the prolonged survival observed in sporadic microsatellite instability-positive colorectal carcinoma compared to microsatellite stable cases. However, a fraction of colorectal carcinoma cases belongs to families that, despite fulfilling the clinical criteria for hereditary non-polyposis colorectal cancer, do not carry mismatch repair gene mutations. Our aim was to verify to what extent the genotypic heterogeneity influences the prognosis of hereditary non-polyposis colorectal cancer patients.A survival analysis was performed on 526 colorectal carcinoma cases from 204 Amsterdam Criteria-positive hereditary non-polyposis colorectal cancer families. Enrolled cases were classified as MLH1-positive, MSH2-positive and mutation-negative, according to the results of genetic testing in each family.Five-year survival rates were 0.73 (95\% CI, 0.66-0.80), 0.75 (95\% CI, 0.66-0.84) and 0.62 (95\% CI, 0.55-0.68) for MLH1-positive, MSH2-positive and mutation-negative groups, respectively (logrank test, P = 0.01). Hazard ratio, computed using Cox regression analysis and adjusted for age, sex, tumor site and stage, was 0.71 (95\% CI, 0.51-0.98) for the mutation-positive compared to the mutation-negative group. Moreover, in the latter group, patients with microsatellite instability-positive colorectal carcinomas showed a better outcome than microsatellite stable cases (5-year survival rates, 0.81 and 0.60, respectively; logrank test, P = 0.006).Our results suggest that the prognosis of hereditary non-polyposis colorectal cancer-related colorectal carcinoma patients depends on the associated constitutional mismatch repair genotype.
2009
95
731
738
A. Russo;P. Sala;P. Alberici;I. Gazzoli;P. Radice;C. Montefusco;M. Torrini;C. Mareni;M. Fornasarig;M. Santarosa;A. Viel;P. Benatti;M. Pedroni;M. Pedroni;M. P. de;E. Lucci-Cordisco;M. Genuardi;L. Messerini;V. Stigliano;A. Cama;M. C. Curia;L. d. Lellis;S. Signoroni;M. A. Pierotti;L. Bertario
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/650667
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