Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location.

Détails

ID Serval
serval:BIB_14630D489A5C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location.
Périodique
Diseases of the colon and rectum
Auteur(s)
Gervaz P., Bouzourene H., Cerottini J.P., Chaubert P., Benhattar J., Secic M., Wexner S., Givel J.C., Belin B.
ISSN
0012-3706
Statut éditorial
Publié
Date de publication
2001
Peer-reviewed
Oui
Volume
44
Numéro
3
Pages
364-72; discussion 372-3
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
PURPOSE: The aim of this study was to determine whether tumor location proximal or distal to the splenic flexure is associated with distinct molecular patterns and can predict clinical outcome in a homogeneous group of patients with Dukes B (T3-T4, N0, M0) colorectal cancer. It has been hypothesized that proximal and distal colorectal cancer may arise through different pathogenetic mechanisms. Although p53 and Ki-ras gene mutations occur frequently in distal tumors, another form of genomic instability associated with defective DNA mismatch repair has been predominantly identified in the proximal colon. To date, however, the clinical usefulness of these molecular characteristics remains unproven. METHODS: A total of 126 patients with a lymph node-negative sporadic colon or rectum adenocarcinoma were prospectively assessed with the endpoint of death by cancer. No patient received either radiotherapy or chemotherapy. p53 protein was studied by immunohistochemistry using DO-7 monoclonal antibody, and p53 and Ki-ras gene mutations were detected by single strand conformation polymorphism assay. RESULTS: During a mean follow-up of 67 months, the overall five-year survival was 70 percent. Nuclear p53 staining was found in 57 tumors (47 percent), and was more frequent in distal than in proximal tumors (55 vs. 21 percent; chi-squared test, P < 0.001). For the whole group, p53 protein expression correlated with poor survival in univariate and multivariate analysis (log-rank test, P = 0.01; hazard ratio = 2.16; 95 percent confidence interval = 1.12-4.11, P = 0.02). Distal colon tumors and rectal tumors exhibited similar molecular patterns and showed no difference in clinical outcome. In comparison with distal colorectal cancer, proximal tumors were found to be statistically significantly different on the following factors: mucinous content (P = 0.008), degree of histologic differentiation (P = 0.012), p53 protein expression, and gene mutation (P = 0.001 and 0.01 respectively). Finally, patients with proximal tumors had a marginally better survival than those with distal colon or rectal cancers (log-rank test, P = 0.045). CONCLUSION: In this series of Dukes B colorectal cancers, p53 protein expression was an independent factor for survival, which also correlated with tumor location. Eighty-six percent of p53-positive tumors were located in the distal colon and rectum. Distal colon and rectum tumors had similar molecular and clinical characteristics. In contrast, proximal neoplasms seem to represent a distinct entity, with specific histopathologic characteristics, molecular patterns, and clinical outcome. Location of the neoplasm in reference to the splenic flexure should be considered before group stratification in future trials of adjuvant chemotherapy in patients with Dukes B tumors.
Mots-clé
Adenocarcinoma, Adult, Aged, Aged, 80 and over, Colon, Colorectal Neoplasms, DNA Mutational Analysis, Female, Humans, Male, Middle Aged, Neoplasm Staging, Polymorphism, Single-Stranded Conformational, Prospective Studies, Proto-Oncogene Proteins p21(ras), Rectum, Survival Rate, Tumor Suppressor Protein p53
Pubmed
Web of science
Création de la notice
28/01/2008 9:56
Dernière modification de la notice
20/08/2019 13:43
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