OBJECTIVE: Colon cancers with high frequency microsatellite instability (MSI-H) are preferentially located in the proximal colon. Given that 15-20% of sporadic colon cancers are MSI-H, we determined whether tumor site-specific differences in clinicopathological variables, biomarkers, and prognosis are due to inclusion of MSI-H cases. METHODS: TNM stage II and III primary colon carcinomas (N = 528) from patients enrolled in 5-fluorouracil-based adjuvant trials were analyzed for MSI using 11 microsatellite markers. Immunostaining for DNA mismatch repair (hMLH1, hMSH2, hMSH6) and p53 proteins was performed. DNA ploidy (diploid vs aneuploid/tetraploid) and proliferative indices (PI: S-phase + G(2)M) were analyzed by flow cytometry. RESULTS: MSI-H was found in 95 (18%) colon cancers. Proximal tumors (N = 286) were associated with MSI-H, older age (>65 yr), poor differentiation, and diploid DNA content compared with distal tumors (all P< or = 0.016). Nuclear p53 staining was more frequent in distal tumors (P= 0.002); PI was unrelated to tumor site. When MSI-H tumors were excluded, no tumor site-related differences were found except for age, which remained associated with proximal cancers (P= 0.030). Proximal site was associated with improved disease-free survival in all patients (P= 0.042), but not when MSI-H cases were excluded (P= 0.236). MSI-H status or loss of mismatch repair proteins, diploidy, and lower PI were associated with improved survival rates. CONCLUSIONS: Tumor site-related differences in clinicopathological variables, biomarkers, and prognosis of sporadic colon cancers can be explained by the inclusion of MSI-H cases. Older age, however, is associated with proximal tumor site independent of MSI status.
OBJECTIVE:Colon cancers with high frequency microsatellite instability (MSI-H) are preferentially located in the proximal colon. Given that 15-20% of sporadic colon cancers are MSI-H, we determined whether tumor site-specific differences in clinicopathological variables, biomarkers, and prognosis are due to inclusion of MSI-H cases. METHODS: TNM stage II and III primary colon carcinomas (N = 528) from patients enrolled in 5-fluorouracil-based adjuvant trials were analyzed for MSI using 11 microsatellite markers. Immunostaining for DNA mismatch repair (hMLH1, hMSH2, hMSH6) and p53 proteins was performed. DNA ploidy (diploid vs aneuploid/tetraploid) and proliferative indices (PI: S-phase + G(2)M) were analyzed by flow cytometry. RESULTS:MSI-H was found in 95 (18%) colon cancers. Proximal tumors (N = 286) were associated with MSI-H, older age (>65 yr), poor differentiation, and diploid DNA content compared with distal tumors (all P< or = 0.016). Nuclear p53 staining was more frequent in distal tumors (P= 0.002); PI was unrelated to tumor site. When MSI-H tumors were excluded, no tumor site-related differences were found except for age, which remained associated with proximal cancers (P= 0.030). Proximal site was associated with improved disease-free survival in all patients (P= 0.042), but not when MSI-H cases were excluded (P= 0.236). MSI-H status or loss of mismatch repair proteins, diploidy, and lower PI were associated with improved survival rates. CONCLUSIONS:Tumor site-related differences in clinicopathological variables, biomarkers, and prognosis of sporadic colon cancers can be explained by the inclusion of MSI-H cases. Older age, however, is associated with proximal tumor site independent of MSI status.
Authors: Arantza Fariña Sarasqueta; Eliane C M Zeestraten; Tom van Wezel; Gesina van Lijnschoten; Ronald van Eijk; Jan Willem T Dekker; Peter J K Kuppen; Ines J Goossens-Beumer; Valery E P P Lemmens; Cornelis J H van de Velde; Harm J T Rutten; Hans Morreau; A J C van den Brule Journal: Cell Oncol (Dordr) Date: 2011-08-10 Impact factor: 6.730
Authors: Mine S Cicek; Noralane M Lindor; Steven Gallinger; Bharati Bapat; John L Hopper; Mark A Jenkins; Joanne Young; Daniel Buchanan; Michael D Walsh; Loic Le Marchand; Terrilea Burnett; Polly A Newcomb; William M Grady; Robert W Haile; Graham Casey; Sarah J Plummer; Lisa A Krumroy; John A Baron; Stephen N Thibodeau Journal: J Mol Diagn Date: 2011-05 Impact factor: 5.568
Authors: Frank A Sinicrope; Rafaela L Rego; Kenji Okumura; Nathan R Foster; Michael J O'Connell; Daniel J Sargent; Harold E Windschitl Journal: Clin Cancer Res Date: 2008-09-15 Impact factor: 12.531
Authors: Shuji Ogino; Katsuhiko Nosho; Yoshifumi Baba; Shoko Kure; Kaori Shima; Natsumi Irahara; Saori Toyoda; Li Chen; Gregory J Kirkner; Brian M Wolpin; Andrew T Chan; Edward L Giovannucci; Charles S Fuchs Journal: Am J Gastroenterol Date: 2009-06-09 Impact factor: 10.864