Distinct molecular patterns based on proximal and distal sporadic colorectal cancer: arguments for different mechanisms in the tumorigenesis

Azzoni, Cinzia; Bottarelli, Lorena; Campanini, Nicoletta; Cola, Gabriella Di; Bader, Giovanni; Mazzeo, Antonio; Salvemini, Carlo; Morari, Silvia; Mauro, Davide Di; Donadei, Enrico; Roncoroni, L; Bordi, Cesare; Sarli, Leopoldo

doi:10.1007/s00384-006-0093-x

Cited by 104 publications

(81 citation statements)

References 72 publications

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“…Furthermore, mucinous tumors were found more frequently in the right side only when it was compared to rectum (p=0.014) ( Table V). This finding is also in agreement with some (5,12,16,17) but not all previous reports (19,20). Survival was not affected by tumor location in our hands (Table II) contrary to studies reporting a better survival for proximal colon cancers (8,12) and a worse survival for rectal tumors (21).…”

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confidence: 93%

“…We found that proximal cancers exhibit significantly higher tumor grade as compared to distal colon (p=0.009) and rectal cancers (p=0.003) ( Table V). This is in agreement with two previous reports (12,16), whereas other studies did not show any regional difference in tumor grade (17). Furthermore, mucinous tumors were found more frequently in the right side only when it was compared to rectum (p=0.014) ( Table V).…”

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confidence: 93%

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Characterization of rectal, proximal and distal colon cancers based on clinicopathological, molecular and protein profiles

Minoo¹

2010

Int J Oncol

161

120

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Abstract. Accumulating evidence suggests that colorectal cancer (CRC) should be viewed as a heterogeneous disease, with proximal and distal CRCs showing multiple biological and clinical differences. The aim of this study was to develop a clinicopathological, molecular and protein profile for CRCs based on their region and thus providing insight into their heterogeneity. CRC patients (n=399) were evaluated for clinicopathologic and molecular features including K-RAS, BRAF and MSI status. Tumors were also screened for expression of 50 immunohistochemical markers linked to major signaling pathways involved in tumor-progression or immune response. Proximally located tumors show significantly larger tumor size, higher T-stage, higher tumor grade and more frequent mucinous histologic subtype compared to the distal colon and rectum. The frequency of BRAF mutation and MSI-high phenotype were significantly higher in proximal colon cancers. There is a significant difference in regional expression of 10 tumor-associated markers (CDX2, CD44v6, CD44s, TOPK, nuclear ß-catenin, pERK, APAF-1, E-cadherin, p21 and bcl2) and 4 immune response markers (CD68, CD163, FoxP3 and TIA-1). In multivariate analysis CD44s, CD44v6, nuclear ß-catenin and CD68 expression was found to best discriminate left-versus right-sided colon cancers. Tumor diameter, pT stage and MSI status best distinguish right-sided colon cancers from rectal cancers and pT stage and E-cadherin best discriminate left-sided colon cancers and rectal cancers. These data along with existing evidence for the presence of distinct regional embryological origin and gene expression profile are highly supportive of the concept that proximal and distal CRCs are distinct clinicopathologic entities.

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confidence: 93%

Section: ------------------------------------------------------------supporting

confidence: 93%

Characterization of rectal, proximal and distal colon cancers based on clinicopathological, molecular and protein profiles

Minoo¹

2010

Int J Oncol

161

120

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“…Previous reports have shown differences between the right-side colon (including the caecum, ascending colon, and transverse colon) and the left-side colon (including the descending colon, sigmoid colon, and rectum) in epidemiologic incidence (Gonzalez et al, 2001), morphology (Okamoto et al, 2005), and molecular alterations (Iacopetta, 2002;Azzoni et al, 2007). Meanwhile, other reports revealed these differences between the colon and rectum (Frattini et al, 2004;Kim et al, 2006).…”

Section: Discussionmentioning

confidence: 97%

Genetic and epigenetic alterations of Ras signalling pathway in colorectal neoplasia: analysis based on tumour clinicopathological features

et al. 2007

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Activation of RAS signalling induced by K-ras/BRAF mutations is a hallmark of colorectal tumours. In addition, Ras association domain families 1 and 2 (RASSF1 and RASSF2), the negative regulators of K-ras, are often inactivated by methylation of the promoter region in those tumours. However, reports showing differences in the occurrence of these alterations on the basis of tumour characteristics have been scarce. We analysed K-ras/BRAF mutations and the methylation status of RASSF1 and RASSF2 promoter regions in 120 colorectal adenomas with respect to their clinicopathological features. K-ras/BRAF mutations and RASSF2 methylation were observed in 49 (41%) and 30 (25%) of the samples, respectively, while RASSF1 methylation was observed in only 3 (2.5%). Adenomas with RASSF2 methylation often carried K-ras/BRAF mutations simultaneously (22 out of 30, Po0.01). Multivariate analysis revealed that the concomitance of these alterations was frequently observed in serrated adenomas (odds ratio (OR) 11.11; 95% confidence interval (CI) 1.96 -63.00), but rarely in adenomas located in the sigmoid or descending colon (OR 0.13; 95% CI 0.03 -0.58). A comparison between adenomas and cancers showed a significantly higher prevalence of these alterations in cancers than in adenomas in the proximal colon (58 vs 27%, P ¼ 0.02). Frequency and the time point of the occurrence of Ras signalling disorders differ according to colorectal neoplasia's characteristics, particularly the location.

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“…However, etiological pathways underlying colon cancers proximal to the splenic flexure are different from those distal to the splenic flexure and evidence that risk factors for tumors originating from different colorectal subsites vary is accumulating. 14,15 The aim of this study was to assess the association of prediagnostic plasma concentrations and dietary intakes of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. In addition, analyses for colon cancer were stratified by subsite.…”

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confidence: 99%

Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition

et al. 2014

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Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case–control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (α‐ and β‐carotene, canthaxanthin, β‐cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (α‐, β‐ and γ‐ and δ‐tocopherol) and dietary consumption of β‐carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary β‐carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties.

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Distinct molecular patterns based on proximal and distal sporadic colorectal cancer: arguments for different mechanisms in the tumorigenesis

Abstract: These different features may reflect different genetic pathways of carcinogenesis and support the hypothesis of a different mechanism of cancer development between the proximal and the distal colon, with potential implications in the therapeutic approach.

Cited by 104 publications

References 72 publications

Characterization of rectal, proximal and distal colon cancers based on clinicopathological, molecular and protein profiles

Characterization of rectal, proximal and distal colon cancers based on clinicopathological, molecular and protein profiles

Genetic and epigenetic alterations of Ras signalling pathway in colorectal neoplasia: analysis based on tumour clinicopathological features

Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition

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