Colorectal cancer: a tale of two sides or a continuum?: Figure 1

Yamauchi, Mai; Lochhead, Paul; Morikawa, Teppei; Huttenhower, Curtis; Chan, Andrew T.; Giovannucci, Edward; Fuchs, Charles S.; Ogino, Shuji

doi:10.1136/gutjnl-2012-302014

Cited by 222 publications

(216 citation statements)

References 53 publications

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“…Although cancers with MSI had a higher LN yield, this benefit was reduced in the presence of BRAF mutations, a genetic feature associated with a poor outcome. Furthermore, the arbitrarily dichotomized locations of "proximal" and "distal" may be too approximate of an estimate for exploring the subsegmental continuum difference observed in the colon, which affects both the molecular profile and the LN numbers (28). Also, the overall node yield in the current study was high (over 67% had adequate node sampling), as a proxy indicating proper surgery performed for the majority of patients, and all had R0 resections performed ("R0" denotes a surgical resection with free margins proven on histopathology).…”

Section: Discussionmentioning

confidence: 99%

Influence of Microsatellite Instability and KRAS and BRAF Mutations on Lymph Node Harvest in Stage I–III Colon Cancers

Berg

Guriby

Nordgård

et al. 2013

Mol Med

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Lymph node (LN) harvest is influenced by several factors, including tumor genetics. Microsatellite instability (MSI) is associated with improved node harvest, but the association to other genetic factors is largely unknown. Research methods included a prospective series of stage I-III colon cancer patients undergoing ex vivo sentinel-node sampling. The presence of MSI, KRAS mutations in codons 12 and 13, and BRAF V600E mutations was analyzed. Uni-and multivariate regression models for node sampling were adjusted for clinical, pathological and molecular features. Of 204 patients, 67% had an adequate harvest (≥12 nodes). Adequate harvest was highest in patients whose tumors exhibited MSI (79%; odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2-4.9; P = 0.007) or were located in the proximal colon (73%; 2.8, 1.5-5.3; P = 0.002). In multiple linear regression, MSI was a significant predictor of the total LN count (P = 0.02). Total node count was highest for cancers with MSI and no KRAS/BRAF mutations. The independent association between MSI and a high LN count persisted for stage I and II cancers (P = 0.04). Tumor location in the proximal colon was the only significant predictor of an adequate LN harvest (adjusted OR 2.4, 95% CI 1.2-4.9; P = 0.01). An increase in the total number of nodes harvested was not associated with an increase in nodal metastasis. In conclusion, number of nodes harvested is highest for cancers of the proximal colon and with MSI. The nodal harvest associated with MSI is influenced by BRAF and KRAS genotypes, even for cancers of proximal location. Mechanisms behind the molecular diversity and node yield should be further explored.

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Section: Discussionmentioning

confidence: 99%

Influence of Microsatellite Instability and KRAS and BRAF Mutations on Lymph Node Harvest in Stage I–III Colon Cancers

Berg

Guriby

Nordgård

et al. 2013

Mol Med

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“…8 The importance of tumor-host interactions, encompassing pathogens and inflammation, has been highlighted by the recent discovery of a continuum in the frequency of molecular features (including BRAF mutation) in colorectal cancers. 15 As the Japanese authors discuss in their letter, Asian patients with NSCLC have a much higher prevalence of mutation of the epidermal growth factor receptor gene and a lower prevalence of mutation of the K-ras gene (submitted letter IJC-13-0568). RAS and several of its downstream effectors, including BRAF, have been shown to be commonly mutated in broad range of human cancers.…”

Section: Dear Editormentioning

confidence: 99%

“…[16][17][18][19] With the identification of RAS mutation as a strong predictor of clinical resistance to epidermal growth factor receptor (EGFR)-targeted therapies, RAS mutational testing has been incorporated into the routine clinical care of patients with colorectal and lung cancers. 15 It becomes obvious that determining the molecular and viral profiling in lung cancer patients would be a cardinal next step in order to control this lethal disease. Furthermore, the investigation of the interactions between the host and MCPyV should not be limited to the genetic level but should be expanded to the epigenetic mode of gene regulation induced after viral infection.…”

Section: Dear Editormentioning

confidence: 99%

Molecular pathological findings of Merkel cell polyomavirus in lung cancer: A possible etiopathogenetic link?

Αντωνίου

Lasithiotaki

Symvoulakis

et al. 2013

Intl Journal of Cancer

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The proportion of cancers caused by infectious agents, including bacteria, parasitic worms and viruses, was recently estimated to be more than 20%, 1,2 while the contribution of several viruses is particularly high in certain types of cancer. 3Over 50 years of polyomavirus research has provided novel insights into not only the general biological functions in mammalian cells but has also provided a great deal of information as to how conditions can be altered and signaling systems tweaked to produce transformation phenotypes. [4][5][6] Over the past few years, three new members (KIV, WUV and MCPyV) have joined the two previously known (JCV and BKV) human polyomaviruses. [4][5][6] MCPyV was the third novel polyomavirus identified in a rare but aggressive skin cancer of neuroendocrine origin, termed Merkel cell carcinoma. 7 We appreciate the comments of the Japanese research group (submitted letter IJC-13-0568), giving us the opportunity to further discuss the role of polyoma viruses, and particularly that of Merkel virus, in lung carcinogenesis, as a number of studies have recently been published in this interesting research field. [8][9][10][11] Polyoma viruses, such as BK virus (BKV), JC virus (JCV) and MCPyV are typically non-oncogenic. The evidence for their role in human cancer remains controversial, although they have been detected in a variety of human neoplasms. 2The aforementioned viruses BKV, JCV and SV40, or their early proteins can induce tumors in animal models, and can immortalize or transform cultured cells, including human cells. 4,12 However, similar studies on the newly discovered polyoma viruses are lacking.We have read with great interest the commentary by Hashida et al (submitted letter IJC-13-0568), as the authors have shown for the first time in their original study, a prevalence of 17.9% for MCPyV in non-small cell lung cancer (NSCLC) in an Asian population. The current literature in lung cancinogenesis and more specifically in NSCLC has detected a varying prevalence for MCPyV from 5% in Chile, 11 9.1% in Greece 8 to 16.7% in North America. 10 It should also be noted that both HPV and MCPyV are directly associated with 33% of NSCLC cases. Moreover, our preliminary data indicate that in the same set of samples, 8 HPV DNA is detectable in 19% of the specimens (unpublished data).We are of the opinion that these variations in prevalence between studies from different geographical regions emphasize the complexity of regulation levels at different stages in carcinogenesis. Recently, the interplay of the microenvironment, pathogens, immunity, inflammation, cellular epigenetic alterations and various chronic diseases has attracted increasing attention.12-14 Previous studies thus far have shown that factors, such as disease stage, clinical parameters and methodological issues are rather minor issues. It is becoming more evident that further studies are required to determine whether polyomavirus may be placed among the determinants of risk.Smoking is a major risk factor for lung cancer and it is reco...

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“…We included both colon and rectal carcinoma cases, considering the colorectal continuum model. 67 The study pathologist (S.O.) blinded to other data conducted centralized pathology review of all colorectal carcinoma cases, and recorded pathological features including tumor differentiation, and four patterns of histological lymphocytic reaction [Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes (TILs)].…”

Section: Study Populationmentioning

confidence: 99%

Tumor SQSTM1 (p62) expression and T cells in colorectal cancer

et al. 2017

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Evidence suggests that activation of autophagy in neoplastic cells potentiates antitumor immunity through cross-presentation of tumor-associated antigens to T cells and release of immune mediators. The SQSTM1 (sequestosome 1, p62) protein is degraded by activated autophagy, and might enhance immune response to tumor cells. We hypothesized that tumor SQSTM1 expression level might be inversely associated with T-cell densities in colorectal carcinoma tissue. We evaluated tumor SQSTM1 expression by immunohistochemistry in 601 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study. Ordinal logistic regression analyses were conducted to assess the association of tumor SQSTM1 expression with CD3, or FOXP3 C cell density in tumor tissue, controlling for potential confounders, including tumor status of microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation level, and KRAS, BRAF, and PIK3CA mutations. Tumor SQSTM1 expression level was inversely associated with FOXP3 C cell density (p trend D 0.006), but not with CD3C , CD8 C , or CD45RO C cell density (with the adjusted a level of 0.01 for multiple hypothesis testing). For a unit increase in quartile categories of FOXP3 C cell density, multivariable odds ratios were 0.66 [95% confidence interval (CI), 0.45-0.98] for intermediate-level SQSTM1 expression, and 0.55 (95% CI, 0.36-0.83) for high-level SQSTM1 expression, compared with low-level SQSTM1 expression. Tumor SQSTM1 expression is inversely associated with FOXP3 C cell density in colorectal cancer tissue, suggesting a possible role of SQSTM1-expressing carcinoma cells on regulatory T cells in the tumor microenvironment.Abbreviations: ATP, adenosine triphosphate; CI, confidence interval; CIMP, CpG island methylator phenotype; FFPE, formalin-fixed paraffin-embedded; LINE-1, long interspersed nucleotide element-1; MSI, microsatellite instability;

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Colorectal cancer: a tale of two sides or a continuum?: Figure 1

Cited by 222 publications

References 53 publications

Influence of Microsatellite Instability and KRAS and BRAF Mutations on Lymph Node Harvest in Stage I–III Colon Cancers

Influence of Microsatellite Instability and KRAS and BRAF Mutations on Lymph Node Harvest in Stage I–III Colon Cancers

Molecular pathological findings of Merkel cell polyomavirus in lung cancer: A possible etiopathogenetic link?

Tumor SQSTM1 (p62) expression and T cells in colorectal cancer

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