Colorectal polyps and other precursor lesions

Burgart, Lawrence J.

doi:10.1016/s0889-8553(02)00056-0

Cited by 28 publications

(20 citation statements)

References 51 publications

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“…However, only a small proportion of all adenomas progress to become invasive carcinomas (Burgart 2002). Alterations present at the early stages are likely to play a crucial role in CRC progression.…”

Section: Discussionmentioning

confidence: 99%

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p53 Nuclear Accumulation and Bcl-2 Expression in Contiguous Adenomatous Components of Colorectal Adenocarcinomas Predict Aggressive Tumor Behavior

Shanmugam

Katkoori

Jhala

et al. 2007

J Histochem Cytochem.

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For subsets of colorectal adenocarcinoma (CRC) patients, nuclear accumulation of p53 (p53nac) and Bcl-2 expression are prognostic indicators. To understand their role in the progression of CRC we evaluated 90 CRCs and their contiguous adenomatous components (CAdCs) for immunohistochemical expression of these markers. In general, p53nac and Bcl-2 expression was significantly increased when comparing normal colonic epithelia to CAdCs and CRCs. Thirteen (14%) CAdCs that demonstrated p53nac continued to express p53nac in their contiguous CRCs. A similar trend was observed in Bcl-2 expression in that the majority of CAdCs expressing Bcl-2 continued to express it in their matching CRCs (39/44). Patients whose CAdCs and their contiguous CRCs demonstrate p53nac had shorter median survival (35.9 months) than those patients whose CAdCs and CRCs did not (80.56 months). However, patients whose CAdCs had p53nac and lacked Bcl-2 expression had the lowest median survival (15.74 months) when compared with patients whose CAdCs did not demonstrate p53nac but had increased expression of Bcl-2 (71.77 months). These findings suggest that in those adenomas that demonstrate p53nac but lack Bcl-2 expression, their contiguous CRCs are more likely to be aggressive as they progress.

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Section: Discussionmentioning

confidence: 99%

“…Adenomas are much more common than adenocarcinomas and only a few will become malignant (Burgart 2002). The important predictors of risk of developing invasive cancer from adenomas include the type and size of the adenoma and degree of dysplasia (Hamilton and Aaltonen 2000).…”

mentioning

confidence: 99%

p53 Nuclear Accumulation and Bcl-2 Expression in Contiguous Adenomatous Components of Colorectal Adenocarcinomas Predict Aggressive Tumor Behavior

Shanmugam

Katkoori

Jhala

et al. 2007

J Histochem Cytochem.

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“…Besides the traditional adenoma, upon which the Vogelstein model is based, another common lesion is the hyperplastic (metaplastic or serrated) polyp, which has been widely dismissed as innocuous. However, a new understanding of the pathology and natural history of hyperplastic polyps has emerged over the past decade (3,4,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Serrated polyps encompass the common hyperplastic polyps found most frequently in the distal bowel of older patients, and also occurring as satellite nodules around rectal cancers that regress after resection (24).…”

Section: The Serrated Pathway Of Colorectal Cancer Developmentmentioning

confidence: 99%

The Case for a Genetic Predisposition to Serrated Neoplasia in the Colorectum: Hypothesis and Review of the Literature

Young

Jass

2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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In recent years, an alternative pathway of colorectal cancer development has been described in which serrated polyps replace the traditional adenoma as the precursor lesion. Importantly, serrated polyps and a subset of colorectal cancer show largely nonoverlapping mutation profiles to those found in adenomas and the majority of colorectal cancer. These genetic alterations include activating mutation of the BRAF proto-oncogene and widespread gene promoter hypermethylation (CpG island methylator phenotype or CIMP). Up to 15% of colorectal cancer is likely to develop on the basis of a strong genetic predisposition. The two most wellcharacterized syndromes, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer (Lynch syndrome), both develop via the adenoma-carcinoma pathway and together account for approximately one third of familial colorectal cancer. We have recently described 11 families in which there is evidence that the genetic predisposition to autosomal dominant colorectal cancer is linked to the serrated pathway. This condition, serrated pathway syndrome, and the related condition, hyperplastic polyposis, the presentation of which suggests a recessive mode of inheritance, represent two syndromes in which BRAF mutation and methylation co-occur within serrated precursor lesions. Further, CIMP is observed in the normal colonic mucosa of individuals with hyperplastic polyposis consistent with a field defect in epigenetic regulation. The spectrum of serrated neoplasia may also implicate the apparently sporadic and later onset subset of colorectal cancer with high levels of microsatellite instability. The tendency for these lesions to be multiple, associated with smoking, and to show frequent BRAF mutation and CIMP points to a defect that may result from interactions between the environment and a weakly penetrant genetic alteration. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1778 -84)

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“…3 However, not all adenomas necessarily progress to invasive carcinomas, and the risk of malignant transformation depends on, for example, their histopathological subtype. 4 Approximately 80% of all colorectal carcinomas show aneuploidy. 5 Cytogenetic and molecular cytogenetic analyses have revealed that tumor-specific gains and losses of entire chromosomes or chromosome arms are early genome mutations.…”

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confidence: 99%

Genomic instability and oncogene amplifications in colorectal adenomas predict recurrence and synchronous carcinoma

et al. 2011

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Individual colorectal adenomas have different propensities to progress to invasive disease. In this study, we explored whether these differences could be explained by gene copy number alterations. We evaluated 18 adenomas of patients without synchronous or subsequent carcinoma (6.5 years follow-up), 23 adenomas of carcinoma patients, and 6 related carcinomas. All samples were measured for their DNA ploidy status. Centromere probes for chromosomes 17 and 18, as well as gene-specific probes for SMAD7, EGFR, NCOA3, TP53, MYC, and RAB20 were assessed by multicolor fluorescence in situ hybridization. An increased genomic instability index of CEP17, SMAD7, and EGFR, as well as TP53 deletions and MYC amplifications defined adenomas of patients with synchronous carcinoma (Po0.05). Diploid NCOA3 signal counts were associated with longer adenoma recurrence-free surveillance (P ¼ 0.042). In addition, NCOA3, MYC, EGFR, and RAB20 amplifications, as well as TP53 deletions correlated with increased DNA stem line values and/or aneuploidy in adenomas (Po0.05). Furthermore, aberrations of NCOA3, MYC, and RAB20 were associated with histopathologically defined high-risk adenomas (Po0.05). RAB20 amplifications were also correlated with high-grade dysplastic adenomas (P ¼ 0.002). We conclude that genomic instability in colorectal adenomas is reflected by EGFR, MYC, NCOA3, and RAB20 amplifications that do correlate with histomorphological features and are indicative for adenoma recurrence and the presence of synchronous carcinomas.

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Colorectal polyps and other precursor lesions

Cited by 28 publications

References 51 publications

p53 Nuclear Accumulation and Bcl-2 Expression in Contiguous Adenomatous Components of Colorectal Adenocarcinomas Predict Aggressive Tumor Behavior

p53 Nuclear Accumulation and Bcl-2 Expression in Contiguous Adenomatous Components of Colorectal Adenocarcinomas Predict Aggressive Tumor Behavior

The Case for a Genetic Predisposition to Serrated Neoplasia in the Colorectum: Hypothesis and Review of the Literature

Genomic instability and oncogene amplifications in colorectal adenomas predict recurrence and synchronous carcinoma

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