Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel

Risio, Mauro; Coverlizza, S.; Ferrari, A.; Candelaresi, Gianluigi; Rossini, F. P.

doi:10.1016/0016-5085(88)90545-8

Cited by 120 publications

(33 citation statements)

References 29 publications

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“…These results are consistent with reports that in CRC cases (26) and those at increased risk for the disease (27,28), the colorectal crypt proliferation zone (the lower 60%) expands upwardly into the upper 40% of crypts. That E-cadherin expression did not appreciably differ between cases and controls and cases tended to have lower Èh APC expression may suggest that the excess b-catenin expression found in cases could induce a greater proliferative potential than in controls.…”

Section: Discussionsupporting

confidence: 93%

Markers of the APC/β-Catenin Signaling Pathway as Potential Treatable, Preneoplastic Biomarkers of Risk for Colorectal Neoplasms

Ahearn

Shaukat

Flanders

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Malfunctioning of the adenomatous polyposis coli (APC)/b-catenin signaling pathway is both an early and common event in sporadic colorectal cancer. To assess the potential of APC/b-catenin signaling pathway markers as treatable, preneoplastic biomarkers of risk for colorectal neoplasms, we conducted a pilot colonoscopy-based case-control study (51 cases and 154 controls) of incident, sporadic colorectal adenoma.Methods: We evaluated APC, b-catenin, and E-cadherin expression in normal mucosa from the rectum and ascending and sigmoid colon using automated immunohistochemical and quantitative image analysis. Diet, lifestyle, and medical history were assessed with validated questionnaires.Results: In the normal rectal mucosa, the ratio of the proportion of APC expression in the upper 40% of crypts with total b-catenin expression (APC/b-catenin score) was 14.3% greater in controls than in cases [P ¼ 0.02; OR, 0.40; 95% confidence interval (CI), 0.14-1.14]. Compared with controls, in cases, APC expression was 3.2% lower, b-catenin expression was 3.0% higher, and E-cadherin expression was 0.7% lower; however, none of these differences were statistically significant. The APC/b-catenin score statistically significantly differed according to categories of plausible risk factors for colorectal cancer [e.g., it was 17.7% higher among those with 25(OH) vitamin D 3 concentrations ! 27 ng/mL].Conclusions: These preliminary data suggest that the combined expression of APC and b-catenin in the normal rectal mucosa may be associated with risk for incident, sporadic colorectal neoplasms, as well as with modifiable risk factors for colorectal neoplasms.Impact: Our results may help advance the development of treatable, preneoplastic biomarkers of risk for colorectal neoplasms. Cancer Epidemiol Biomarkers Prev; 21(6); 969-79. Ó2012 AACR.

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Section: Discussionsupporting

confidence: 93%

Markers of the APC/β-Catenin Signaling Pathway as Potential Treatable, Preneoplastic Biomarkers of Risk for Colorectal Neoplasms

Ahearn

Shaukat

Flanders

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Tsujitani et al [20] compared the carcinoma component with the adenoma component in carcinomas in adenoma and also found decreased apoptosis in the carcinomas in combination with increased proliferative activity. These findings, in line with earlier observations [23,26], indicate that adenomas arise primarily through increased proliferative activity, which is only partly compensated for by the rate of apoptosis, though it does rise in adenomas. The presumably higher growth rate of carcinomas relative to adenomas may be partly due to a decreased rate of apoptosis.…”

Section: Discussionsupporting

confidence: 92%

Proliferation and apoptosis in proliferative lesions of the colon and rectum

1997

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Classically, neoplasia has been considered to be primarily a disturbance in the regulation of proliferation, but it is now clear that programmed cell death is dysregulated as well as proliferation. The genes that are implicated in the regulation of these processes, such as p53, c-myc and bcl-2, are often also altered in neoplasms. We have studied proliferation and programmed cell death in hyperplastic polyps, adenomas, carcinomas in adenomas and adenocarcinomas of the colorectum, using the MIB-1 antibody which recognizes the Ki-67 proliferation related antigen, and an in situ nick-end labelling procedure for histochemical labelling of proliferating and apoptotic cells. In addition, immunohistochemistry was used to study the expression of the p53, c-myc and bcl-2 proteins. The material studied consisted of 12 samples of normal mucosa, 8 hyperplastic polyps, 39 adenomas with different degrees of dysplasia and including 3 that carried a carcinoma, and 10 adenocarcinomas, all formalin fixed and paraffin embedded. The Ki-67 index indicated that proliferation increased progressively in hyperplasia, through different degrees of dysplasia in adenoma, to reach the highest level (Ki-67 index of 50%) in adenocarcinoma. Apoptosis also increased in hyperplastic polyps and in adenomas, but decreased significantly in adenocarcinomas. p53 Labelling was seen in 77% of the carcinomas but in only 3% of the adenomas. Expression of c-myc increased in adenomas and carcinomas. Furthermore, a shift from predominantly nuclear to predominantly cytoplasmic expression was seen in progressive neoplasms. Expression of bcl-2 was increased in an occasional hyperplastic polyp, but was increased markedly in almost all adenomas. Strikingly, in the adenomas with a carcinoma, the carcinoma showed weaker bcl-2 expression than the adenoma. In 20% of the carcinomas some bcl-2 staining was seen but this was less extensive than in the adenomas. Our findings indicate that in the progression from adenoma to carcinoma both increased proliferation and decreased apoptosis occur. This is paralleled by an increased expression of p53 and an increased and predominantly cytoplasmic expression of cmyc, but a decreased expression of bcl-2. This decreased bcl-2 expression does not lead to an increase in apoptotic activity.

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“…Proliferative index has not been shown to have a prognostic significance in colorectal cancer. 32,33 Furthermore, we and others have previously demonstrated a lack of correlation between p27 and Ki-67 in colorectal adenocarcinoma 16,34 as well as in breast cancer. 13 It is becoming progressively clearer that CKIs have functions other than cell cycle inhibition.…”

Section: Discussionmentioning

confidence: 80%

Down-Regulation of p27 Is Associated with Development of Colorectal Adenocarcinoma Metastases

Thomas

Szigeti

Murphy

et al. 1998

The American Journal of Pathology

138

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The cyclin-dependent kinase inhibitor p27 is a negative regulator of the cell cycle and a potential tumor suppressor gene. Because we had previously demonstrated that loss of p27 protein is associated with aggressive behavior in colorectal adenocarcinomas, we used immunohistochemistry and in situ hybridization to evaluate the potential role of alterations in p27 expression in primary and metastatic colorectal adenocarcinomas. Parallel immunostaining was performed for Ki-67 and p53. We evaluated 13 cases of metachronous and 23 cases of synchronous primary and metastatic colorectal tumor pairs. In the synchronous subgroup (Stage IV tumors) , 57% of the primary tumor and metastases pairs did not express p27 protein and the remainder were low expressors. In the metachronous subgroup , 54% of the primary tumors were low expressors and the remainder high expressors of p27 protein. There was a significant reduction in the expression of p27 in the metachronous metastases (mean positive cells: 14.5%) when compared to the corresponding primary tumors (mean positive cells: 41.8%) , P ‫؍‬ 0.0023. All the primary and metastatic tumors in the metachronous subgroup showed high levels of p27 mRNA expression. There was no association between loss of p27 and either Ki-67 count or p53 expression. Because p27 is known to be up-regulated when epithelial cells are grown in suspension , the down-regulation of p27 in circulating tumor cells may confer the ability to grow in an environment of altered extracellular matrix or intercellular adhesion properties, two situations which may facilitate metastases. (Am J Pathol 1998, 153:681-687)

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Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel

Cited by 120 publications

References 29 publications

Markers of the APC/β-Catenin Signaling Pathway as Potential Treatable, Preneoplastic Biomarkers of Risk for Colorectal Neoplasms

Markers of the APC/β-Catenin Signaling Pathway as Potential Treatable, Preneoplastic Biomarkers of Risk for Colorectal Neoplasms

Proliferation and apoptosis in proliferative lesions of the colon and rectum

Down-Regulation of p27 Is Associated with Development of Colorectal Adenocarcinoma Metastases

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