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. 2001 Nov;159(5):1613-7.
doi: 10.1016/s0002-9440(10)63007-6.

The invasion front of human colorectal adenocarcinomas shows co-localization of nuclear beta-catenin, cyclin D1, and p16INK4A and is a region of low proliferation

A Jung  1 , M Schrauder, U Oswald, C Knoll, P Sellberg, R Palmqvist, G Niedobitek, T Brabletz, T Kirchner
Affiliations

The invasion front of human colorectal adenocarcinomas shows co-localization of nuclear beta-catenin, cyclin D1, and p16INK4A and is a region of low proliferation

A Jung et al. Am J Pathol. 2001 Nov.

Abstract

At the invasion front of well-differentiated colorectal adenocarcinomas, the oncogene beta-catenin is found in the nuclear compartment of tumor cells. Under these conditions, beta-catenin can function as a transcription factor and thus activate target genes. One of these target genes, cyclin D1, is known to induce proliferation. However, invasion front of well-differentiated colorectal adenocarcinomas are known to be zones of low proliferation and express the cell cycle inhibitor p16INK4A. Therefore, we investigated the expression profiles of nuclear beta-catenin, cyclin D1, p16INK4A, and the Ki-67 antigen, a marker for proliferation, in serial sections of well-differentiated colorectal adenocarcinomas. Invasion fronts with nuclear beta-catenin were compared with areas from central parts of the tumors without nuclear beta-catenin, for the expression of cyclin D1, p16INK4A, and Ki-67. It was observed that expression of nuclear beta-catenin, cyclin D1, and p16INK4A at the invasion front are significantly correlated. Such areas exhibit low Ki-67 expression indicating a low rate of proliferation. Thus, in colorectal carcinogenesis the function of beta-catenin and its target gene cyclin D1 does not appear to be the induction of tumor cell proliferation. In particular, the function of cyclin D1 should be reconsidered in view of these observations.

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Figures

Figure 1.
Figure 1.
Areas taken from the invasion front (A, C, E) and central parts of the tumor (B, D, F) from the same tumor stained immunohistochemically with antibodies directed against β-catenin (A, B), cyclin D1 (C, D), or Ki-67 (E, F). As serial sections were used comparable tumor regions are shown. G: Statistical analysis of immunohistochemical staining data. Nuclear labeling: rounded percentage value of cells showing nuclear localization (rounding was done in 5% steps); IF, invasion front; TC, central parts of the tumor; p-value (Mann-Whitney test) for correlating location (IF versus TC) with expression of β-catenin, cyclin D1, or Ki-67; p-value, χ test (Fisher’s exact test) for correlating co-localization of antigen pairs: β-catenin/Ki-67, cyclin D1/Ki-67, β-catenin/cyclin D1.
Figure 2.
Figure 2.
Areas taken from the invasion front (A, C, E, G) and central parts of the tumor (B, D, F, H) from the same tumor (tumor 1, A–D; tumor 2, E–H) stained immunohistochemically with antibodies directed against β-catenin (A, B, E, F) and p16INK4A (C, D, G, H). I: Statistical analysis of immunohistochemical staining data. p-value (Mann-Whitney test) for correlating location (IF versus TC) with expression of β-catenin or p16INK4A; p-value, χ test (Fisher’s exact test) for correlating co-localization of β-catenin with p16INK4A. For a more detailed description see Figure 1 ▶ .
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