Colorectal carcinomas arising in the hyperplastic polyposis syndrome progress through the chromosomal instability pathway

Abstract

The hyperplastic polyposis syndrome is characterized by the presence within the colon of multiple large hyperplastic polyps. We describe a case of hyperplastic polyposis syndrome associated with two synchronous carcinomas, one of which arises within a pre-existing hyperplastic lesion. Comparative genomic hybridization was used to determine genetic changes in both carcinomas and several associated hyperplastic lesions. Microsatellite analysis at five loci was performed on carcinomas and representative hyperplastic polyps, and p53 status was analyzed by immunohistochemistry. Both carcinomas showed multiple genetic aberrations, including high level gains of 8q and 13q, and loss of 5q. These changes were not seen in the hyperplastic polyps. Microsatellite instability was not seen in the carcinomas, four separate hyperplastic polyps, the hyperplastic polyp with mild adenomatous change associated with the carcinoma, or a separate serrated adenoma. Allelic imbalance in the cancers at D5S346 and D17S938 suggested allelic loss of both p53 and APC, as well as at the loci D13S263, D13S174, D13S159, and D18S49. An early invasive carcinoma in one hyperplastic polyp stained for p53 protein, but the associated hyperplastic polyp was negative. In this case, neoplastic progression followed the typical genetic pathway of common colorectal carcinoma and occurred synchronously with mutation of p53.

Figure 1.

Histological and immunohistochemical appearance of the small carcinoma and its associated hyperplastic lesion. A: A scanning power view shows the polypoid nature of the smaller carcinoma (T2), with a central infiltrative lesion and surrounding hyperplastic epithelium. B: The same lesion is shown at higher magnification, in which the close proximity of carcinoma and hyperplastic-type epithelium can be seen. C: The mildly adenomatous morphology of much of the lesion (HP-T) surrounding the small carcinoma highlights the dense eosinophilic cytoplasm and mild nuclear and architectural atypia seen focally in this lesion. Hematoxylin and eosin. Bars represent 2 mm (A), 400 μm (B), and 50 μm (C). D: p53 immunostaining shows strong positivity for the carcinoma (brown staining), in contrast to the surrounding hyperplastic lesion and normal mucosa. A high-power view of the interface between carcinoma and hyperplastic lesion is shown (bar = 150 μm), and a scanning-power view of the entire lesion is shown in the inset (bar = 2 mm). Hematoxylin counterstain.

Figure 2.

Microscopic features of a typical hyperplastic polyp (A) and the single serrated adenoma (B) seen in the resected colon. For each micrograph, the bar represents 200 μm, and the inset (bottom right of each micrograph) shows a fourfold magnification of the same lesion. Hematoxylin and eosin.

Figure 3.

Representative chromosomes and CGH profiles in the large carcinoma (A) and small carcinoma (B). Chromosomal gains are indicated by green, and losses are shown in red.

Figure 4.

Summary of chromosomal changes observed in the large and small carcinomas. Gains are displayed to the right of the chromosomal ideogram, and losses are shown on the left. Changes in the small carcinoma are shown as solid lines and changes in the large carcinoma as dotted lines. Double lines mark regions affected by high-level gain or loss. Chromosomes that were normal in both lesions are not shown.