Clinical Investigation
Correlation of Epidermal Growth Factor Receptor With Morphological Features of Colorectal Advanced Adenomas: A Pilot Correlative Case Series

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Abstract

Introduction

The epidermal growth factor receptor (EGFR) pathway is important to colorectal carcinogenesis. Although EGFR is described to be overexpressed in adenomas, to the authors’ knowledge, its relationship with advanced features in adenomas and as a marker for adenoma progression has not been studied.

Methods

Initially, 13 polyps (sizes 3 mm–5.5 cm) from a 63-year-old patient were stained for EGFR. Subsequently, a validation group of 95 adenomas from 16 patients were graded semiquantitatively for EGFR staining. Size and villous features of the adenomas were evaluated by 2 independent pathologists and compared with EGFR expression. To be classified as advanced, adenomas needed to be greater than 1 cm and fulfill 1 of the 2 criteria—villous component >20% to 25% or presence of high-grade dysplasia.

Results

In the index case, the large 5.5 cm tubulovillous adenoma had EGFR positivity in all of its neoplastic cells, whereas another 2 cm tubular adenoma with focal villous features had 30% EGFR positivity. All other polyps and normal colonic mucosa were negative for EGFR. In 95 adenomas from 16 additional patients, there was a significant correlation of EGFR positivity with adenoma size ≥1 cm and villous features (all P < 0.001). The odds of EGFR expression in advanced adenomas were 17.3 times higher than nonadvanced adenomas (P < 0.001).

Conclusions

These findings suggest that EGFR overexpression is associated with advanced colorectal adenomas. Further larger studies are needed to explore EGFR expression as a biomarker for adenoma progression.

Section snippets

Genesis of This Report—Initial Case

A 63-year-old man presented with iron-deficiency anemia without any family history of colon cancer. On colonoscopy, 8 polypoid lesions were identified and removed. The 2 largest polyps were a single 5.5-cm thick-stalked polyp at the hepatic flexure and a 2-cm pedunculated polyp at the splenic flexure. The 6 other polyps varied from 0.3 to 1 cm in size. A colonoscopy 3 months later showed 5 other small polyps (3–5 mm) in different parts of the colon. All polyps were studied for immunohistochemical

Patient Characteristics

The following results are based on the analysis of the colon adenomas from 16 additional patients. The polyps from the initial patient have not been included in the final analysis. The analyzed population included 16 patients with age ranging from 50 to 82 years. All patients were men, and 13 were whites. The indications for colonoscopy were screening in 8, surveillance in 6, weight loss and hematochezia in 1 each. None of the patients had a family or personal history of colon cancer. A total

DISCUSSION

Encouraged by the findings in our index case and the putative role of EGFR in CRC pathogenesis, in the current pilot case series, we compared the expression of EGFR with some of the morphological features that characterize advanced adenomas. EGFR belongs to a family of plasma membrane receptor tyrosine kinases and controls many important cellular functions from proliferation and angiogenesis to cell death.6., 7. EGFR has been implicated in the pathogenesis of colon cancer8 and is associated

ACKNOWLEDGMENTS

The authors acknowledge the photographic assistance of Dennis Friesen, the technical assistance of the Kansas City VA Pathology and Histology Laboratory and the secretarial assistance of Peggy Knaus.

REFERENCES (20)

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Presented in abstract form at the annual meeting of the College of American Pathologists, Chicago, IL, October 2007 (Arch Pathol Lab Med 2007;131:1432).

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