Original ArticleCytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas
Introduction
A metastatic lesion can be the first clinical presentation of a neoplastic process, probably accounting for more than 10% of all new tumor diagnoses [1]. Although modern imaging technology has resulted in improvements in the identification of primary tumors, in most patients, the origin remains unknown. Therefore, the pathologist has acquired an increasingly important diagnostic role in characterizing the site of origin of these tumors [2].
Immunohistochemistry has been shown to be a useful tool in the identification of the primary site. It is the least invasive diagnostic technique and is certainly less expensive than imaging techniques. The generation and availability of new antibodies that are specific for a wide range of antigens and tissues that work on routinely fixed, paraffin-embedded material will ensure that this technique will continue to offer useful information in the search for elusive primary sites.
Cytokeratins are among a group of approximately 20 cytoskeletal structural proteins present in normal epithelia, and their expression is maintained during malignant transformation [3]. Because CK expression is usually preserved in neoplastic cells, the use of specific antibodies is of value in determining the origin of metastatic carcinomas. In normal tissue, CK7 is expressed in simple epithelia of breast, lung, mesothelium, female genital tract, and urinary bladder, with limited expression in gastric and intestinal mucosa [4], [5]. CK20 is a major cellular protein of mature enterocytes and goblet cells in the intestinal tract, urothelium, and Merkel cells in the skin [6]. The relative expression of CK20 and CK7 has been observed to vary among different epithelial tumors, and these markers are currently used as diagnostic tools to help determine the site of origin of metastatic carcinomas [7], [8], [9], [10], [11]. For example, the CK20+/CK7− immunoprofile has been considered characteristic for colonic adenocarcinoma, and has been used to distinguish it from adenocarcinomas of other origins, such as female genital tract, lung, breast, and liver. Because cytoplasmic CK7 expression in colorectal adenocarcinoma is considered rare, CK7 positivity in metastatic carcinoma is often considered to exclude a colorectal primary [9], [12], [13]. However, not all colorectal carcinomas show the CK20+/CK7− expression pattern; a substantial proportion of colorectal carcinomas are CK20− or CK7+ [14], [15], [16].
In the present study, we investigated the expression profile of CK7 and CK20 in 196 primary colorectal adenocarcinomas in the light of the potential applicability of these markers in the clinical context of metastatic adenocarcinomas.
Section snippets
Case selection and tissue samples
Paraffin-embedded tissue sections were obtained from archival material from 196 patients who underwent resection for primary colorectal carcinoma between January 2005 and December 2009. All cases were selected from patient files at the Department of Pathology, Fatih University Hospital. Pathological findings, including histological type, histological differentiation, depth of invasion, and lymph node status, were obtained from hematoxylin and eosin-stained sections.
All cases were reviewed to
Results
Histologically normal colonic epithelium stained positively for CK20. Cytoplasmic CK20 immunoreactivity was more prominent in the surface epithelium and tended to diminish toward the crypts (Fig. 1A). We also observed CK7 immunoreactivity in normal colonic epithelium, and this immunoreactivity tended to be focal in the surface and the crypt epithelium (Fig. 1B).
CK20 expression was detected in 159 of 196 (81.1%), and CK7 expression was detected in 34 of 196 (17.3%) colorectal carcinomas. CK20
Discussion
Cytokeratins (CKs) are cytoplasmic intermediate filaments found in the epithelial cells, and different cytokeratin proteins are distributed in a tissue-specific fashion [3]. Carcinomas usually have a characteristic cytokeratin profile, similar to that of its native epithelium that can still be maintained in its metastasis [8], [11], [19]. This consistency of cytokeratin expression profile in specific epithelial neoplasms has been used to identify the origin of a metastatic tumor [9], [11], [12]
Acknowledgements
The results of this study were partially presented in the poster session of the 21st European Congress of Pathology, 8–13 September 2007, İstanbul, Turkey.
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