Original Article
Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas

https://doi.org/10.1016/j.prp.2010.12.005Get rights and content

Abstract

Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are low molecular weight cytokeratins. The expressions of CK7 and CK20 have been studied in various primary and metastatic carcinomas. Their expression patterns may help to distinguish the site of origin of metastatic carcinomas. We investigated the expressions of CK7 and CK20 in 196 cases of colorectal carcinoma. Paraffin sections of 196 colonic adenocarcinomas were randomly selected, retrieved, and immunostained for CK7 and CK20 with a standard avidin–biotin complex method. CK7 was expressed in 34/196 (17.3%) and CK20 in 159/196 (81.1) cases of colorectal adenocarcinoma. CK7−/CK20+ had the greatest proportion (65.8%) in colorectal carcinomas. The CK7+/CK20+ immunophenotype was identified in 30/196 (15.3%), CK7−/CK20− in 33/196 (16.9%), and CK7+/CK20− in 4/196 (2%) colon adenocarcinomas. The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histological grade, location of the tumor, and lymph node metastasis. CK20 positivity was more common in low grade carcinomas than in high grade carcinomas (85.1% versus 47.6%) and in rectal and sigmoid carcinomas than in proximal colon carcinomas (88.2% versus 63.2% and 88.9% versus 63.2%, respectively). Furthermore, CK7 expression was more common in tumors with lymph node metastasis than in non-metastatic tumors (25.3% versus 11%). In conclusion, a considerable number of colorectal carcinomas showed reactivity to CK7 (17.3%) or no reactivity to CK20 (18.9%). Therefore, CK7 positivity or CK20 negativity does not rule out a colorectal origin of metastatic carcinoma.

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.

References (24)

  • N.P. Wang et al.

    Coordinate expression of cytokeratins 7 and 20 defines unique subsets of carcinomas

    Appl. Immunohistochem. Mol. Morphol.

    (1995)
  • C.C. Wauters et al.

    Keratins 7 and 20 as diagnostic markers of carcinomas metastatic to the ovary

    Hum. Pathol.

    (1995)
  • Cited by (93)

    • Cytokeratin 7 and cytokeratin 20 expression in cancer: A tissue microarray study on 15,424 cancers

      2022, Experimental and Molecular Pathology
      Citation Excerpt :

      For example, the reported rate of cytokeratin 7 positivity ranges from 14.3–31% in Merkel cell carcinoma (Bobos et al., 2006; Jensen et al., 2000; Pasternak et al., 2018), 4.2–46.7% in colon cancer (Al-Maghrabi et al., 2018; Fei et al., 2019; Hernandez et al., 2005; Park et al., 2002; Wauters et al., 1995) 38–71.7% in gastric cancer (Chu et al., 2000; Kim et al., 2004; Park et al., 2002) and 84.6–100% in pancreatic carcinoma (Bai et al., 2021; Chu et al., 2000; Matros et al., 2006; Saad et al., 2009). For cytokeratin 20, the literature reports 88–100% positivity in Merkel cell carcinoma (Bobos et al., 2006; Jensen et al., 2000; Pasternak et al., 2018), 62.5%–100% in colon carcinoma (Al-Maghrabi et al., 2018; Bayrak et al., 2011; Hernandez et al., 2005; Rullier et al., 2000), 0–8% in breast cancer (Chu et al., 2000; Malzahn et al., 1998; Tot, 1999b), 30–50% in gastric cancer (Chu et al., 2000; Kim et al., 2004; Park et al., 2002) and 22–100% in bladder cancer (Chu et al., 2000; Genega et al., 2000; Mhawech et al., 2002; Tamboli et al., 2002). These conflicting data are likely to be caused by the use of different staining protocols, antibodies, and interpretation criteria in these studies.

    • B7-H3 and PD-L1 Expression Are Prognostic Biomarkers in a Multi-racial Cohort of Patients with Colorectal Cancer

      2021, Clinical Colorectal Cancer
      Citation Excerpt :

      In our experience, the patient information mimics earlier findings, as the median expression of HHLA2 was 2 (out of a potential score of 1-12); however, there appeared to be no differences in clinical outcomes relative to its expression. The expression patterns of the remaining three proteins (CK7, CK20, and CDX2) were in line with expectation.28,29 Even though we saw an overall low expression prevalence of CK7, one important feature identified is that CK7 is expressed at a higher level in patients presenting with localized disease rather than de novo metastatic disease.

    View all citing articles on Scopus
    View full text