CK7 expression associates with the location, differentiation, lymph node metastasis, and the Dukes' stage of primary colorectal cancers

J Cancer. 2019 Jun 2;10(11):2510-2519. doi: 10.7150/jca.29397. eCollection 2019.

Abstract

Purpose: Most colorectal cancers (CRCs) show positive immunohistochemical (IHC) staining for CK20 and negative staining for CK7. However, in clinical settings, some CRCs show positive IHC staining for CK7, and the clinicopathological significance of this needs to be studied. This study investigated the clinicopathological significance of CK7 positivity in CRCs. Materials and Methods: A total of 178 patients with CRC were used to study the clinicopathological significance of CK7 positivity. Western blotting and immunocytochemical (ICC) staining were used to compare the expression levels of CK7 before and after CoCl2 treatment. Results: CK7 expression was associated with the location, differentiation, lymph node metastasis, and the Dukes' stage of CRCs. CK7 positive cells were mainly distributed at the edge of cancer nests, at the invasion front, as single stromal polyploid giant cancer cells (PGCCs), in tumor buds, in intravascular tumor emboli, and in a micropapillary pattern. Results of ICC staining showed that CK7 expression was almost negative in LoVo and HCT116 before CoCl2 treatment. After CoCl2 treatment, the PGCCs and their daughter cells of LoVo and HCT116 yielded positive results in CK7 ICC staining. Results of western blotting also confirmed that there was higher CK7 expression in LoVo and HCT116 after CoCl2 treatment than in the control. Conclusion: CRC cells expressing CK7 may have strong invasive and metastatic abilities. Some metastasis-related morphological characteristics in CRCs including the invasion front, micropapillary pattern, tumor emboli, and single stromal PGCCs associated with CK7 positive expression.

Keywords: colorectal cancer; cytokeratin 7; micropapillary pattern; polyploidy giant cancer cells; tumor budding.