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

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 CoCl 2 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 CoCl 2 treatment. After CoCl 2 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 CoCl 2 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.

Cytokeratin 7 expression as a predictor of an unfavorable prognosis in colorectal carcinoma

“…Our results differ from those reported in several previous studies over the last two decades regarding anatomic distribution and prognostic significance of CK7 and CK20 expression in CRC. Zhang et al described enrichment of rectal carcinomas in terms of CK7 positivity compared to proximal colon tumors 19 , which sharply contrasts with our finding and of results published by Fei et al 25 of more frequent CK7 expression in right-sided tumors. In line with our results, Bayrak et al found that CK20 + tumors were more frequent in the left colon and rectum, and they found an association between CK20 + status and low-grade tumors.…”

“…Concerning methodology, the best percentage cut-off points for considering CK7 + /CK7 − and CK20 + /CK20 − tumors, remains unresolved. Loupakis et al and Fei et al considered tumors with staining in > 10% of tumor cells to be positive, just as we did with CK7 13 , 25 . Al-Maghrabi considered CRCs staining in > 5% to be positive 5 .…”

“…Moreover, Bayrak et al described a more frequent expression of CK7 in CRCs with regional lymph node metastatic involvement, without association of CK7 with grade 6 . Hernandez et al described a more frequent occurrence of CK7 positivity in advanced stage CRCs than early-stage cancers 10 , Fei et al recently described association of CK7 expression with high-grade and advanced stage including positive lymph nodes 25 ; nevertheless, as with Bayrak 6 , these authors did not perform a survival analysis that included patient follow-up. In our study, CK7 + tumors had worse survival independently from advanced stage in multivariate analysis.…”

“…All this suggests that CK7 positivity represents a particular molecular cytoskeletal phenotype in CRC with more aggressive tumor behavior. Fei et al suggest an explanation via polyploid giant cancer cells (PGCCs) which are basically cancer stem cells associated with tumor budding, vascular invasion, micropapillary pattern, and they are CK7 positive 25 . The authors describe heterogeneity of CK7 expression with accentuation in the budding cells which are more frequently CK7 + .…”

Unusual Faces of Bladder Cancer

“…GATA3 positivity, co-expression of CK7 and CK20, and CDX-2 negativity should resolve the diagnostic dilemma in doubtful cases [ 24 ]. Attention must be paid, however, to the occasional CK7 positivity of some colorectal adenocarcinomas, a finding that is a sign of dismal prognosis [ 26 ].…”