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

Jan Hrudka,Karolína Jelínková,Hana Fišerová,Radoslav Matěj,Petr Waldauf

doi:10.1038/s41598-021-97480-4

Jan Hrudka, Karolína Jelínková + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-97480-4

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Abstract

Colorectal carcinoma (CRC) is associated with significant morbidity and mortality worldwide. Cytokeratins (CKs) are widely expressed in various types of carcinomas, whereas in CRC it is usually CK7 − and CK20 + . A subset of CRCs is CK7 + . This study aims to determine the prevalence of CK7 expression in CRC and its impact on overall survival. We analyzed 300 randomly selected surgically treated CRC cases using paraffin embedded tumor tissue samples and evaluated CK7 and CK20 expression using the tissue microarray method. Tumors with positivity > 10% and > 25% of tumor cells were considered CK7 and CK20 positive, respectively. Expression of both CKs and several clinical-pathological variables (stage, grade, laterality, mismatch-repair/MMR status) were evaluated using patient follow up data (Kaplan–Meier analysis of cancer-specific survival (CSS)). Significant results include shorter CSS (restricted mean 4.98 vs. 7.74 years, P = 0.007) and 5-year survival (29.4% vs. 64.6%, P = 0.0221) in CK7 + tumors compared to CK7 − tumors, respectively; without significant association with grade, stage or right-sided location. These results were significant in a multivariate analysis. CK20 + tumors are more frequently MMR-proficient and left-sided. MMR-deficient tumors are more frequently right-sided and had longer survival. CK7 expression, right-sided location (rmean CSS 6.83 vs. 8.0 years, P = 0.043), MMR-proficiency (rmean CSS 7.41 vs. 9.32 years, P = 0.012), and UICC stages III + IV (rmean CSS 6.03 vs. 8.92 years, P < 0.001) of the tumor correlated with negative prognostic outcomes, whereas the most significant results concern stage and CK7 positivity. The result concerning negative prognostic role of CK7 differs from those obtained by several previous studies focused on this topic.

Highlights

Colorectal carcinoma (CRC) is associated with significant morbidity and mortality worldwide
Expression of CK7 is seen in most adenocarcinomas, except for those arising from the colon, prostate, kidney, thymus, carcinoid tumors, and Merkel cell tumors of the skin[4]
Patients with CK7 + in > 10% of tumor cells had a significantly shorter cancer-specific survival (CSS) than CK7 − patients (≤ 10%) CRCs

Summary

Introduction

Colorectal carcinoma (CRC) is associated with significant morbidity and mortality worldwide. Tumors with positivity > 10% and > 25% of tumor cells were considered CK7 and CK20 positive, respectively Expression of both CKs and several clinicalpathological variables (stage, grade, laterality, mismatch-repair/MMR status) were evaluated using patient follow up data (Kaplan–Meier analysis of cancer-specific survival (CSS)). Because of the ambiguous results seen in other studies, we wanted to clarify the prognostic significance of CK7 in CRC The aim of this retrospective study was to (1) assess the relationship between CK7 expression and cancer-specific survival of patients with CRC, and (2) elucidate correlations with well-established prognostic factors, such as tumor stage, tumor grade, histomorphology, CRC anatomical site, and mismatch-repair (MMR) status as widespread routinely used prognostic parameters in colorectal oncology

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