Co-expression of cytokeratin and vimentin in colorectal cancer highlights a subset of tumor buds and an atypical cancer-associated stroma

Human Pathology
Sara N MeyerInti Zlobec

Abstract

Tumor buds in colorectal cancer are hypothesized to undergo a (partial) epithelial-mesenchymal transition (EMT). If so, cytokeratin (CK) and vimentin (VIM) co-expression is expected. CK+/VIM+ can also be found in some stromal cells; however, their origin remains unclear. Here, we determine the frequency of CK+/VIM+ tumor cells and characterize the CK+/VIM+ stroma in colorectal cancer. Three cell populations (CK+, VIM+, CK+/VIM+) were sorted using DepArray and fluorescence-activated cell sorting (FACS). Tumor areas were selected to include tumor center, stroma and tumor budding. Fluorescence microscopy was used to visualize co-expressing cells on whole slides. A next-generation tissue microarray (ngTMA) of matched Pan-CK-positive and -negative stroma was constructed and stained for E-cadherin, VIM, Snail1, Twist1, Zeb1 and Zeb2, COL11A1, SPARC, CD90, α-SMA, FAP and WT1. CK+/VIM+ co-expressing tumor cells were detected using all three methods. With DepArray, only tumor budding areas contained CK+/VIM+ cells. The proportion of CK+/VIM+ tumor cells was low (1.5%-22%). CK+ stroma was associated with aggressive tumor features like distant metastasis (P = .0003), lymphatic invasion (P = .0009) and tumor budding (P = .0084). CK+/VIM+ s...Continue Reading

Citations

Sep 10, 2020·Nature Reviews. Clinical Oncology·Alessandro LugliIris D Nagtegaal
May 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cheng-Chan YuSheng-Chun Chiu
Jul 1, 2020·British Journal of Cancer·Inti ZlobecAlessandro Lugli
Jul 31, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Tilman T RauInti Zlobec
Mar 12, 2021·Cell Communication and Signaling : CCS·Susan E LeggettIan Y Wong
Aug 12, 2021·Cancer Control : Journal of the Moffitt Cancer Center·Peng ZhuWei-Jun Wang

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