Putative anoikis‐resistant subpopulations in colorectal carcinoma: a marker of adverse prognosis

Anoikis is a form of apoptosis induced when a cell loses contact with the extracellular matrix (ECM). Anoikis resistance is essential for metastasis formation, yet only detectable by in vitro experiments. We present a method for quantitation of putative anoikis‐resistant (AR) subpopulations in color...

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Published in:APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2020-05, Vol.128 (5), p.390-400
Main Authors: Patankar, Madhura, Mattila, Taneli, Väyrynen, Juha P., Klintrup, Kai, Mäkelä, Jyrki, Tuomisto, Anne, Nieminen, Pentti, Mäkinen, Markus J., Karttunen, Tuomo J.
Format: Article
Language:English
Subjects:
Anoikis
anoikis resistance
Apoptosis
Cancer
carcinoma
Collagen (type IV)
Colon
Colorectal carcinoma
Density
Extracellular matrix
Immunohistochemistry
Laminin
Medical prognosis
Metastases
Metastasis
Prognosis
prognostic markers
Quantitation
rectum
Subpopulations
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Summary:Anoikis is a form of apoptosis induced when a cell loses contact with the extracellular matrix (ECM). Anoikis resistance is essential for metastasis formation, yet only detectable by in vitro experiments. We present a method for quantitation of putative anoikis‐resistant (AR) subpopulations in colorectal carcinoma (CRC) and evaluate their prognostic significance. We studied 137 CRC cases and identified cell subpopulations with and without stromal or extracellular matrix (ECM) contact with hematoxylin‐and‐eosin‐stained sections and immunohistochemistry for laminin and type IV collagen. Suprabasal cells of micropapillary structures and inner cells of cribriform and solid structures lacked both stromal contact and contact with ECM proteins. Apoptosis rate (M30) was lower in these subpopulations than in the other carcinoma cells, consistent with putative AR subpopulation. We determined the areal density of these subpopulations (number/mm2 tumor tissue), and their high areal density independently indicates low cancer‐specific survival. In conclusion, we show evidence that subpopulations of carcinoma cells in micropapillary, cribriform, and solid structures are resistant to anoikis as shown by lack of ECM contact and low apoptosis rate. Abundance of these subpopulations is a new independent indicator of poor prognosis in CRC, consistent with the importance of anoikis resistance in the formation of metastasis.
ISSN:0903-4641
1600-0463
DOI:10.1111/apm.13041