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 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.
['Patankar|Madhura|M|', 'Mattila|Taneli|T|', 'Väyrynen|Juha P|JP|', 'Klintrup|Kai|K|', 'Mäkelä|Jyrki|J|', 'Tuomisto|Anne|A|', 'Nieminen|Pentti|P|', 'Mäkinen|Markus J|MJ|', 'Karttunen|Tuomo J|TJ|']
D000230:Adenocarcinoma D000368:Aged D023102:Anoikis D014408:Biomarkers, Tumor D015179:Colorectal Neoplasms D016326:Extracellular Matrix Proteins D005260:Female D005387:Finland D006801:Humans D007150:Immunohistochemistry D008297:Male D008875:Middle Aged D011379:Prognosis D011446:Prospective Studies D016019:Survival Analysis
carcinoma prognosis anoikis extracellular matrix anoikis resistance Colon prognostic markers rectum