Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer.
BACKGROUND
The aim of this study was to elucidate the prognostic impact of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and aldehyde dehydrogenase-1 (ALDH1) in colorectal cancer.


METHODS
A tissue microarray of 1420 primary colorectal cancers and 57 normal mucosa samples was immunostained for CD133, CD166, CD44s, EpCAM, and ALDH1 in addition to 101 corresponding whole tissue sections. Invasive potential of three colorectal cancer cell lines was tested.


RESULTS
Differences between normal tissue and cancer were observed for all markers (P<0.001). Loss of membranous CD166 and CD44s were linked to higher pT (P=0.002, P=0.014), pN (P=0.004, P=0.002), an infiltrating growth pattern (P<0.001, P=0.002), and worse survival (P=0.015, P=0.019) in univariate analysis only. Loss of membranous EpCAM expression was also linked to higher pN (P=0.023) and infiltrating growth pattern (P=0.005). The CD44s, CD166, and EpCAM expression were lost towards the invasive front. The CD44-/CD166- cells from three colorectal cancer cell lines exhibited significantly higher invasive potential in vitro than their positive counterparts.


CONCLUSIONS
Loss, rather than overexpression, of membranous CD44s, CD166, and EpCAM is linked to tumour progression. This supports the notion that the membranous evaluation of these proteins assessed by immunohistochemistry may be representative of their cell adhesion rather than their intra-cellular functions.
Lugli
A
A
Institute of Pathology, University of Basel, Basel, Switzerland. alugli@uhbs.ch
Iezzi
G
G
Hostettler
I
I
Muraro
M G
MG
Mele
V
V
Tornillo
L
L
Carafa
V
V
Spagnoli
G
G
Terracciano
L
L
Zlobec
I
I
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005326:Fetal Proteins / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics*; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics*; D011379:Prognosis; D012016:Reference Values; D050697:Retinal Dehydrogenase; D013234:Stem Cells / Q000473:pathology; D015996:Survival Rate; D020410:Activated-Leukocyte Cell Adhesion Molecule
D000071916:AC133 Antigen; D000444:Aldehyde Dehydrogenase; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D000071858:Epithelial Cell Adhesion Molecule; D005326:Fetal Proteins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D010455:Peptides; D050697:Retinal Dehydrogenase; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C499379:EPCAM protein, human; C000606023:PROM1 protein, human; C510223:ALDH1A1 protein, human