Regarding the discrepancies of endosialin localization,
in stroma and/or in tumour cells found in different stu-
dies, several factors may be responsible, including the
number and clinicopathological characteristics of the
patients included in such studies, as well as the methods
used in the s ame. For example, if tissue arrays were
used for staining endosialin , it is possible that a
limited sample of tissue was obtained from the tumour
blocks and the selected arrays may not be representative
of the complete characteristics of the tumour because of
tumour heterogeneity. In the present study, we used
ordinary sections for staining endosialin and observed
that only 34% of the cases showed positive endosialin
expression in tumour ce lls. In fact, in some positive
cases, only a few po sitive tumour cells were determined
in the entire tumour sections. In addition, s ome studies
which em ployed real-time PCR or quantitative real-ti me
PCR methods could not determine the location of the
expression [20,21]. In the present study, we used immu-
nohistochemical staining, which is one of the best meth-
ods of identifying the location of endosialin expression.
Endosialin expression may be involved in the progres-
sion of rectal cancers. It is also r elated to Cox-2, p73,
and PRL expression. Ho wever, a direct relationship
between endosialin expression and RT responses in
patients was not found.
The authors are grateful to Prof. Clare M. Isacke and Dr. Nicole Simonavicius
for providing the endosialin antibody. The study was supported by grants
from the Service Centre for Experts and Scholars of Hebei Province of China
to ZYZ and the Swedish Cancer Foundation and the Health Research
Council of the South-East of Sweden to XFS.
Department of Oncology, Institute of Clinical and Experimental Medicine,
Linköping University, Linköping, S-581 85, Sweden.
Pathology, Tangshan Gongren Hospital, Tangshan, PR China.
Centre, First Hospital of Hebei Medical University, Shijiazhuang, PR China.
Division of Biomedicine, School of Life Science, University of Skövde,
Department of Oncology, Karolinska University Hospital,
ZYZ conducted the experiments, analyzed the results with XFS, and wrote
the drafts of the manuscript. ZYZ and HZ read the immunohistochemical
slides. AG provided the samples for the experiments and information
regarding the therapy. XFS designed the experiments and helped write the
manuscript. All authors have read and approved the final manuscript.
The authors declare that they have no competing interests.
Received: 29 October 2009 Accepted: 1 March 2011
Published: 1 March 2011
1. Cancer incidence in Sweden. The National Board of Health and Welfare;
2. MacFarlane JK, Ryall RD, Heald RJ: Mesorectal excision for rectal cancer.
Lancet 1993, 341(8843):457-460.
3. Swedish rectal cancer trial: Improved survival with preoperative
radiotherapy in resectable rectal cancer. N Engl J Med 1997,
4. Elenbaas B, Weinberg RA: Heterotypic signaling between epithelial tumor
cells and fibroblasts in carcinoma formation. Exp Cell Res 2001,
5. Bhowmick NA, Neilson EG, Moses HL: Stromal fibroblasts in cancer
initiation and progression. Nature 2004, 432(7015):332-337.
6. Rettig WJ, Garin-Chesa P, Healey JH, Su SL, Jaffe EA, Old LJ: Identification
of endosialin, a cell surface glycoprotein of vascular endothelial cells in
human cancer. Proc Nat Acad Sci USA 1992, 89(22):10832-10836.
7. Christian S, Ahorn H, Koehler A, Eisenhaber F, Rodi HP, Garin-Chesa P,
Park JE, Rettig WJ, Lenter MC: Molecular cloning and characterization of
endosialin, a C-type lectin-like cell surface receptor of tumor
endothelium. J Biol Chem 2001, 276(10):7408-7414.
8. Opavsky R, Haviernik P, Jurkovicova D, Garin MT, Copeland NG, Gilbert DJ,
Jenkins NA, Bies J, Garfield S, Pastorekova S: Molecular characterization of
the mouse Tem1/endosialin gene regulated by cell density in vitro and
expressed in normal tissues in vivo. J Biol Chem 2001,
9. St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E,
Lal A, Riggins GJ, Lengauer C, Vogelstein B, et al: Genes expressed in
human tumor endothelium. Science 2000, 289(5482):1197-1202.
10. MacFadyen J, Savage K, Wienke D, Isacke CM: Endosialin is expressed on
stromal fibroblasts and CNS pericytes in mouse embryos and is
downregulated during development. Gene Exp Patterns 2007, 7(3):363-369.
11. MacFadyen JR, Haworth O, Roberston D, Hardie D, Webster MT, Morris HR,
Panico M, Sutton-Smith M, Dell A, van der Geer P, Wienke D, Buckley CD,
Isacke CM: Endosialin (TEM1, CD248) is a marker of stromal fibroblasts
and is not selectively expressed on tumour endothelium. FEBS Lett 2005,
12. Simonavicius N, Robertson D, Bax DA, Jones C, Huijbers IJ, Isacke CM:
Endosialin (CD248) is a marker of tumor-associated pericytes in high-
grade glioma. Mod Pathol 2008, 21(3):308-315.
13. Christian S, Winkler R, Helfrich I, Boos AM, Besemfelder E, Schadendorf D,
Augustin HG: Endosialin (Tem1) is a marker of tumor-associated
myofibroblasts and tumor vessel-associated mural cells. Am J Pathol
14. Tomkowicz B, Rybinski K, Foley B, Ebel W, Kline B, Routhier E, Sass P,
Nicolaides NC, Grasso L, Zhou Y: Interaction of endosialin/TEM1 with
extracellular matrix proteins mediates cell adhesion and migration. Proc
Natl Acad Sci USA
Nanda A, Karim B, Peng Z, Liu G, Qiu W, Gan C, Vogelstein B, St Croix B,
Kinzler KW, Huso DL: Tumor endothelial marker 1 (Tem1) functions in the
growth and progression of abdominal tumors. Proc Natl Acad Sci USA
16. Pachkoria K, Zhang H, Adell G, Jarlsfelt I, Sun XF: Cox-2 expression in rectal
cancer patients with or without preoperative radiotherapy. Int J Radiat
Oncol Biol Phys 2005, 63(3):739-744.
17. Pfeifer D, Gao J, Adell G, Sun XF: Expression of the p73 protein in rectal
cancers with or without preoperative radiotherapy. Int J Radiat Oncol Biol
Phys 2006, 65(4):1143-1148.
18. Wallin A, Svanvik J, Adell G, Sun XF: Expression of PRL proteins at invasive
margin of rectal cancers in relation to preoperative radiotherapy. Int J
Radiat Oncol Biol Phys 2006, 65(2):452-458.
19. Carson-Walter EB, Watkins DN, Nanda A, Vogelstein B, Kinzler KW, St Croix B:
Cell surface tumor endothelial markers are conserved in mice and
humans. Cancer Res 2001, 61(18):6649-6655.
20. Rmali KA, Puntis MC, Jiang WG: Prognostic values of tumor endothelial
markers in patients with colorectal cancer. World J Gastroenterol 2005,
21. Davies G, Cunnick GH, Mansel RE, Mason MD, Jiang WG: Levels of
expression of endothelial markers specific to tumour-associated
endothelial cells and their correlation with prognosis in patients with
breast cancer. Clin Exp Metastasis 2004, 21(1):31-37.
22. Brady J, Neal J, Sadakar N, Gasque P: Human endosiali n ( tumor
endothelial marker 1) is abundantly expressed in highly malignant
and inv asive brain tu mor s. J Neuropathol Exp Neurol 2004,
Zhang et al. BMC Cancer 2011, 11:89
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