RESEARCH ARTICLEOpen Access
Endosialin expression in relation to
clinicopathological and biological variables in
rectal cancers with a Swedish clinical trial of
Zhi-Yong Zhang1,2,3, Hong Zhang4, Gunnar Adell5, Xiao-Feng Sun1*
Background: The importance of changes in tumour-associated stroma for tumour initiation and progression has
been established. Endosialin is expressed in fibroblasts and pericytes of blood vessels in several types of tumours,
and is involved in the progression of colorectal cancer. In order to see whether endosialin was related to
radiotherapy (RT) response, and clinicopathological and biological variables, we investigated endosialin expression
in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative RT.
Methods: Endosialin was immunohistochemically examined in normal mucosa, including distant (n = 72) and
adjacent (n = 112) normal mucosa, and primary tumours (n = 135). Seventy-three of 135 patients received surgery
alone and 62 received additional preoperative RT.
Results: Endosialin expression in the stroma increased from normal mucosa to tumour (p < 0.0001) both in RT and
non-RT group. In the RT group, endosialin expression in the stroma was positively associated with expression of
cyclooxygenase-2 (Cox-2) (p = 0.03), p73 (p = 0.01) and phosphates of regenerating liver (PRL) (p = 0.002).
Endosialin expression in the tumour cells of both in the RT group (p = 0.01) and the non-RT group (p = 0.06) was
observed more often in tumours with an infiltrative growth pattern than in tumours with an expansive growth
pattern. In the RT group, endosialin expression in tumour cells was positively related to PRL expression (p = 0.02),
whereas in the non-RT group, endosialin expression in tumour cells was positively related to p73 expression (p =
Conclusions: Endosialin expression may be involved in the progression of rectal cancers, and was related to Cox-2,
p73 and PRL expression. However, a direct relationship between endosialin expression and RT responses in patients
was not found.
Colorectal cancer is one of the most common malignant
diseases in western countries. Rectal cancer is a frequent
presentation, with an estimated 35% of cases found situ-
ated in the rectum . New surgical techniques  and
preoperative radiotherapy (RT)  have improved the
local control and disease-free survival of patients with
rectal cancer. However the incidence of recurrence and
mortality are still high, even following RT. Therefore, it
is important to gain a better understanding of the
changes induced in tumours following RT of rectal
cancer patients and search for new biological markers in
order to evaluate their therapeutic effects.
The initiation and progression of tumours are influ-
enced by the behaviour of the tumour microenviron-
ment, consisting of the extracellular matrix (ECM), the
newly formed vasculature, inflammatory cells and fibro-
blasts [4,5]. Tumour-associated fibroblasts (activated
fibroblasts and myofibroblasts) have a well-recognized
role as a source of paracrine (cell-to-cell) growth factors
* Correspondence: email@example.com
1Department of Oncology, Institute of Clinical and Experimental Medicine,
Linköping University, Linköping, S-581 85, Sweden
Full list of author information is available at the end of the article
Zhang et al. BMC Cancer 2011, 11:89
© 2011 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
that influence the growth, migration and invasion of
cancer cells during the carcinogenic process. Activated
fibroblasts are also responsible for the synthesis, deposi-
tion and remodelling of the ECM in tumour-associated
stroma . Angiogenesis is a multistep process in
tumour progression that involves both endothelial cells
and pericytes. Alternative potential targets for inhibiting
tumours may be involved in the tumour-associated
stroma that contains newly formed blood vessels, active
fibroblasts and ECM proteins.
One of these ECM proteins is endosialin. The gene for
this protein is located in chromosome 11q13 , and its
product is a type I transmembrane protein, which is a
highly sialylated cell surface receptor found conserved in
humans and in mice. Its extracellular portion consists of
five globular domains, which are N-terminal C-type lec-
tin domain, a sushi-like domain, and three epidermal
growth factor (EGF)-like repeats, followed by a mucin-
like region [7,8]. Endosialin was first reported to be
selectively expressed in tumour-associated endothelium,
which results in an alternate designation of tumour
endothelial marker 1 (TEM1) . Recently, this designa-
tion was challenged by a series of studies in which
endosialin was shown to be expressed in pericytes (peri-
endothelial mural cells) and activated fibroblasts [10-14].
Thus, endosialin plays an important role in overall
tumour vasculature . Targeting on endosialin or its
related pathways may therefore offer an attractive thera-
peutic opportunity for cancer patients .
In the present study, we examined endosialin expres-
sion in distant and adjacent normal mucosa, as well as
in primary tumours, from rectal cancer patients, with or
without preoperative RT. We aimed to investigate the
relationships of endosialin expression with RT
responses, and clinicopathological and biological vari-
ables associated with rectal cancers.
Endosialin was immunohistochemically examined in dis-
tant mucosa samples (n = 72, in which 65 cases were
matched with primary tumours), adjacent normal
mucosa samples (n = 112) and primary tumours (n =
135) from the patients with rectal adenocarcinoma. The
patients were from the Southeast Swedish Health Care
region and participated in a Swedish clinical trial of pre-
operative RT between 1987 and 1990 . The distant
normal mucosal samples were taken from a resected
distant margin that was histologically free from tumours,
and adjacent normal mucosa was adjacent to the pri-
mary tumour on the same histologic section. The study
was approved by the ethical committee of the Faculty of
Health Sciences, Universities of Linköping and Uppsala,
Sweden. All participants gave informed consents.
Among 135 patients, 73 patients received surgery alone
and 62 received additional preoperative RT. A total of
25 Gy of radiation was administered in five fractions
before surgery, over a median of 8 days (range, 6-
15 days). Surgery was performed at a median of 3 days
(range, 0-8 days) after RT. None of the patients received
adjuvant chemotherapy before or after surgery. The
mean age of the patients was 67 years (range, 36-
85 years; median, 69 years). All patients were included in
the follow-up, with mean and median follow-up periods
of 86 and 75 months (range, 0-193 months), respectively.
Follow-up sessions were scheduled at the end of 2004, by
which time 49 patients had died from rectal cancer.
The growth pattern of the tumours was classified (by
two pathologists) as either expansive or infiltrative pat-
tern, based on their patterns of growth and invasiveness.
Tumours were graded as well, moderately or poorly dif-
ferentiated. Other patient and tumour characteristics are
presented in Table 1. No statistically significant
Table 1 Characteristics of patients and rectal cancers
n. (%)n. (%)
Numbers of other
To anal verge (cm)
* Other colorectal cancer and/or other type of tumour besides the present
#For T-test, and the other p values for X2test.
Zhang et al. BMC Cancer 2011, 11:89
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The pre-publication history for this paper can be accessed here:
Cite this article as: Zhang et al.: Endosialin expression in relation to
clinicopathological and biological variables in rectal cancers with a
Swedish clinical trial of preoperative radiotherapy. BMC Cancer 2011
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