Relationship between somatostatin receptor subtype expression and clinicopathology, Ki-67, Bcl-2 and p53 in colorectal cancer.

Abstract

To study the SSTR1, 2, 3, 4, 5 expression and their relationships with clinico-pathological factors, cell proliferation, Bcl-2 and p53 expression in colorectal cancer cells.
Immunohistochemical staining of five SSTR subtypes, Ki-67, Bcl-2 and p53 was performed by the standard streptavidin-peroxidase (SP) technique for the paraffin sections of 127 colorectal cancers. and expression of five SSTR subtypes in 40 specimens of normal colorectal mucosae was detected with the same method.
Positive staining for five SSTR subtypes was observed in colorectal cancer cells and normal colorectal mucosae. SSTR1 was the most predominant subtype in both colorectal cancer and normal colorectal mucosa, and the second was SSTR5 or SSTR2. As compared with normal colorectal mucosa, SSTR4 was more frequently expressed in colorectal cancer cells (2.5% vs 18.9%, P<0.05); the expression of SSTR2, 4, 5 in moderately to well differentiated colorectal adenocarcinoma was significantly higher than that in poorly differentiated ones (P<0.05), the SSTR1 expression in colorectal cancer with positive lymph node metastasis was significantly higher than that with negative lymph node metastasis (72.2% and 54.5%,P<0.05). In addition, in the ulcerative type of colorectal cancer, SSTR2 expression was obviously decreased (P<0.05); the correlation did not reach a statistical significance between the five SSTR subtypes expression and Dukes'stages (P>0.05), but the frequency of SSTR1 expression increased with Dukes'stage, while SSTR3 and SSTR5 expression decreased with Dukes' stage. Moreover, there was no correlation between expression of the five SSTR subtypes and other clinicopathological factors such as age, sex, tumor site, tumor depth, distant metastasis. The proliferative indexes in colorectal cancer cells with negative expression of SSTR2 and SSTR3 were significantly higher than that with positive expression (P<0.05). The Bcl-2 expression in colorectal cancer cells with positive expression of SSTR1, 2, 3, 5 was significantly lower than that with negative expression (P<0.05). There was no correlation between five SSTR subtypes and p53 expression.
The most predominant SSTR subtype is SSTR1, and the second is SSTR2 or SSTR5. Five SSTR subtypes play different roles in the development of colorectal cancer. SSTR2 and SSTR3 can inhibit the proliferation and promote apoptosis of tumor cells.

Full text

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COLORECTAL CANCER
Relationship between somatostatin receptor subtype
expression and clinicopathology, Ki-67, Bcl-2 and p53 in
colorectal cancer
Cheng-Zhi Qiu, Chuan Wang, Zhong-Xin Huang, Shi-Ze Zhu, You-Yi Wu, Jian-Long Qiu
Cheng-Zhi Qiu, Shi-Ze Zhu, You-Yi Wu, Department of General
Surgery, Second Affi liated Hospital of Fujian Medical University,
Quanzhou 362000, Fujian Province, China
Chuan Wang, Department of Oncology, Affi liated Union Hospi-
tal to Fujian Medical University, Fuzhou 350001, Fujian Province,
China
Zhong-Xin Huang, Jian-Long Qiu, Department of Pathology,
Second Affi liated Hospital of Fujian Medical University, Quan-
zhou 362000, Fujian Province, China
Supported by Youth Scientific Research Foundation of Health
Department of Fujian Province. No.2003-1-11
Correspondence to: Cheng-Zhi Qiu, Department of General
Surgery, Second Affi liated Hospital of Fujian Medical University,
Quanzhou 362000, Fujian Province, China. qchengzhi@sohu.com
Telephone: +86-595-22768093 Fax: +86-595-22793591
Received: 2005-09-23 Accepted: 2005-11-18

Abstract
AIM: To study the SSTR1, 2, 3, 4, 5 expression and
their relationships with clinico-pathological factors, cell
proliferation, Bcl-2 and p53 expression in colorectal can-
cer cells.
METHODS: Immunohistochemical staining of fi ve SSTR
subtypes, Ki-67, Bcl-2 and p53 was performed by the
standard streptavidin-peroxidase (SP) technique for the
paraffi n sections of 127 colorectal cancers. and expres-
sion of fi ve SSTR subtypes in 40 specimens of normal
colorectal mucosae was detected with the same method.
RESULTS: Positive staining for fi ve SSTR subtypes was
observed in colorectal cancer cells and normal colorectal
mucosae. SSTR1 was the most predominant subtype in
both colorectal cancer and normal colorectal mucosa,
and the second was SSTR5 or SSTR2. As compared with
normal colorectal mucosa, SSTR4 was more frequently
expressed in colorectal cancer cells (2.5 % vs 18.9 %,
P < 0.05); the expression of SSTR2, 4, 5 in moderately
to well differentiated colorectal adenocarcinoma was sig-
nifi cantly higher than that in poorly differentiated ones
(P < 0.05), the SSTR1 expression in colorectal cancer
with positive lymph node metastasis was significantly
higher than that with negative lymph node metastasis
(72.2 % and 54.5 %，P < 0.05). In addition, in the ulcer-
ative type of colorectal cancer, SSTR2 expression was
obviously decreased (P < 0.05); the correlation did not
reach a statistical significance between the five SSTR
subtypes expression and Dukes’stages (P > 0.05), but
the frequency of SSTR1 expression increased with Dukes’
stage, while SSTR3 and SSTR5 expression decreased
with Dukes’ stage. Moreover, there was no correlation
between expression of the fi ve SSTR subtypes and other
clinicopathological factors such as age, sex, tumor site,
tumor depth, distant metastasis. The proliferative in-
dexes in colorectal cancer cells with negative expression
of SSTR2 and SSTR3 were signifi cantly higher than that
with positive expression (P < 0.05). The Bcl-2 expres-
sion in colorectal cancer cells with positive expression
of SSTR1, 2, 3, 5 was signifi cantly lower than that with
negative expression (P < 0.05). There was no correlation
between fi ve SSTR subtypes and p53 expression.
CONCLUSION: The most predominant SSTR subtype
is SSTR1, and the second is SSTR2 or SSTR5. Five SSTR
subtypes play different roles in the development of
colorectal cancer. SSTR2 and SSTR3 can inhibit the pro-
liferation and promote apoptosis of tumor cells.
© 2006 The WJG Press. All rights reserved.
Key words: Somatostatin receptor subtype; Cell prolif-
eration; Apoptosis; p53; Colorectal cancer; Immunohis-
tochemistry
Qiu CZ, Wang C, Huang ZX, Zhu SZ, Wu YY, Qiu JL. Rela-
tionship between somatostatin receptor subtype expression
and clinicopathology, Ki-67, Bcl-2 and p53 in colorectal can-
cer. World J Gastroenterol 2006; 12(13): 2011-2015
http://www.wjgnet.com/1007-9327/12/2011.asp
INTRODUCTION
Somatostatin analogue (SSTA) may inhibit the growth
of various tumor cells by direct interaction with specifi c
somatostatin receptors (SSTR) on tumor cells. However,
confl icting clinical results were obtained in patients with
colorectal cancers treated with SSTA[1]. Many authors
think the rationale for the clinical effi cacy of SSTA in the
management of colorectal cancer may be related to the
direct inhibitory effect of SSTA, consequently, with the
expression of SSTR subtypes on tumor cells[2,3]. To date,
fi ve SSTR subtypes, SSTR1 - SSTR5, have been cloned in
human tissues, however, few researches on their expres-
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Page 2

cance were reported, and the results were inconsistent[3-6].
In this study, we used an immunohistochemical method
to detect the expression of fi ve SSTR subtypes protein in
colorectal cancer cells and to explore correlation between
each subtype expression and clinicopathological factors,
cell proliferation or apoptosis. It will provide the basis for
the treatment of colorectal cancer with SSTA.
MATERIALS AND METHODS
Patients and samples
A total of 127 cases of colorectal adenocarcinoma were
involved in this study. The patients with colorectal carcino-
mas, who underwent surgical resection at the Second
Hospital Affi liated to Fujian Medical University (Quanzhou,
China) from January 1, 2003 to June 30, 2004, had received
neither chemotherapy nor radiation therapy before surgery.
There were 73 men and 54 women, and their mean age
was 58.5 (SD, 13.9; range, 24 - 84) years. specimens were
obtained from right colon (31), left colon (27), rectum
(69). According to the Chinese Dukes’ Staging criteria,
15 cases were stage A, 31 cases were stage B, 46 cases were
stage C and 14 cases were stage D. Among 127 patients,
102 were moderately to well differentiated and 25 poorly
differentiated adenocarcinomas. Meantime, 40 specimens
of morphologically normal colorectal mucosae were ex-
amined from the same patients at a minimal distance of 10
cm from the diseased area.
All specimens were routinely fi xed in neutral-buffered
formalin and embedded in paraffi n. Serial 4 μm sections
were cut from archived paraffi n blocks and subjected to im-
munohistochemical study. In each case, standard hema-
toxylin-eosin staining was employed for routine histological
examination.
Reagents
Goat anti-human SSTR2, SSTR3, SSTR4 and SSTR5 polyc-
lonal antibody were purchased from Santa Cruz Biotech-
nology Co. (California, U.S.A.). Rabbit anti-human SSTR1
polyclonal antibody, mouse anti-human Ki-67 monoclonal
antibody (MBI.1), mouse anti-human Bcl-2 monoclonal
antibody (100/D5), mouse anti-human p53 monoclonal
antibody (DO-7), SP staining kit and DAB kit were
supplied by Maixin-Bio Co., Fuzhou, China.
Methods
The immunohistochemical staining for five SSTR sub-
types, Ki-67, Bcl-2 and p53 expression in colorectal cancer
cells and fi ve SSTR subtypes expression in normal colorec-
tal mucosae were carried out by the standard streptavidin
-peroxidase (SP) technique. Briefl y, after deparaffi nization
and rehydration, the antigen retrieval of the sections was
achieved by incubation in 0.01mol/L citric acid buffer
(pH 6.0) and boiled for 1 min in a pressure cooker, and
then cooled and washed in tap water. The sections were
incubated with hydrogen peroxide for 10 min and washed
in PBS. Nonspecifi c reactions were blocked by incubating
the sections in a solution containing normal serum. The
sections were incubated with a primary antibody (anti-
SSTR1, SSTR2, SSTR3, SSTR4, SSTR5, Ki-67, Bcl-2 or
p53 antibodies) overnight at 4 ℃. The working dilution of
anti-SSTR2, SSTR3, SSTR4, SSTR5 antibodies was 1:400.
Rinsed with PBS, then the sections were incubated for 10
min at room temperature with biotinylated secondary an-
tibody. After washing, streptavidin biotin complex conju-
gated to horse-radish peroxidase was applied for 10 min at
room temperature. Again after three rinses with PBS, the
sections were incubated with diaminobenzidine substrate,
then rinsed with distilled water and counterstained with
hematoxylin, finally dehydrated and cover slipped. The
sections were prepared for microscopic observation. The
known positive colorectal cancer tissues were used as posi-
tive control. As negative control, PBS was used to replace
primary antibody.
Scoring criteria for SSTR subtypes expression
Intensity and percentage of positive cells were used to
evaluate each tissue section. The mean percentage of
positive tumor cells to normal epithelial cells in at least fi ve
areas at 400 magnifi cation was determined and assigned to
one of fi ve categories: 1) 0, < 5 %; 2) 1, 5 % to 24 %; 3) 2,
25 % to 49 %; 4) 3, 50 % to 74 %; and 5) 4, ≥ 75 %. The
intensity of SSTR subtype immunostaining was scored as
0 (achromatic), 1(light yellow), 2(yellow), and 3(brown).
The percentage of positive cells and staining intensity were
multiplied to produce a weighted score for each case. Cases
with weighted scores less than 1 were defi ned as negative;
all others were defi ned as positive.
Evaluation of staining for p53 and Bcl-2
For p53 or Bcl-2 expression, cases with ≤ 10 % positively-
stained tumor cells were defi ned as negative; otherwise, the
defi nition was positive.
Determination of the Ki-67 proliferative index
At least 5 high-power fi elds were chosen randomly in each
section, and 500 cells were counted for each field. The
Ki-67 proliferative index was defi ned as the number of Ki-
67-positive nuclei divided by the total number of colorectal
cancer cells counted and was expressed as a percentage.
Statistical analysis
The statistical software package SPSS 11.5 was used. Clini-
copathological variables associated with SSTR subtypes ex-
pression as well as the correlation between SSTR subtypes
and p53 or Bcl-2 expression were analyzed by either the χ2
test or Fisher’s exact test. The correlation between SSTR
subtypes and proliferative index was analyzed by t test.
P < 0.05 was considered signifi cant.
RESULTS
Expression of fi ve SSTR subtypes
Positive-staining for all SSTR subtypes was identified in
the cytoplasm and membrane of colorectal cancer cells
and normal colorectal mucosa with brown-yellow gran-
ules (Figures 1-5). The positive rates of SSTR1, SSTR2,
SSTR3, SSTR4 and SSTR5 expression were respectively
64.6 % (52/127), 36.2 % (46/127), 18.9 % (24/127), 18.9 %
(24/127), 38.6 % (49/127) in colorectal cancer and 52.5 %
(21/40), 40 % (16/40), 30 % (12/40), 2.5 % (1/40), 32.5 %
(13/40) in normal colorectal mucosa (Table 1). SSTR1 was
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Page 3

the most predominant subtype in both colorectal cancer
and normal colorectal mucosa, and the second was SSTR5
or SSTR2. As compared with normal colorectal mucosa,
SSTR4 was more frequently expressed in colorectal can-
cer cells (2.5 % vs 18.9 %, P < 0.05), and the positive rates
of other subtypes expression were not different between
colorectal cancer and normal colorectal mucosa (P > 0.05).
Correlation between SSTR expression and clinicopathol-
ogical factors
The expression of SSTR2, 4, 5 in moderately to well dif-
ferentiated colorectal adenocarcinoma was significantly
higher than that in poorly differentiated colorectal adeno-
carcinoma (P < 0.05)(Table 2). The SSTR1 expression in
colorectal cancer with positive lymph node metastasis was
significantly higher than that with negative lymph node
metastasis(72.2 % and 54.5 %,P < 0.05).The correlation
did not reach a statistical significance between the five
SSTR subtypes expression and Dukes’ stages(P > 0.05),
but the frequency of SSTR1 expression increased with
Dukes’ stage, while SSTR3 and SSTR5 decreased with
Dukes’ stage. In addition, in the ulcerative type of colorec-
tal cancer, SSTR2 expression was obviously decreased
(P < 0.05); however, there was no correlation between
expression of the five SSTR subtypes and other clinico-
pathological factors such as age, sex, tumor site, tumor
depth, distant metastasis.
Correlation between SSTR expression and proliferative
index and Bcl-2 or p53
The proliferative indexes in colorectal cancer cells with
negative expression of SSTR2 and SSTR3 were signifi-
cantly higher than that with positive expression(P < 0.05,
Table 3). A positive cytoplasmic immunoreactivity for
Bcl-2 was detected in 67 of 127 cases (52.8 %). The Bcl-2
expression in colorectal cancer cells with positive expres-
sion of SSTR1, 2, 3 ,5 were signifi cantly lower than that
with negative expression(P < 0.05, Table 3). In contrast,
nuclear accumulation of p53 was demonstrated in 81 of
127 cases (63.8 %). There was no correlation between fi ve
SSTR subtypes and p53 expression.
DISCUSSION
Five SSTR subtypes belong to G proteins family, and
different SSTR subtypes can be expressed in various
patterns in different normal tissues or tumors. Evaluation
of five SSTR subtypes expression in tumors may help
understand carcinogenesis, and progression of tumors,
as well as diagnosis and treatment. There are some co-
ntroversies on the dominant SSTR subtype and the co-
rrelation between five SSTR subtypes expression and
clinicopathological factors in colorectal cancer cells.
Buscail et al found that SSTR2 expression was lost in
colorectal cancer[3]. However, some subsequent studies
demonstrated that there was no difference between SSTR
subtypes expression between normal colorectal mucosae
and colorectal cancer[5-7]. Also some results indicated the
most frequent subtype was SSTR2 or SSTR5 in colorectal
cancer[3,6,8]. The expression of SSTR2 or SSTR5 was
signifi cantly lower in Dukes’ C and D stages of colorectal
cancer than that in Dukes’ A and B stages. The decrease
of SSTR2 or SSTR5 expression may be related to tumor
local invasion and metastasis, which may provide a growth
advantage in colorectal cancer. It is possible that SSTR2
or SSTR5 acts as a tumour suppressor[3,6]. But recent re-
search showed there was no correlation of SSTR mRNA
expression with Dukes’ stages[7].
In this study, only the frequency of SSTR4 expres-
sion in colorectal cancer cells was higher than that in the
colorectal mucosae. SSTR1 was expressed predominantly
in colorectal cancer cells, followed by SSTR5 and SSTR2.
There was no correlation between fi ve subtypes expression
and Dukes’ stages. The differences of our results from pre-
vious fi ndings may be accounted for by different research
methods. SSTR subtypes can express not only in colorectal
cancer cells but also in other constituents of cancer tissue,
such as vessels[9]. Thus, the PCR method tends to overes-
timate the real contribution of the various messengers for
receptors owing to the outstandingly sensitive technique,
and mRNA levels do not necessarily refl ect the presence
of the SSTR protein in certain cancers. To detect protein
expression of SSTR by receptor autoradiography can not
completely reflect protein levels of five SSTR subtypes,
because there are major differences in binding affi nity of
SSTA to various SSTR subtypes[1]. In addition, the discrep-
ancy may be relevant to different reagents and the small
sample size of our study. Cascade reaction induced by ac-
tivation of SSTR2 and SSTR5 can inhibit proliferation of
tumor cells. In our study, the expression of SSTR2, SSTR4
and SSTR5 reduced in poorly differentiated colorectal
cancer, and the SSTR3 and SSTR5 expression showed
a tendency to reduction with Dukes’ stages. The loss of
these receptors can weaken inhibition on the proliferation
of tumor cells, and may provide a growth advantage in
colorectal cancer. It suggests SSTR2, 3, 4, 5 may be related
to the development of colorectal cancer.
This study also demonstrated that the Ki-67 prolifera-
tive index in colorectal cancer cells with positive expres-
sion of SSTR2 or SSTR3 was significantly lower than
that with negative expression of SSTR2 or SSTR3. This
further proved that somatostatin in vivo can directly inhibit
colorectal cancer cell proliferation by activating SSTR2 and
SSTR3. The transplantable models of pancreatic primary
tumor and hepatic metastases were established in hamsters
which were xenografted with human pancreatic cancer cell
line transferred with the SSTR2 gene, and the following ef-
fects were induced: growth of tumors with SSTR2 positive
expression was delayed and the Ki-67 proliferative index
was decreased signifi cantly[10,11]. Activation of SSTR2 and
Table 1 SSTR expression in colorectal cancer
Tissue

n


SSTR1
Expression n (%)
SSTR2 SSTR3 SSTR4 SSTR5
Normal
mucosa
Colorectal 127
cancer
40 21(52.5) 16(40.0) 12(30.0) 1(2.5) 13(32.5)
52(64.6) 46(36.2) 24(18.9) 24(18.9)a 49(38.6)
aP< 0.05 vs normal mucosa.
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Qiu CZ et al. Somatostatin receptor subtype in colorectal cancer 2013

Page 4

SSTR3 can inhibit the proliferation of cancer cell through
the following mechanisms: SSTR2 and SSTR3 can inhibit
adenylate cyclase activity, which results in reduction of in-
tracellular cAMP concentration; they also can stimulate ty-
rosine phosphatase activity, modulate the mitogen activat-
ed protein kinases (MAPK) and upregulate the expression
of the cyclin-dependent kinase inhibitor p27Kip1 so that cell
cycle arrest is induced; the effects on K+ and Ca2+ chan-
nels lead to increased intracellular K+ concentration and
reduced intracellular Ca2+ concentration[12-15]. This study
further verifi ed that fi ve SSTR subtypes play different roles
in development of colorectal cancer. SSTR2 and SSTR3
can obviously inhibit the cell proliferation of colorectal
cancer and have an important effect on the progression of
colorectal cancer.
The activation of some SSTR subtypes not only directly
inhibits the proliferation of tumor cells, but also is rel-
evant to apoptosis. Bcl-2 is an apoptosis suppressor gene
and important parameter of apoptosis. In this study, Bcl-2
expression in colorectal cancer cells with positive expres-
sion of SSTR1, SSTR2, SSTR3 or SSTR5 significantly
decreased, indicating the four SSTR subtypes can promote
the apoptosis of tumor cells and affect the progression of
colorectal cancer by down-regulating the Bcl-2 expression
or counteracting the anti-apoptosis effect of Bcl-2. They
promote apoptosis via different mechanisms: Apoptosis is
mediated by SSTR1 via a block in the G1/S progression in
the cell cycle[16]. SSTR2 activation can promote apoptosis
through the following pathways, it sensitizes cancer cells
to apoptosis induced by tumor necrosis factor, induces
caspase-8 activation cascade, stimulates mitochondrial
cytochrome c released into the cytosol and downregulates
the Bcl-2 expression[17]. In the mouse models of pancreatic
primary tumor and hepatic metastases, which were xeno-
grafted with human pancreatic cancer cell line transferred
with the SSTR2 gene, it has been demonstrated that activa-
tion of caspase-3 and apoptotic index increased, expres-
sion of anti-apoptosis protein Bcl-2 decreased in tumor
cells expressing SSTR2[10,18]. Apoptosis can be signaled by
SSTR3 which can activate phosphoprotein phosphates and
lead to cellular acidifi cation and activation of acidic endo-
nuclease[19].
In conclusion, fi ve SSTR subtypes play different roles in
the development of colorectal cancer. SSTR2 and SSTR3
can inhibit the proliferation and promote apoptosis of tu-
mor cells. The expression of SSTR2, SSTR4 and SSTR5 is
correlated with malignant degree of colorectal cancer cells.
Though SSTR1 is the predominant SSTR subtype, its ex-

Table 2 Correlation between SSTR expression and clinicopathology in colorectal cancer
n (%)
Clinico-pathological factor n SSTR1 SSTR2 SSTR3 SSTR4 SSTR5
Sex

Age (yr)

Tumor site


Macroscopic type


Differentiation


Tumor depth

Lymph
node metastasis
Distant metastasis

Dukes’ stage







Male
Female
< 60
≥ 60
Right colon 31
Left colon 27
Rectum
Elevated 40
Ulcerative 59
Infi ltrative 28
Moderate 102
to well
Poor
Muscularis 24
Serosa
(+)
(-)
(+)
(-)
A
B
C
D
73
54
66
61
47(64.4)
35(64.8)
45(68.2)
37(60.7)
18(58.1)
17(63.0)
47(68.1)
27(67.5)
37(62.7)
18(64.3)
70(68.6)
26(35.6)
20(37.0)
20(30.3)
26(42.6)
11(35.5)
12(44.4)
23(33.3)
17(42.5)
13(22.0)a
16(57.1)
43(42.2)a
13(17.8)
11(20.4)
12(18.2)
12(19.7)
7(22.6)
5(18.5)
12(17.4)
10(25.0)
8(13.6)
6(21.4)
22(21.6)
13(17.8)
11(20.4)
12(18.2)
12(19.7)
6(19.4)
6(22.2)
12(17.4)
9(22.5)
8(13.6)
7(25.0)
24(23.5)a
28(38.4)
21(38.9)
24(36.4)
25(41.0)
11(35.5)
13(48.1)
25(36.2)
17(42.5)
21(35.6)
11(39.3)
46(45.1)a

69



25 12(48.0)
14(58.3)
68(66.0)
52(72.2)a 24(33.3)
30(54.5)
15(75.0)
67(62.6)
7(53.8)
22(55.0)
38(70.4)
15(75.0)
3(12.0)
11(45.8)
35(34.0)
2(8.0)
5(20.8)
19(18.4)
12(16.7)
12(21.8)
3(15.0)
21(19.6)
4(30.8)
8(20.0)
9(16.7)
3(15.0)
0(0.0)
3(12.5)
21(20.4)
15(20.8)
9(16.4)
2(10.0)
22(20.6)
2(15.4)
7(17.5)
13(24.1)
2(10.0)
3(12.0)
9(37.5)
40(38.8)
26(36.1)
23(41.8)
7(35.0)
42(39.3)
6(46.2)
16(40.0)
20(37.0)
7(35.0)


103
72
55
20
107
13
40
54
20
22(40.0)
6(30.0)
40(37.4)
5(38.5)
16(40.0)
19(35.2)
6(30.0)




aP < 0.05.
Table 3 Correlation between SSTR expression and proliferative
index, Bcl-2 or p53 expression



Ki67 proliferation Expression of Expression of
n index
mean±SD
Bcl-2 p53
positive (%) positive (%)
SSTR1 (+) 82
(-) 45
SSTR2 (+) 46
(-) 81
SSTR3 (+) 24
(-) 103
SSTR4 (+) 24
(-) 103
SSTR5 (+) 49
(-) 78
34.22 ± 24.33
40.21 ± 22.97
28.65 ± 18.80
40.71 ± 25.50a
25.72 ± 17.88
38.82 ± 24.55a
28.02 ± 20.12
38.29 ± 24.42
32.20 ± 21.92
38.95 ± 24.91
37(45.1)
30(66.7)a
15(32.6)
52(64.2)a
5(20.8)
62(60.2)a
9(37.5)
58(56.3)
17(34.7)
50(64.1)a
53(64.6)
28(62.2)
33(71.7)
48(51.3)
17(70.8)
64(62.1)
16(66.7)
65(63.1)
34(69.4)
47(60.3)
aP < 0.05.
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Page 5

S- Editor Pan BR L- Editor Zhu LH E- Editor Wu M
pression is correlated with lymph node metastasis. SSTA,
which has a high affi nity to SSTR2, SSTR3 and/or SSTR5
should be a treatment choice for patients with colorectal
carcinomas.
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Qiu CZ et al. Somatostatin receptor subtype in colorectal cancer 2015