Research Article
The Importance of Galectin-3 and MUC1 in the Metastatic Spread of the Gastric Carcinoma
Nuket Ozkavruk Eliyatkin*1, Safiye Aktas2, Zehra Erkul3, Evrim Yalcın4, Erdem Comut5, Baha Zengel6 and Adam Uslu7
1Department of Pathology, Adnan Menderes University, Turkey
2Department of Oncology Safiye Aktas, , Dokuz Eylul University, Turkey
3Department of Pathology, Zehra Erkul, Turkish Ministry of Health-Izmir Bozyaka Training and Research Hospital, Turkey
4Department of Pathology, Evrim Yalcın, Turkish Ministry of Health-Van, Turkey
5Department of Pathology, Erdem Comut, Turkish Ministry of Health-Izmir Bozyaka Training and Research Hospital, Turkey
6Department of General Surgery, Baha Zengel, Turkish Ministry of Health-Izmir Bozyaka Training and Research Hospital, Turkey
7Department of General Surgery, Adam Uslu, Turkish Ministry of Health-Izmir Bozyaka Training and Research Hospital, Turkey
*Corresponding author: Nuket Ozkavruk Eliyatkin Department of Pathology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey
Published: 09 Jan, 2018
Cite this article as: Eliyatkin NO, Aktas S, Erkul Z, Yalcın
E, Comut E, Zengel B, et al. The
Importance of Galectin-3 and MUC1
in the Metastatic Spread of the Gastric
Carcinoma. Clin Oncol. 2018; 3: 1401.
Abstract
Objective: Gastric cancer mortality ranks forefront among cancer-related deaths. In order to be
able to decrease cancer-related deaths, many steps of carcinogenesis, and cancer biology should
be understood. It has been determined that MUC1 is a natural ligand of galectin-3 in cancer cells,
and binding of galectin-3 to MUC1 increases cell-surface polarization of MUC1 with a process
which might be related to the development of metastases. The purpose of his study is to evaluate
the association between the expressions of MUC1, and galectin-3 with other prognostic factors in
primary tumor, and synchronous lymph node metastasis of the primary tumor in patients diagnosed
as gastric carcinoma using immunohistochemical methods.
Material and Method: Samples of 125 primary gastric cancer, and synchronous lymph node
metastases of the primary tumor were evaluated as for the association between expressions of
galectin-3, and MUC1 with other prognostic parameters, and survival.
Results: Decrease in the expressions of galectin-3 and MUC1 in 105 cases with synchronous lymph
node metastases was detected relative to the primary tumor. Correlations were detected between
the level of galectin-3 expression, depth of tumoral invasion (p=0.015), and recurrence (p=0.002)
in the primary tumor, and also between galectin-3 expression, Lauren’s classification (p=0.028),
lymphovascular invasion (p=0.054), neural invasion (p=0.016), recurrence (p=0.005), and
metastasis (p=0.015) in the synchronous lymph node metastasis. In the primary tumor, correlations
were detected between the level of MUC1 expression, and Lauren’s classification (p=0.033), and
recurrence (p=0.033), and MUC1 expression, and Lauren’s classification (p=0.028), lymphovascular
invasion (p=0.054), neural invasion (p=0.016), and recurrence (p=0.005) in the synchronous lymph
node metastasis. In the primary tumor, and synchronous lymph node metastasis, any correlation
was not detected between the expressions of galectin-3, and MUC1, and survival in the primary
tumor, and also between the expression of galectin-3, and disease-free survival in the synchronous
lymph node metastasis. However in the primary tumor as the level of MUC1 expression increased
the probability of recurrence also increased (p=0.037). In the synchronous lymph node metastasis,
level of MUC1 expression did not affect DFS (p=0.189).
Conclusion: In the gastric carcinoma, and synchronous lymph node metastasis, individual
determination of galectin-3, and MUC1 expression levels, may be determinative factor as for the
pathobiological behavior of the gastric carcinoma, and its prognosis. However further studies which
will evaluate metastatic and/or recurrent tumoral tissue in addition to primary tumor tissue are
needed.
Keywords: Gastric carcinoma; MUC1; galectin-3; metastasis; prognosis
Introduction
Gastric carcinoma ranks 4. Among the most prevalently seen
cancer types in the world, and it is the second most frequent cause
of cancer-related mortalitty [1]. The steps of carcinogenesis in gastric
cancer, and biology of gastric cancer should be very well understood
in order to be able to decrease mortality rates, and develop new
successful and effective treatment strategies. The first step in the
progression of cancer is the degradation of extracellular matrix by the
release of tumor cells. Later on, at the critical stage of carcinogenesis,
metastases develop as disseminated tumor cells adhere to vascular
endothelium of distant organs. This process is thought to be
mediated via mechanical properties of cancer cells, and synchronous
specific expression of various adhesion molecules, and/or ligands
to enable them to attach to molecules on the surface of cancer, and
endothelial cells. Mucins are epithelial glycoproteins with heavy
molecular weight. Miscellaneous types of mucins have been defined.
They divide into two different groups based on their morphologic
structure, and functions as secreted type ve membrane-associated
type. Membrane-associated type mucins are associated with epithelial
cell-cell interactions. Mucin 1 (MUC1), is a bulky transmembrane
mucin protein of membrane-associated type which is expressed on
the apical surface of many secretory epithelial cells. In many cancer
types's 10-fold increase in MUC1 expression has been reported [2].
The association between this expression, and increased metastatic
potential, and worse prognosis has been described. Cancer-associated
MUC1 loses its apical membrane polarization, and it is expressed all
over the cell surface. Over expression of MUC1 inhibits E-cadherinrelated
cell-cell, and integrin-related cancer-matrix interactions,
and increases tumoral cell release from the area of primary tumor.
However galectin-3 is a galactoside-binding protein expressed by
many cell types. It may be found in the cell, and extracellular space,
associated with cell surface, and circulation. Extracellular galectin-3
bound to cell surface acts as an adhesion molecule during cell -cell
interaction, and it is associated with metastases. In various studies
performed on cell cultures, it has been determined that in human
cancer cells MUC1 is a natural ligand of galectin-3, and with binding
of galectin-3 to MUC1, surface polarization of MUC1 increases, and
this increase might be associated with the development of metastases
[3].
The purpose of this study is to evaluate the relationship between
MUC1, and galectin-3 expressions, and other prognostic parameters
in primary tumors, and synchronous lymph node metastases of the
tumor in patients diagnosed as gastric carcinoma in Izmir Bozyaka
Training and Research Hospital between the years 2003, and 2013.
Therefore, expressions of MUC1 and galectin-3 in cases with gastric
carcinoma may clarify molecular mechanism of metastasis, and
predict potential metastases which will occur later, and determine
the possibility of their becoming an important target agent in the
development of preventive treatment strategies.
Methods
Patients vs Tissue Samples
The study was approved by the Ethics Committee of Clinical
Researches of İzmir Bozyaka Training and Research Hospital.
The patients who were diagnosed as gastric carcinoma based on
histopathological examination of surgical resection materials
between the years 2003, and 2013 in Izmir Bozyaka Training and
Research Hospital were registered electronically. Archived H&E
stained preparations of the patients who had complete clinical, and
histopathological data, and received surgical, and chemotherapeutic
treatment modalities based on a standard procedure, then followed
up by the attending physician were re-evaluated. Archived tissue
blocks of lymph node metastases were chosen if adequate primary
tumor tissue and lymph node metastasis were available. Patients with
adequate tumor tissue, and paraffin blocks were included in the study.
Size, location, histological type of the tumor, depth of invasion, lymph
node metastasis, and perinodal invasion were evaluated. Besides,
lymphovascular invasion, neural invasion, lymphocytic response to
tumor and state of the serosal margins were evaluated. Histological
type of the tumor was determined based on WHO 2010 classification,
and other prevalently used Lauren’s classification (Figure 1). The
tumor stage was classified according to the 7th edition of the TNM
Classification of the International Union against Cancer (UICC).
Among the patients, 42 were females and 83 male. Their age ranged
from 29 to 91 years, with a mean age of 62.29 years. The average period
of postoperative follow-up period was 37, 79 months (0.23-182.01).
Tissue microarray (TMA)
H&E stained prepararions of the patients included in the
study which contained primary tumor tissue, and (if available)
representative tumoral areas for lymph node metastases were chosen
for sampling. From tumoral areas detected in archived paraffin blocks
of these selected preparations, 2 mm-diameter tissue cores per donor
block were punched out and transferred to a recipient block with a
maximum of 24 cores using a tissue microarrayer (Histopathology,
Japan). Thin sections (4 μm) were consecutively cut from the tissue
micro-arrays and transferred to polylysine-coated glass slides. H&E
staining was performed for confirmation of tumor tissue.
Immunohistochemistry
Immunostaining of Galectin-3 and MUC1was performed by
the streptavidin–biotin peroxidase method by tissue microarray.
Serial 5-μm sections were obtained, and these slides were baked
overnight at 60°C, dewaxed in xylene, and hydrated with distilled
water through decreasing concentrations of alcohol. All slides were
treated with heat-induced epitope retrieval in the microwave (in 10
mM/L citrate buffer, pH 6.0, for 40 min, followed by cooling at room
temperature for 20 min) and blocked for endogenous peroxidase and
biotin. Mouse anti-human Galectin-3 (Novo Castra, UK) and MUC-
1 (Novo Castra, UK) antibodies were used at 1: 100 dilutions to
detect the respective proteins, with anti-mouse Envison-PO (DAKO,
USA) as the secondary antibody. Binding was visualized with 3,
3’- diaminobenzidine (DAB) and counterstaining with Mayer’s
hematoxylin was performed to aid orientation. Immunoreactivity for
MUC1 was localized in the cytoplasm and membrane of the tumor
cells, while Gal-3 showed a cytoplasmic pattern. One hundred cells
were randomly selected and counted from five representative fields of
each section blindly by two independent observers (NE, ZE) and the
percentages of positive cells in the total counted were graded semiquantitatively
using a four-tier scoring system: negative (−), 0–5%;
weakly positive (+), 6–25%; moderately positive (++), 26–50%; and
strongly positive (+++), 51–100%. After, the levels of the expression
of MUC1, and galectin-3 were separated to two groups: low (negative
and weakly positive) expression and high (moderately positive and
strongly positive) expression.
Statistical analysis
The categorical variables were presented in a descriptive way
in tables containing absolute frequencies. Continuous variable of
normal distribution was described using the mean. Expression of gal-
3 and MUC1was assessed with various clinic-pathological parameters
using the χ2 test. Survival rates were calculated by the Kaplan-Meier
method. The difference between the survival curves was analyzed by
the log-rank test. Starting time was the day of surgical resection of
gastric cancer. Differences were considered significant when the P
value was less than 0.05.
Figure 1
Figure 2
Table 1
Table 1
Galectin-3 and MUC-1 expression in the primary tumor and the
synchronous lymph node metastasis.
Results
Galectin-3 and MUC1 expression in the primary tumor and
the lymph node metastasis of 125 patients with gastric cancer was
investigated by immunohistochemical analysis and the levels of the
expression of MUC1, and galectin-3 were separated to two groups:
low (negative ve weakly positive) expression and high (moderately
positive and strongly positive) expression as defined above (Figure
2-4) (Table 1).
In 105 cases with synchronous lymph node metastasis of
primary gastric carcinoma, galectin-3 levels of expression in primary
tumor, and its metastasis were compared, using dependent 2-group
nonparametric Wilcoxon Test, and a statistically significantly
difference was found between levels of expression (p=0.001 Wilcoxon
test) which demonstrated lower galectin-3 expression level in lymph
node metastasis relative to that in the primary tumor. A statistically
significant correlation was not found between the groups with
low, and high levels of galectin-3 expression (p=0.166). When we
compared the groups as for levels of MUC1 expression, a statistically
significant difference was detected between levels of expression
(p=0.0001 Wilcoxon test). Similar to the finding for galectin-3,
MUC1 expression levels in lymph node metastasis were lower than
those found in the primary tumor. However contrary to lack of
intergroup correlation for galectin-3 expression levels, a statistically
significant correlation was found between groups with lower, and
higher expression levels of MUC1 (p=0.005).
A statistically significant correlation was detected between
galectin-3 expression level in the primary tumor, and tumor invasion
depth (low –grade tumor T, and high-grade tumor T) (p=0.015), and
probability of recurrence (p=0.002). In cases of synchronous lymph
node metastasis, a statistically significant correlation was detected
between galectin-3 expression, and Lauren’s classification (p=0.028),
lymphovascular invasion (p=0.054), neural invasion (p=0.016),
probability of recurrence (p=0.005), and incidence of metastasis
(p=0.015) (Table 2).
In cases of primary tumor, a statistically significant correlation was
detected between MUC1 expression level, and Lauren’s classification
(p=0.033), and recurrence (p=0.033). In cases of synchronous lymph
node metastasis a statistically significant correlation was found
between MUC1 expression and Lauren’s classification (p=0.028),
lymphovascular invasion (p=0.054), neural invasion (p=0.016), and
likelihood of recurrence (p=0.005) (Table 3).
In Pearson correlation analysis the correlation between age, and
disease-free survival (DFS), and overall survival (OS) was evaluated.
In patients younger than 60 years, median DFS, and OS were found as
43.94, and 45.94 months, respectively. However in patients older than
60 years, DFS, and OS were 28.85, and 30.95 months, respectively
which might be related to increased DFS, and OS in patients aged
more than 60 years.
Patients with improved OS rate as detected in Kaplan-Meier
analysis, and lower galectin-3 expression in primary tumor tissue
as assessed by Log-Rank test, had a higher quality of life without
any statistically significant intergroup difference (p=0.071). In the
group with synchronous lymph node metastasis lower, or higher
galectin-3 expression levels did not apparently effect overall survival
rates (p=0.637). The 0-0.5 % of the patients who had negative (-)
galectin-3 expression in the primary tumor tissue, had a worse
disease progression, while at higher expression levels more improved
disease progression was detected. (p=0.053). However in 51-100 %
of the cases with strongly positive (+++), galectin-3 expression had
a worse prognosis. A significant difference was not detected as for
overall survival rates between groups with lower, and higher MUC1
expression levels in the primary tumor tissue (p=0.801). However,
disease progression worsened as MUC1 expression levels in the
primary tumor tissue increased. (p=0.048). MUC1 expression levels
in the synchronous lymph node metastasis did not affect prognosis
(p=0.220). Besides, grouping based on lower, and higher MUC1
expression levels had not any significance with respect to prognosis.
(p=0.687).
In Kaplan-Meier analysis of DFS using log-rank test, galectin-3
expression level (-, +, ++, +++) in the primary tumor tissue was
not statistically significant (p=0.050). Patients lower galectin-3
expression levels had a higher quality of life, albeit lack of any
significant difference. A significant difference was not detected
between groups with lower, and higher galectin-3 expression levels
regarding prognosis (p=0.068). Galectin-3 expression levels (-, +, ++,
+++) in the synchronous lymph node metastases did not affect DFS
(p=0.836). Higher, and lower galectin-3 expression levels also had not
any prognostic significance (p=0.548). Increases in MUC1 expression
in the primary tumor was associated with higher recurrence rates
(p=0.037) (Figure 5). Besides, lower, and higher MUC1 expression
levels had not any impact on DFS (p=0.937). MUC1 expression levels
in the synchronous lymph node metastasis also did not affect DFS
(p=0.189) (Figure 6). Lower, and higher expression levels had not any
significance for DFS (p=0.714).
Figure 3
Table 2
Table 2
Relation between Galectin-3 expression and clinicopathological features in the primary tumor and the synchronous lymph node metastasis.
Table 3
Table 3
Relation between MUC-1 expression and clinicopathological features in the primary tumor and the synchronous lymph node metastasis.
Discussion
In this study, in a patient group diagnosed as gastric carcinoma
the correlation between expressions of galectin-3, and MUC1 in the
primary tumor, and its synchronous lymph node metastasis with
other prognostic parameters and their impact on DFS, and OS were
investigated. In various cancer types, expressions of galectin-3 and
MUC1 have been investigated in only primary tumor tissue, and
diverse outcomes have been reported. In some studies, comparisons
have been made also with adjacent non-tumoral tissue. In a study
where levels of galectin-3 were evaluated in cell line, gastric carcinoma,
and adjacent non-tumoral tissue, the association between decreased
galectin-3 expression and presence of distant metastasis, and in vitro
higher invasive phenotype was determined [4]. In our study level of
galectin-3 expression level was analyzed in terms of recurrence, and
metastasis, and significantly decreased galectin-3 levels were observed
in synchronous lymph node metastasis when compared with the
primary tumor. Okada et al. detected higher galectin-3 expression
levels in cancer tissue when compared with normal tissue. However
in the same study the authors concluded that decreased galectin-3
expression in the tumor tissue was associated with poor prognosis
characterized by lymph node metastasis, advanced stage, and/or
poorly differentiated tumor [5]. However detected that decreased
galectin-3 expression in cases of pancreas ductal adenocarcinoma was
associated with advanced stage, and increased number of lymph node
metastases [6]. In another study, increased galectin-3 expression had
been correlated with poorly differentiated carcinoma, and tumor
progression [7]. This outcome was not in accordance with our study
findings. Where as in the literature controversial outcomes have
been indicated about clinicopathological significance of galectin-3
expression of patients with colorectal, gastric, ovarian, oral cavity or
thyroid cancers [8-12]. Immunohistochemical evaluation galectin-3
expression in 57 samples of gastric cancer tissue, galectin-3 was
determined as an unreliable biomarker of prognosis [13]. However in
this study, galectin-3 expression was scored in only two subgroups as
follows: 1 (negative or weak), no staining or less than 50 % of tumour
cells are stained, and 2 (moderate or strong) when ≥50 % of the
tumour cells are stained. Besides cytoplasmic and/or nuclear staining
were/was considered as positive reaction. As is the case with many
studies, we also evaluated only cytoplasmic/membranous staining
as an evidence of positivity, and we didn’t take nuclear staining
into consideration which might account for our diverse outcomes.
In some studies it has been demonstrated that apart from galectin-3
expression levels, its localization patterns also play a role in cancer
progression [14]. Found that nuclear galectin-3 immunoreactivity is
significantly stronger in the diffuse type tumors relative to intestinal
type tumors [9]. Though the role of galectin-3 in carcinogenesis has
not been fully defined yet, cellular localization of galectin-3 may
indeed play an important role in malignant transformation. One of
the probable mechanisms may be related to the regulation of signal
pathways [15]. Galectin-3 is down regulated by tumor suppressor
gene p53 [16]. Besides, antiapoptotic activity of galectin-3 has been
demonstrated [15].
In the literature, some studies have evaluated serum galectin-3
levels using ELISA method. Cheng et al. found significantly higher
galectin-3 levels in patients with gastric cancer when compared with
cases with benign gastric diseases, and healthy controls. They also
concluded that serum galectin-3 levels were associated with lymph
node metastasis (p=0.001), and distant metastasis (p<0.001) [17].
However its use as a screening test seems to require conduction of
larger series.
Increased levels of MUC1 in various cancer types have been
described [18-19]. MUC1, acts as an anti-adhesion molecule, and
facilitates release of tumor cells from tumoral tissues in malignancies.
In malignant cells increased levels of MUC1 expression may suppress
extracellular domains, increase survival times of tumor cells, and
induce development of invasion, and metastasis. Similarly, in a study
where MUC1 expression was evaluated using tissue microarray
method, higher MUC1 expression levels were detected in gastric
carcinoma when compared with non-tumoral gastric mucosa, and
positive correlation was demonstrated between UICC staging,
depth of invasion, lymphatic, and venous invasion, and lymph node
metastasis [20]. In the study depth of invasion was defined as Tis-T1,
and T2-T4, while UICC staging was described as 0-1, and 2-4, however
in our study depth of invasion was found as T1-T2, and T3-T4, while
UICC stages were grouped as 1-2, and 3-4. Therefore, we thought that
different outcomes might be obtained from other studies. However, in
this study where Lauren’s classification was performed based on the
criteria similar to ours, comparable relevant outcomes were obtained
(p=0.002) also acquired similar results [21]. However Wang et al. [22]
and Kocer et al. [23], could not detect any difference between these
diffuse and intestinal types of carcinoma as for MUC1 expression
[22-23]. This discordance might stem from scarce number of study
participants or heterogeneity of the study population. In our study
decreased overall survival rates were observed as the level of MUC1
expression increased (p=0.048). In a study where the state of MUC1,
and MUC4 expressions were evaluated in early stage gastric cancer,
higher levels of MUC1 expression were detected in well-differentiated
tumors. As a concluding remark the authors stated that MUC1 was
correlated with lymph vascular invasion without any association
with survival rates. Since this study population consisted of only
early-stage gastric cancer patients, according to their interpretation
MUC1 was not associated with survival rates [24]. The same research
team performed a study on advanced-stage gastric cancer patients,
detected higher MUC1 expression levels in well-differentiated gastric
adenocarcinoma which might affect survival rates [25]. In our study,
most of the patients were in advanced stage, and OS decreased
as expression levels of MUC1 increased in primary tumor tissue
(p=0.048). Since when we grouped patients as those with lower, and
higher MUC1 expression levels, we couldn’t detect any significant
intergroup difference as for OS (p=0.801) we thought that numerical
evaluation (ie. Ki-67 proliferation index) of MUC1 expression might
be more meaningful. MUC1 expression levels in synchronous lymph
node metastases did not affect prognosis. Increased likelihood of
recurrence in line with increased MUC1 expression levels in the
primary tumor (p=0.037) suggest that MUC1 expression might be an
important determinant of DFS. However as a striking finding, levels
of MUC1 expression in the synchronous lymph node metastasis did
not influence DFS (p=0.189). In our study MUC1 expression was
evaluated both in the primary tumor, and synchronous lymph node.
Since we haven’t encountered similar type of study in our literature
review, conduction of comparable studies should be performed.
In normal tissues MUC1 acts as a preventive barrier. However
in neoplastic tissues MUC1 is underglycosylated, and in normal cells
their suppressed epitopes are disclosed. This characteristic feature
transforms tumor-related MUC1 into a target molecule by means
of a process mediated by antibodies, toxins or radionucletides or it
allows discovery of a vaccine which targets tumor-related MUC1
[26]. Crucial role of over expression of tumor-related MUC1 in the
metastasis, and progression of epithelial ovarian cancer has been
reported, and thus it has been considered as an ideal treatment target
in the control of metastasis, and recurrence [26]. Increased MUC1
expression is associated with invasion, and metastasis. Especially,
extracellular domain promotes progression of cancer, and it is
effective like an ant adhesion molecule. It also induces detachment
of tumor cells from tumor tissue, and causes formation of micro
metastases.
In a meta-analysis of 23 different studies consisting of 3245
cases, the prognostic importance of MUC1 in various carcinomas
(cholangiocarcinoma, breast carcinoma, colorectal carcinoma
gallbladder carcinoma, and gastric carcinoma) was evaluated, and
negative predictive value of positive MUC1 staining for OS was
detected. In subgroup analysis of the gastric cancer patients, the
increased MUC1 expression was found to be more effective on OS
compared to other groups [27]. In their in vitro studies, Zhao et al,
demonstrated that interaction between cancer cells which express
galectin-3, and MUC1 in the circulation (cells carrying galectin-3
ligand TF) promoted development of metastases. They also displayed
that galectin-3 disrupts protective shield of the cell surface [28].
Figure 4
Figure 5
Figure 5
Kaplan–Meier curve of disease-free survival of patients according
to MUC1 expression levels in the primary tumor tissue (p=0.037).
Figure 6
Figure 6
Kaplan–Meier curve of disease-free survival of patients according
to MUC1 expression levels in the synchronous lymph node metastasis
(p=0.189).
According to the Results of the Present Study
In gastric carcinoma, when galectin-3, and MUC1 expression
levels in the primary tissue, and synchronous lymph node metastasis
were grouped in four separate scores, lower levels of galectin-3, and
MUC1 expression were detected in the metastatic tissue. Whereas,
when categorized as groups with lower, and higher expression levels,
since only MUC1 expression levels were statistically significantly
different, we thought that evaluation of immune expression should
be made and indicated numerically as percentages would be more
meaningful rather than in groups of lower, and higher expression
levels.
In the group where galectin-3 expression was negative (-) in the
primary tumor tissues of 0-5 % of the patients, decreased overall
survival times were detected, while OS times decreased as MUC1
expression levels increased in the primary tumor tissue. Levels of
MU1 expression in the synchronous lymph node metastases did
not affect prognosis. Cases with lower galectin-3 expression in the
primary tumor tissue had longer disease-free survival times, without
any statistically significant intergroup difference. Level of galectin-3
expression in the synchronous lymph node metastases did not
affect DFS. As the level of MUC1 increases in the primary tumor,
probability of recurrence also increases. However, MUC1 expression
levels in the synchronous lymph node metastases did not affect DFS.
A correlation existed between MUC1 expression in primary tumor
tissue and synchronous lymph tissue and recurrence rates.
In this study, in cases with gastric carcinoma determination of
galectin-3, and MUC1 expression levels in the primary tumor tissue,
and its synchronous lymph node metastasis separately, may play a
determinative role in the pathobiologic behavior, and prognosis of
gastric carcinoma Nonetheless, further studies which will evaluate
these biomarkers both in the metastatic, and/or recurrent tumor
tissue in addition to the primary tumor tissue are needed.
References
- Bosman T, Carneiro F, Hruban RH, Theise ND. World Health Organization Classification of Tumours of the Digestive System. 4th Edition. Lyon, France: IARC Press; 2010.
- Zhao Q, Guo X, Nash GB, Philip C. Stone, John Hilkens, Jonathan M. Rhodes, et al. Circulating galectin-3 promotes metastasis by modifying MUC1 localization on cancer cell surface. Cancer Res 2009;69(17):6799-806.
- Zhao Q, Barclay M, Hilkens J,Xiuli Gou, Hannah Barrow, jonathan M Rhodes, et al. Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis. Cancer. 2010;9:154.
- Leal MF, Calcagno DQ, Chung J, de Freitas VM, Demachki S, Assumpção PP, et al. Deregulated expression of annexin-A2 and galectin-3 is associated with metastasis in gastric cancer patients. Clin Exp Med. 2015;15(3):415-20.
- Okada K, Shimura T, Suehiro T, Mochiki E, Kuwano H. Reduced galectin-3 expression is an indicator of unfavorable prognosis in gastric cancer. Anticancer Res. 2006;26(2B):1369-76.
- Shimamura T, Sakamoto M, Ino Y, Shimada K, Kosuge T, Sato Y, et al. Clinico-pathological significance of galectin-3 expression in ductal adenocarcinoma of the pancreas. Clin Cancer Res. 2002;8(8):2570-5.
- Miyazaki J, Hokari R, Kato S, Tsuzuki Y, Kawaguchi A, Nagao S, et al. Increased expression of galectin-3 in primary gastric cancer and the metastatic lymph nodes. Oncol Rep. 2002;9(6):1307-12.
- Endo K, Kohnoe S, Tsujita E, Watanabe A, Nakashima H, Baba H, et al. Galectin-3 expression is a potent prognostic marker in colorectal cancer. Anticancer Res. 2005;25(4):3117-21.
- Baldus SE, Zirbes TK, Weingarten M, Fromm S, Glossmann J, Hanisch FG, et al. Increased galectin-3 expression in gastric cancer: correlations with histopathological subtypes, galactosylated antigens and tumor cell proliferation. Tumour Biol. 2000;21(5):258-66.
- van den Brule FA, Berchuck A, Liu FT, Gillet C, Sobel ME, et al. Differential expression of the 67-kD laminin receptor and 31-kD human laminin-binding protein in human ovarian carcinomas. Eur J Cancer. 1994;30A(8):1096-9.
- Mesquita JA, Queiroz LM, Silveira ÉJ, et al. Association of immunoexpression of the galectins-3 and -7 with histopathological and clinical parameters in oral squamous cell carcinoma in young patients. Eur Arch Otorhinolaryngol. 2016;273(1):237-43.
- Selemetjev SA, Savin SB, Paunovic IR, Tatic SB and Cvejic D. Changes in the expression pattern of apoptotic molecules (galectin-3, Bcl-2, Bax, survivin) during progression of thyroid malignancy and their clinical significance. Wien Klin Wochenschr. 2015;127(9-10):337-44.
- Gomes TS, Oshima CT, Forones NM, De Oliveira Lima F and Ribeiro DA. Expression of galectin-3 in gastric adenocarcinoma. Indian J Med Res. 2014;140(1):69-76.
- Califice S, Castronovo V, Bracke M and van den Brule F. Dual activities of galectin-3 in human prostate cancer: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3. Oncogene. 2004;23(45):7527-36.
- Liu FT and Rabinovich GA. Galectins as modulators of tumour progression. Nat Rev Cancer 2005;5:29-41.
- Raimond J, Rouleux F, Monsigny M and Legrand A. The second intron of the human galectin-3 gene has a strong promoter activity down-regulated by p53. FEBS lett. 1995;363(1-2):165-9.
- Cheng D, Liang B and Li Y. Serum galectin-3 as a potential marker for gastric cancer. Med Sci Monit. 2015;21:755-60.
- Levi E, Klimstra DS, Andea A, Basturk O and Adsay NV. MUC1 and MUC2 in pancreatic neoplasia. J Clin Pathol. 2004;57(5):456-62.
- Rakha EA, Boyce RW, Abd El-Rehim D, Kurien T, Green AR, Paish EC, et al. Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod Pathol. 2005;18(10):1295-304.
- Li XH, Zheng HC, Wang ZG, Takahashi H, Yang XH, Guan YF, et al. The clinicopathological and prognostic significance of MUC-1 expression in Japanese gastric carcinomas: an immunohistochemical study of tissue microarrays. Anticancer Res. 2008;28(2A):1061-7.
- Baldus SE, Zirbes TK, Engel S, Hanisch FG, Mönig SP, Lorenzen J, et al. Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas. Int J Cancer. 1998;79(2):133-8.
- Wang RQ and Fang DC. Alterations of MUC1 and MUC3 expression in gastric carcinoma: relevance to patient clinicopathological features. J Clin Pathol. 2003;56(5):378-84.
- Kocer B, Soran A, Kiyak G, Erdogan S, Eroglu A, Bozkurt B, et al. Prognostic significance of mucin expression in gastric carcinoma. Dig Dis Sci. 2004;49(6):954-64.
- Tamura Y, Higashi M, Kitamoto S, Yokoyama S, Osako M, Horinouchi M, et al. MUC4 and MUC1 Expression in Adenocarcinoma of the Stomach Correlates with Vessel Invasion and Lymph Node Metastasis: An Immunohistochemical Study of Early Gastric Cancer. PLOS ONE. 2012;7(11):e49251.
- Utsunomiya T, Yonezawa S, Sakamoto H, Kitamura H, Hokita S, Aiko T, et al. Expression of MUC1 and MUC2 mucins in gastric carcinomas: its relationship with the prognosis of the patients. Clin Cancer Res. 1998;4(11):2605-14.
- Deng J, Wang L, Chen H, Li L, Ma Y, Ni J, Li Y. The role of tumour-associated MUC1 in epithelial ovarian cancer metastasis and progression. Cancer Metastasis Rev. 2013;32(3-4):535-51.
- Xu F, Liu F, Zhao H, An G and Feng G. Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers: A Meta-Analysis. Medicine (Baltimore). 2015;94(50):e2286.
- Zhao Q, Guo X, Nash GB, Stone PC, Hilkens J, Rhodes JM, et al. Circulating galectin-3 promotes metastasis by modifying MUC1 localization on cancer cell surface. Cancer Res. 2009;69(17):6799-806.