Original Article
EXPRESSION
OF
E-CADHERIN
IN
DIFFERENT
MUCOEPIDERMOID CARCINOMA OF SALIVARY GLANDS
GRADES
OF
Saadia Muneer1, Shoaib Naiyer Hashmi2, Rabia Ahmed2
1
Islamabad Medical and Dental Hospital, Bharakahu, Islamabad, Pakistan
Armed Forces Institute of Pathology (National University of Medical Sciences), Rawalpindi, Pakistan
2
ABSTRACT
Objective: To determine the expression of E-cadherin in mucoepidermoid carcinoma (MEC) and to find out its
association with different histological grades.
Study design: Descriptive study.
Materials and Methods: This is a descriptive study. A total of 30 cases of MEC were taken. Data was extracted
from clinical histories. After grading on the basis of system described by Auclair et al. and Goode, E-cadherin was
applied according to standard protocol. Final results were analysed. Chi-square test was applied to find out the
association of E-cadherin with different histological grades of MEC. p-value <0.05 was considered significant.
Results: E-cadherin showed positive results in 17 cases and altered (reduced positive or negative) in 13 cases.
Among low grade tumors 10 out of 14 were strongly positive while on the other hand only 4 out of 10 showed
positive results in high grade tumors. p-value for E-cadherin was calculated to be 0.289.
Conclusion: E-cadherin showed a slight loss of expression with increase in grade of tumor but this association of
marker with different grades of tumor was found to be insignificant.
Keywords: Mucoepidermoid carcinoma (MEC), E-cadherin, Salivary Glands.
This article can be sited as: Muneer S, Hashmi SN, Ahmed R. Expression of e-cadherin in different grades
of mucoepidermoid carcinoma of salivary glands. Pak J Pathol. 2016: 27(2): 85-89.
INTRODUCTION
(CDH1) is mostly found in the adherin junctions
Mucoepidermoid carcinoma (MEC) is the
between the cells of epithelium and has a vital role in
most common malignant tumor of the major and
maintaining the normal shape of epithelial tissue [10].
minor salivary glands. In Pakistan MEC is reported to
The dysfunction in cell-cell adhesion may lead to
be around 9.5-25.6% while an overall prevalence of
reduced expression of E-cadherin. Most tumors have
12-40% has been found worldwide [1-4]. The ductal
abnormal cellular architecture and local invasion
cells of salivary glands are believed to give rise to
comes with loss of tissue integrity. E-cadherin is
MEC and they have the ability to produce 3 different
known as tumor suppressor gene because there is
cell types: mucous cells, intermediate cells, and
loss of expression of E-cadherin protein with
epidermoid cells. Growth patterns range from cystic
increased invasiveness and metastasis of tumor [11].
to solid to infiltrative. These parameters have been
Loss of E-cadherin expression is found frequently in
incorporated into several different grading systems
many types
[3, 5]. Auclair et al (1992) and Goode et al (1998)
mucoepidermoid carcinoma [12].
of
human malignancies, including
described a grading system for MEC. This system
divides the tumor into 3 grades on the basis of some
specific histological features [6-8].
E-cadherin belongs to a large family of genes
MATERIAL AND METHODS
In
this
mucoepidermoid
descriptive
study
carcinoma
30
were
cases
of
included.
that code for calcium-dependent cell adhesion
Histological grading was done according to the
molecules. There are more than eighty members of
criteria proposed by Auclair et al and Goode et al.
the cadherin superfamily [9]. The E-cadherin gene
This system divides the tumor into 3 grades, low,
intermediate and high grade on the basis of
Correspondence: Dr Saadia Muneer, 17-C Askari 3, Chaklala
Scheme 3. Rawalpindi, Pakistan
Email: [email protected]
intracystic component, neural invasion, necrosis,
Received: 12 Feb 2016-; Revised: 14 Apr 2016-; Accepted: 16 Jun 2016
Pakistan Journal of Pathology 2016; Vol. 27 (2): 85-89.
85
Expression of E-cadherin in different grades of mucoepidermoid carcinoma of salivary glands
abnormal mitosis and anaplasia [13]. Tissue sections
Immunohistochemical labeling pattern: In
were prepared according to the standard protocol.
MEC variable staining pattern was found from case to
Necrosed, scarce and poorly oriented tissues were
case. Mostly it was found in cell membrane and
excluded. According to this system 14 were found to
cytoplasm. E-cadherin was applied to all 30 cases of
be low grade, 6 were intermediate grade and 10 were
which 17 (56.67%) showed more than 90% of
high grade tumors. Immunostaining for e-cadherin
staining and were positive (++), 9(30%) showed
was based on the criteria proposed by Sheih et al
between 10-90% staining and were weak positive (+)
(Table 1) [12]. Non-neural epithelial tissue was used
and only 4 (13.34%) were found to be negative (-).
as positive internal control. When more than 90% of
When we sorted these results with different grades of
tumor cells were stained uniformly at same intensity,
tumors we found that out of 14 cases of low grade
results were taken as positive (++). When the
tumors 10 were strongly positive (++), 3 were weak
labeling of neoplastic cells was weaker and between
positive (+) and only 1 case was negative. In
10%-90%, the results were defined as reduced
intermediate grade tumors 50% of the cases i.e. 3
expression (+). When no labeling was observed or it
were strongly positive and 3 were weak positive (+).
was less than 10%, the results were classified as
Among the 10 high grade tumors,4 were strongly
negative (-). For statistical analysis, cases that
positive (++), 3 were weak positive (+) and 3 were
showed a positive labeling pattern were considered
negative (-) (Table-2).
as normal, whereas the other 2 patterns (negative
According to statistical analysis the criteria
and reduced) were classified as altered. Chi-square
made for E-cadherin scoring (table-1), 17 cases were
test was used to find out the association of e-
positive and 13 cases were scored as altered in a
cadherin with different grades of tumor. P value ≥
total of 30 cases. Among the 14 low grade cases, 10
0.05 was taken as significant.
were positive and 4 had altered expression of Ecadherin. From the 6 intermediate grade cases, the
RESULTS
results were 50% in each category. In the 10 high
Clinicopathological characteristics: In the
grade cases 4 were positive (Table-3, Figures 1-3).
present study, out of a total of 30 patients, 21 were
males and 9 were females. According to the
anatomical location 18 were found to be from parotid
region which is the most common site. The mean age
range of patients was 47.6±18.6 years.
Table-1: Mucoepidermoid carcinomas- Auclaier et al grading system
Grade
Score
Low
0-4
Intermediate
5-6
High
7-14
Table-2: E-cadherin expression in different grades of tumor.
Grade
>90% (++)
10-90% (+)
<10% (-)
Total
Low
10 (71.4%)
3 (21.4%)
1 (7.1%)
14
Pakistan Journal of Pathology 2016; Vol. 27 (2): 85-89.
86
Expression of E-cadherin in different grades of mucoepidermoid carcinoma of salivary glands
Intermediate
3 (50%)
3 (50%)
0 (0%)
6
High
4 (40%)
3 (30%)
3 (30%)
10
Total
17 (56.67%)
9 (30%)
4 (13.34%)
30
Table-3: Expression of E-cadherin according to criteria used for Statistical Analysis
Grade
E-Cadherin
Positive
Altered
Low Grade
10 (71.42%)
4 (28.58%)
14
Intermediate Grade
3 (50%)
3 (50%)
6
High Grade
4 (40%)
6 (60%)
10
Total
17 (56.67%)
13 (43.33%)
30
Total
The suppression of E-cadherin expression is
regarded as an event liable for dysfunction in cell
adhesion. Loss of e-cadherin expression is found
frequently in many types of human malignancies like
oral squamous cell carcinoma, odontogenic tumors,
soft tissue sarcomas, prostate cancer, breast cancer,
colorectal cancer and also in mucoepidermoid
Figure-1: MEC – Low Grade showing mucous
cells and cystic spaces (H and E stain, 10x100
magnifications)
carcinoma [11,12].
In
the
present
study
30
cases
of
mucoepidermoid carcinoma were taken in total.
Among the 14 low grade tumors 10(71%) were
positive and 4 had altered results. In 6 of the
intermediate grade tumors 3(50%) were positive and
3 were altered while in the 10 high grade tumors only
4(40%) were positive and 6 showed altered results.
According to present study a mild to moderate
Figure-2: Education status of the patients
n=157).
decrease is seen in the expression of E-cadherin with
the increase in MEC grade. Decrease in expression
of e-cadherin in many tumors is associated with
invasion and metastasis but this reduced expression
is not very significant in MEC as compared to other
tumors of the body.
Very few studies are available concerning
the expression of E-cadherin on MEC. In a study by
Figure-3: Low grade MEC showing positive (++)
E-cadherin membrane staining in tumor cells (E
Cadherin immunohistochemical stain, 40x100
magnifications.
Tsubochi et al, out of 7 patients of MEC, 6 showed
normal result and 1 showed abnormal expression of
E-cadherin [14]. On the other hand, Shieh et al,
proposed
DISCUSSION
through
their
study
that
abnormal
expression of this marker occur in majority of the
MEC cases [12].
Pakistan Journal of Pathology 2016; Vol. 27 (2): 85-89.
87
Expression of E-cadherin in different grades of mucoepidermoid carcinoma of salivary glands
In a study performed by Furuse et al,
membrane expression of E-cadherin was found in all
E-cadherin may not be a very strong marker
in case of MEC.
the benign and malignant salivary gland tumors [15].
In 2000, Economopoulou et al commented in their
study that no focal expression of the marker was
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