Androgen receptor expression in endometrial carcinoma and its correlation with clinicopathologic features
Hashmi et al. BMC Res Notes
Androgen receptor expression in endometrial carcinoma and its correlation with clinicopathologic features
Atif Ali Hashmi 2
Zubaida Fida Hussain 2
Amna Qadri 1
Muhammad Irfan 2
Sahar Ramzan 2
Naveen Faridi 2
Amir Khan 0
Muhammad Muzzammil Edhi 3
0 Kandahar University , Kandahar 3802 , Afghanistan
1 Shaheed Zulfiqar Ali Institute of Science and Technology , Karachi , Pakistan
2 Liaquat National Hospital and Medical College , Karachi , Pakistan
3 Brown University , Providence, RI , USA
Objectives: Recent evidence suggests a role of androgen receptor expression as a prognostic and therapeutic biomarker in endometrial carcinoma, therefore in the present study we aimed to evaluate the frequency of androgen expression in different subtypes of endometrial carcinoma and its association with clinic-pathologic features. Results: 18/89 (20.2%) cases of endometrial carcinoma showed positive androgen receptor expression. On the other hand, low, moderate and high androgen receptor expression was noted in 7/89 (7.9%), 10/89 (11.2%) and 1/89 (1.1%) cases respectively. 15/77 (19.48%) of endometrioid cancers and 3/7 (42.28%) cases of serous carcinoma showed androgen receptor expression; while none of the cases of clear cell or carcinosarcoma revealed androgen receptor expression. No significant association of androgen receptor expression with various clinicopathologic features of endometrial carcinoma was noted. We found that a significant subset of endometrial cancers express androgen receptor especially a serous cancers; therefore we suggest that androgen receptor expression testing should be done in endometrial carcinoma.
Androgen receptor; Endometrial cancer; Endometrioid carcinoma; Serous carcinoma; Carcinosarcoma
Endometrial carcinoma (EC) is one of the most
common gynecological malignancies [
]. There are
various histologic subtypes of EC including endometrioid,
serous, clear cell, mucinous carcinoma and
carcinosarcoma. These have been historically categorized into two
major groups (type I and type II cancers) [
Endometrioid cancers are typically hormone (estrogen) driven
and they are strongly linked to estrogen exposure [
the other hand, recent evidence suggest that serous
cancers may also be associated with hormone exposure [
]. Progesterone and related compounds halts estrogen
driven proliferation and they can be used in the therapy
for low grade endometrioid cancers . Androgens also
display anti-proliferative effect in normal endometrium
and therefore can theoretically play a role similar to
]. Recent studies revealed that loss of androgen
receptor (AR) expression was found to be with poor
survival in EC [
]. On the other hand, AR expression may
serve as a potential therapeutic target in EC. Therefore,
in the present study we aimed to evaluate the expression
of AR in EC in our population and its association with
various clinic-pathologic parameters.
Total 103 cases of endometrial carcinoma were selected
from records of pathology department archives. All
patients underwent surgeries at Liaquat National
hospital, Karachi from January 2012 till December 2017 over
a period of 6 years. The study was approved by research
and ethical review committee of Liaquat National
Hospital and informed written consent was taken from all
patients at the time of surgery. Hematoxylin and eosin
stained slides and paraffin blocks were retrieved and new
sections were cut where necessary. Slides of all cases were
reviewed by two senior histopathologists and pathologic
characteristics like histologic type, tumor grade, T-stage,
lymphovascular invasion were evaluated. Moreover,
representative tissue blocks of 89 cases were available for AR
Androgen receptor IHC was performed using DAKO
EnVision method using monoclonal mouse anti-human
androgen receptor; clone AR441 according to
manufacturer’s protocol (dilution of 1:50). Nuclear staining
for AR was both quantitatively and qualitatively
evaluated. Hormone receptor IHC scoring was based on the
Liverpool endometrial steroid quick score with a final
score out of 12 calculated by multiplying the
proportion of positive tumor nuclei (1–10% = 1, 11–20% = 2,
21–40% = 3, > 40% = 4) by the staining intensity (0 = no
staining, 1 = weak, 2 = moderate, 3 = strong). Scores of
1–4 were characterized as low, scores of 5–8 were
considered moderate, and scores of 9–12 were classified as
high (Fig. 1).
Statistical package for social sciences (SPSS 21) was
used for data compilation and analysis. Mean and
standard deviation were calculated for quantitative variables.
Frequency and percentage were calculated for
qualitative variables. Fisher exact test was applied to determine
association. P value ≤ 0.05 was taken as significant.
Demographic patient’s profile
Table 1 shows demographic profile of patients. Mean age
of the patients was 56.34 years (+ 9.79). 81.6% patients
were post menopausal at the time of presentation. Most
common histologic subtype of EC was endometrioid
(87/103, 84.5%) followed by serous (9/103, 8.7%) and
a Androgen receptor Strong (3+)
b Androgen receptor Intermediate (2+)
c Androgen receptor weak (1+)
d Androgen receptor Nega ve (0)
of patients involved
carcinosarcoma (6/103, 5.8%). Most patients had more
than half of myometrial invasion (59/103, 57.3%), while
cervical invasion, adnexal involvement and nodal
metastasis was present in 26/103 (25.2%), 11/103 (10.7%) and
7/103 (6.8%) cases respectively. 89/103 (86.4%) cases
were at stage T1/T2 while 71/103 (68.9%) were
correspondingly at FIGO stage 1 (Table 1).
Androgen receptor expression in endometrial carcinoma
18/89 (20.2%) cases of EC showed positive AR
expression. On the other hand, low, moderate and high AR
expression was noted in 7/89 (7.9%), 10/89 (11.2%) and
1/89 (1.1%) cases respectively. 15/77 (19.48%) of
endometrioid cancers and 3/7 (42.28%) cases of serous carcinoma
showed AR expression; while none of the cases of clear
cell or carcinosarcoma revealed AR expression. No
significant association of AR expression with various
clinicopathologic features of EC was noted (Table 2).
In the present study, we aimed to evaluate the AR
expression in endometrial cancers and found that a
significant proportion of endometrial cancers especially
serous cancers exhibit AR expression, that may have
clinical and therapeutic significance.
Variable expression of AR was seen in previous studies.
Sasaki et al. reported 21% expression of AR [
]; on the
other hand, as high as 89% AR expression was detected
in another study [
]. Some studies reported degree of
differentiation/grade of EC to be inversely associated
with AR expression [
]; however, no such association
was noted in our study. In the prior studies most of the
work focused on endometrioid EC, as it seems to arise
as a result of hormonal drive. In a recent study, it was
noted that 70% of serous cancers and 50% of
carcinosarcoma also show AR expression and high levels of AR
expression was noted in half of serous carcinoma [
These findings correlate with results of our study as we
found 42.8% serous cancers to express AR, while high
AR expression was also noted in serous carcinoma. Some
studies also revealed association of AR expression with
good prognostic features and better disease free survival
]; however, we didn’t found any significant association
of AR expression with various pathologic parameters like
tumor stage and nodal metastasis.
From a clinical standpoint, it is important to know if
AR IHC expression can identify a subset of EC that can
benefit from anti-androgen therapy. Recent evidence
supports this speculation that androgen receptor
antagonism can be a therapeutic option in EC [
becomes especially important in high grade
endometrioid and serous cancers in which endocrine (ER/PR)
therapeutic option is not available. In our study we found a
high frequency of serous cancers to express AR.
One of the major limitations of our study was lack of
clinical follow up to elucidate AR expression with
disease free survival and low number of cases of
nonendometrioid cancer. Therefore, we suggest more large
scale studies with clinical follow up to identify role of
AR expression as prognostic marker in EC.
EC: endometrial carcinoma; AR: androgen receptor.
AAH and ZFH: main author of manuscript, have made substantial
contributions to conception and design of study. AQ, MI and SR: have been involved in
requisition of data. NF, AK and MME have been involved in analysis of the data
and revision of the manuscript. All authors revise the manuscript. All authors
read and approved the final manuscript.
We gratefully acknowledge all staff members of Pathology, Liaquat National
Hospital, Karachi, Pakistan for their help and cooperation.
The authors declare that they have no competing interests.
Availability of data and materials
Please contact author, Atif Ali Hashmi () for data
Consent to publish
Ethical approval and consent to participate
Ethics committee of Liaquat National Hospital, Karachi, Pakistan approved
the study. Written informed consent was obtained from the patients for the
There was no funding available for this manuscript.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
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