Oxytocin receptor expression is associated with estrogen receptor status in breast tumors

2021 ◽  
Vol 67 (4) ◽  
pp. 360-365
Author(s):  
T.S. Kalinina ◽  
V.V. Kononchuk ◽  
S.V. Sidorov ◽  
D.A. Obukhova ◽  
G.R. Abdullin ◽  
...  

The oxytocin receptor (OXTR) plays an important role in childbirth, breastfeeding, and social interactions. There is emerging evidence that OXTR is associated with the breast cancer (BC) initiation and progression. However, the mechanisms leading to a change in its expression, the diagnostic or prognostic value of the receptor in BC are currently poorly understood. Here, we have evaluated the relative level of OXTR expression in BC samples (n=107), and also investigated the effect of estradiol on its expression in MCF-7 and MDA-MB-231 cells. The level of OXTR expression was significantly lower in breast tumor tissue than in normal tissue obtained from the same patient. The expression of OXTR was dependent on the status and expression of the estrogen receptor (ER): the level of OXTR mRNA was significantly lower in ER-negative BC samples compared to ER-positive BC samples. Moreover, OXTR expression was also lower in samples from patients with luminal subtype with a low value of ER expression (0-5 score according to the IHC assay, Allred scoring) compared with samples with high ER expression (6-8 score). In luminal BC, OXTR expression was associated with the HER2 expression level: the OXTR mRNA level was higher in tumors with a HER2 IHC score of 1+ as compared to cases with the HER2 expression score of 2+, 3+. We also showed that estradiol increased the level of OXTR mRNA in MCF-7 cells, but not in ER-negative MDA-MB-231 cells. These data indicate that changes in OXTR expression in BC tissues can be caused by increased ER expression. We found no association between OXTR and T or N stages and progesterone receptor expression.

1988 ◽  
Vol 24 (3) ◽  
pp. 385-390 ◽  
Author(s):  
Liviana Madeddu ◽  
Nicole Legros ◽  
Nicole Devleeschouwer ◽  
Carine Bosman ◽  
Martine J. Piccart ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21035-e21035
Author(s):  
Yoko Tani ◽  
Yasuhiro Koh ◽  
Akihiro Tamiya ◽  
Shun-ichi Isa ◽  
Akihito Kubo ◽  
...  

e21035 Background: The role of estrogen receptor status in the carcinogenesis of lung cancer remains elusive. A census of clonal and sub-clonal mutations has been defined through the analyses of evolutionary histories of cancers. We previously reported a prospective multicenter molecular epidemiology study (JME study; Kawaguchi T, J Clin Oncol 2016), which included the expression levels of estrogen receptors β (ER) using immunohistochemistry(IHC) and the mutational profile using next generation sequencing as well as solid smoking information and reproductive/ hormonal risk factors from the detailed questionnaire. Methods: Utilizing the data of the JME study, the impact of ER in lung cancer development was explored. All the patients underwent surgery. In 441 ever- and 435 never-smokers, ER were observed in 46.4% and 53.5%, respectively. The cancer-associated 72 gene mutations and 5 gene amplifications examined in this study included EGFR, SMAD4, APC, FBXW7, BRAF, STK11, PIK3CA, TP53, PTEN, KRAS, CTNNB1, NFE2L2, NF1, and MET. ALK fusion was detected by IHC. Patients were enrolled between July 2012 and December 2013, with follow up until November 30th, 2017.Cox proportional hazards models were used to assess the ER expression on relapse free survival (RFS) and overall survival (OS). A logistic regression model was applied to assess the impact of ER (positive vs. negative) on gene alterations, using sex, smoking history, age and stage as independent variables. Results: ER expression was significantly higher in never smokers (vs. ever smokers; p = 0.022) and earlier stage (stage I vs. II-IV; p = 0.002). Patients with ER positive tumors had a longer RFS than those with negative tumors (RFS rate at 4 years: 33.7 vs. 26.5%; p = 0.021), however, there was no significant difference in OS between the two groups (p = 0.108). In the impact of ER status on the gene alterations, mutations in EGFR (p = 0.003), TP53 (p = 0.007) and CTNNB1 (p = 0.027) were significantly associated with ER expression. Multivariate analysis showed that EGFR mutations (OR = 1.394, 95%CI: 1.029-1.890, p = 0.032) and CTNNB1 mutations (OR = 0.272, 95%CI: 0.087-0.853, p = 0.026) were significantly associated with ER expression, while there was a trend for significance with TP53 mutations (OR = 0.737, 95%CI: 0.537-1.011, p = 0.059). Conclusions: ER positive status triggered the clonal EGFR mutations and suppressed the sub-clonal mutations of TP53 and CTNNB1. It is suggested that ER plays a critical role in the alterations of EGFR/TP53/ CTNNB1 axis in lung cancer evolution.


Endocrinology ◽  
1997 ◽  
Vol 138 (4) ◽  
pp. 1498-1505 ◽  
Author(s):  
Adriana Stoica ◽  
Miguel Saceda ◽  
Amina Fakhro ◽  
Harrison B. Solomon ◽  
Bradley D. Fenster ◽  
...  

2014 ◽  
Vol 2 (2) ◽  
Author(s):  
Challapalli Srikanth Reddy ◽  
Chilakala Archana ◽  
Bathalapalli SrihariRao ◽  
Shankar Reddy Dudala ◽  
Jambapuram Bharath prakash Reddy ◽  
...  

Breast carcinoma is the most common malignant tumor and the leading cause of death, in women, worldwide. It accounts for 15 % of all cancer deaths. Various protocols are in use for the assessment of prognosis, and also to assist in planningfurther management of these cases. Of various parameters, expression of Estrogen receptors (ER) is significant. The literature includes several studies showing association between the presence of estrogen receptors apart from other indicators of good prognosis like small tumor size, low histological grade, low nuclear grade and low mitotic activity. It is also a powerful predictive factor for the likelihood of benefit from adjuvant hormonal therapy including aromatase inhibitors (Anastrozole, letrozole) and Tamoxifen, an oral selective estrogen receptor modulator. All cases of Carcinoma breast presenting to S.V.R.R.G.G. Hospital, are evaluated for Estrogen Receptor status using immunochemistry, indirectly assessing the prognosis of individuals presenting to the Hospital and in turn the prognosis of the disease in the region.


2021 ◽  
Author(s):  
Chun Wai Ng ◽  
Kwong-kwok Wong

Abstract BackgroundThe prognostic value of the expression of estrogen receptor (ER) subtypes ER⍺ and ERβ in ovarian cancer has previously been evaluated by meta-analyses. However, the results are contradictory and controversial. MethodsWe conducted an updated meta-analysis with stringent inclusion criteria to ensure homogeneous studies to determine the effect of ER subtypes on ovarian cancer prognosis. Articles were retrieved by systematic search of PubMed and Web of Science for articles dated up to June 2021. Only studies with known hazard ratio (HR) and antibody clone for immunochemistry (IHC) were included. Pooled HRs with the corresponding 95% confidence intervals (CIs) were calculated for the effect of ER⍺ and ERβ expression on ovarian cancer patient progression-free survival (PFS) and overall survival (OS).ResultsA total of 17 studies were included, of which 11 and 13 studies examined the relationships between ER⍺ expression and PFS and OS, respectively, and 5 and 7 studies examined the relationships between ERβ expression and PFS and OS, respectively. Neither ER⍺ expression (random-effects model; HR=0.99, 95% CI=0.83-1.18) nor ERβ expression (fixed-effects model; HR=0.94, 95% CI=0.69-1.27) was associated with PFS. Random-effects models showed that ER⍺ expression (HR=0.81, 95% CI=0.64-1.02) and ERβ expression (HR=0.75, 95% CI=0.50-1.13) were only marginally and not significantly associated with better OS. Subgroup analysis revealed that ER⍺ expression determined using antibody clone 1D5 (HR=0.75, 95% CI=0.64-0.88) and ERβ expression determined using ERβ1-specific-antibody clone PPG5/10 or EMR02 (HR=0.65, 95% CI=0.50-0.86) were associated with significantly better OS, but ER expression determined using other antibodies was not.ConclusionsBoth ER⍺ expression and ERβ expression determined using certain antibody clones are significantly associated with OS of ovarian cancer patients, which suggests that both ER subtypes are prognostic biomarkers for ovarian cancer. The findings of this study provide new insight into the impact of ER expression on ovarian cancer prognosis.


2014 ◽  
Vol 138 (11) ◽  
pp. 1507-1513 ◽  
Author(s):  
Julie M. Jorns ◽  
Dafydd G. Thomas ◽  
Patrick N. Healy ◽  
Stephanie Daignault ◽  
Tammi L. Vickery ◽  
...  

Context Tubular carcinoma (TC) is a rare, luminal A subtype of breast carcinoma with excellent prognosis, for which adjuvant chemotherapy is usually contraindicated. Objective To examine the levels of estrogen receptor (ER) and progesterone receptor expression in cases of TC and well-differentiated invasive ductal carcinoma as compared to normal breast glands and to determine if any significant differences could be detected via molecular testing. Design We examined ER and progesterone receptor via immunohistochemistry in tubular (N = 27), mixed ductal/tubular (N = 16), and well-differentiated ductal (N = 27) carcinomas with comparison to surrounding normal breast tissue. We additionally performed molecular subtyping of 10 TCs and 10 ductal carcinomas via the PAM50 assay. Results Although ER expression was high for all groups, TC had statistically significantly lower ER staining percentage (ER%) (P = .003) and difference in ER expression between tumor and accompanying normal tissue (P = .02) than well-differentiated ductal carcinomas, with mixed ductal/tubular carcinomas falling between these 2 groups. Mean ER% was 79%, 87%, and 94%, and mean tumor-normal ER% differences were 13.6%, 25.9%, and 32.6% in tubular, mixed, and ductal carcinomas, respectively. Most tumors that had molecular subtyping were luminal A (9 of 10 tubular and 8 of 10 ductal), and no significant differences in specific gene expression between the 2 groups were identified. Conclusions Tubular carcinoma exhibited decreased intensity in ER expression, closer to that of normal breast parenchyma, likely as a consequence of a high degree of differentiation. Lower ER% expression by TC may represent a potential pitfall when performing commercially available breast carcinoma prognostic assays that rely heavily on ER-related gene expression.


1998 ◽  
Vol 5 (4) ◽  
pp. 277-285 ◽  
Author(s):  
F. Kohen ◽  
L. Abel ◽  
A. Sharp ◽  
Y. Amir-Zaltsman ◽  
D. Sömjen ◽  
...  

The expression of estrogen receptor (ER) in thymocytes was studied in young, middle-aged, and old (2, 12, and 24 months, respectively) female and male C57BL/6J mice. Western immunoblots prepared from the thymocytes of females of all age groups showed the presence of a 67-kD protein band, which has been associated with the apparent MW of denatured ER. Flow cytometry analysis o,f cells stained with a monoclonal anti-ER antibody (clone 13H2) disclosed ER expression in both females and males of all age groups.In vivotreatment with estradiol (E2) led to an increase in the specific activity of thymic creatine kinase (CK) in the female mice, whereas the male thymocytes responded with an increase in CK activity only on treatment with dihydrotestosterone (DHT). The data show no differences in ER expression between male and females, but the receptor appears not to be functional in males. Interestingly, when estradiol was applied to co-cultures of lymphoid-depleted fetal thymus (FT) explants and bone-marrow cells, or thymocytes, from young and old females, it resulted in increased cellularity of cultures containing cells of the young, and not those of the old. The proportion of CD4/CD8 phenotypes of the developing cells in these cultures was not affected by E2treatment. These observations provide a new insight into ER expression and function in T-cell development in relation to gender and age.


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