scholarly journals Estrogen Receptor Expression Is High but Is of Lower Intensity in Tubular Carcinoma Than in Well-Differentiated Invasive Ductal Carcinoma

2014 ◽  
Vol 138 (11) ◽  
pp. 1507-1513 ◽  
Author(s):  
Julie M. Jorns ◽  
Dafydd G. Thomas ◽  
Patrick N. Healy ◽  
Stephanie Daignault ◽  
Tammi L. Vickery ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Ductal Carcinoma ◽  
Normal Breast ◽  
Receptor Expression ◽  
Luminal A ◽  
Tubular Carcinoma ◽  
Ductal Carcinomas ◽  
Well Differentiated ◽  
Er Expression

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.

G-protein Coupled Estrogen Receptor Expression in Growth Hormone Secreting and Non-Functioning Adenomas

2020 ◽  
Author(s):  
Hande Mefkure Ozkaya ◽  
Muge Sayitoglu ◽  
Nil Comunoglu ◽  
Eda Sun ◽  
Fatma Ela Keskin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Protein Expression ◽  
G Protein ◽  
Estrogen Receptor Α ◽  
Receptor Expression ◽  
Positive Correlation ◽  
Polymerase Chain ◽  
G Protein Coupled ◽  
Transforming Gene

Abstract Purpose To evaluate the expression of G-protein coupled estrogen receptor (GPER1), aromatase, estrogen receptor α (ERα), estrogen receptor β (ERβ), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) in GH-secreting and non-functioning adenomas (NFA). Methods Thirty patients with acromegaly and 27 patients with NFA were included. Gene expression was determined via quantitative reverse transcription polymerase chain reaction (QRT-PCR). Protein expression was determined via immunohistochemistry. Results There was no difference, in terms of gene expression of aromatase, ERα, PTTG, and FGF2 between the two groups (p>0.05 for all). ERβ gene expression was higher and GPER1 gene expression was lower in GH-secreting adenomas than NFAs (p<0.05 for all). Aromatase and ERβ protein expression was higher in GH-secreting adenomas than NFAs (p=0.01). None of the tumors expressed ERα. GPER1 expression was detected in 62.2% of the GH-secreting adenomas and 45% of NFAs. There was no difference in terms of GPER1, PTTG, FGF2 H scores between the two groups (p>0.05 for all). GPER1 gene expression was positively correlated to ERα, ERβ, PTTG, and FGF2 gene expression (p<0.05 for all). There was a positive correlation between aromatase and GPER1 protein expression (r=0.31; p=0.04). Conclusions GPER1 is expressed at both gene and protein level in a substantial portion of GH-secreting adenomas and NFAs. The finding of a positive correlation between GPER1 and ERα, ERβ, PTTG, and FGF2 gene expression and aromatase and GPER1 protein expression suggests GPER1 along with aromatase and classical ERs might mediate the effects of estrogen through upregulation of PTTG and FGF2.

Tubular Carcinoma of the Breast: Further Evidence to Support Its Excellent Prognosis

2010 ◽  
Vol 28 (1) ◽  
pp. 99-104 ◽  
Author(s):  
Emad A. Rakha ◽  
Andrew H.S. Lee ◽  
Andrew J. Evans ◽  
Sindhu Menon ◽  
Nancy Y. Assad ◽  
...  
Keyword(s):  
Ductal Carcinoma ◽  
Disease Free Survival ◽  
Distinct Type ◽  
Second Primary ◽  
Low Grade ◽  
Breast Cancers ◽  
Luminal A ◽  
Cancer Specific Survival ◽  
Tubular Carcinoma ◽  
Molecular Features

Purpose Although tubular carcinoma (TC) is known to have a favorable prognosis, it is still unknown whether this subtype represents a distinct type of breast carcinoma or whether it behaves like other low-grade luminal A–type breast carcinomas. Methods In this study, we performed a retrospective analysis of a large well-characterized series of breast cancers (2,608 carcinomas) to assess the clinicopathologic and molecular features and prognostic value of TC compared with grade 1 ductal carcinomas of the breast. Results When compared with grade 1 ductal carcinoma (n = 212), TC (n = 102) was more likely to be detected on mammographic screening, had smaller median size, and less frequently showed lymphovascular invasion. Compared with grade 1 ductal carcinoma, TC was associated with longer disease-free survival (χ2 = 13.25, P < .001) and breast cancer–specific survival (χ2 = 8.8, P = .003). In this study, none of the patients with TC developed distant metastasis or died from the disease without an intervening recurrence as invasive carcinoma of different histologic type. Conclusion We conclude that the biologic behavior of TC is excellent and is more favorable than that of grade 1 ductal carcinoma. Patients with TC may be at risk of developing second primary carcinomas in the contralateral breast, which may be of higher grade and poorer potential prognostic outcome. In addition, patients with TC seem to have a close to normal life expectancy, and as a consequence, adjuvant systemic therapy may not be justified in their routine management.

scholarly journals The clinical utility of circulating neuroendocrine gene transcript analysis in well-differentiated paragangliomas and pheochromocytomas

2017 ◽  
Vol 176 (2) ◽  
pp. 143-157 ◽  
Author(s):  
M Pęczkowska ◽  
J Cwikla ◽  
M Kidd ◽  
A Lewczuk ◽  
A Kolasinska-Ćwikła ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multivariate Analysis ◽  
Clinical Utility ◽  
Progressive Disease ◽  
Somatostatin Receptor ◽  
Blood Analysis ◽  
Receptor Expression ◽  
Gene Transcript ◽  
Transcript Analysis ◽  
Well Differentiated

Context Paragangliomas and pheochromocytomas (PPGLs) exhibit variable malignancy, which is difficult to determine by histopathology, amine measurements or tissue genetic analyses. Objective To evaluate whether a 51-neuroendocrine gene blood analysis has clinical utility as a diagnostic and prognostic marker. Design Prospective cohort study. Well-differentiated PPGLs (n = 32), metastatic (n = 4); SDHx mutation (n = 25); 12 biochemically active, Lanreotide treated (n = 4). Nine patients had multiple sampling. Age- and gender-matched controls and GEP-NETs (comparators). Methods Circulating neuroendocrine tumor mRNA measured (qPCR) with multianalyte algorithmic analysis. Metabolic, epigenomic and proliferative genes as well as somatostatin receptor expression were assessed (averaged, normalized gene expression: mean ± s.e.m.). Amines were measured by HPLC and chromogranin A by ELISA. Analyses (2-tailed): Fisher’s test, non-parametric (Mann–Whitney), receiver-operator curve (ROC) and multivariate analysis (MVA). All data are presented as mean ± s.e.m. Results PPGL were NETest positive (100%). All exhibited higher scores than controls (55 ± 5% vs 8 ± 1%, P = 0.0001), similar to GEP-NETs (47 ± 5%). ROC analysis area under curve was 0.98 for differentiating PPGLs/controls (cut-off for normal: 26.7%). Mutation status was not directly linked to NETest. Genetic and molecular clustering was associated (P < 0.04) with NETest scores. Metastatic (80 ± 9%) and multicentric (64 ± 9%) disease had significantly (P < 0.04) higher scores than localized disease (43 ± 7%). Progressive disease (PD) had the highest scores (86 ± 2%) vs stable (SD, 41 ± 2%) (P < 0.0001). The area under the curve for PD from SD was 0.93 (cut-off for PD: 53%). Proliferation, epigenetic and somatostatin receptor gene expression was elevated (P < 0.03) in PD. Metabolic gene expression was decreased in SDHx mutations. Repeat NETest measurements defined clinical status in the 9 patients (6 SD and 3 PD). Amine measurement was non-informative. Multivariate analysis identified NETest >53% as an independent prognostic factor. Conclusion Circulating NET transcript analysis is positive (100% diagnostic) in well-differentiated PCC/PGL, scores were elevated in progressive disease irrespective of mutation or biochemical activity and elevated levels were prognostic.

scholarly journals Impact of estrogen receptor expression and other clinicopathologic features on tamoxifen use in ductal carcinoma in situ

Cancer ◽  
2006 ◽  
Vol 106 (10) ◽  
pp. 2113-2118 ◽  
Author(s):  
R. Barry Hird ◽  
Alfred Chang ◽  
Vincent Cimmino ◽  
Kathleen Diehl ◽  
Michael Sabel ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Receptor Expression ◽  
Estrogen Receptor Expression ◽  
Clinicopathologic Features

Classification of subtype using IHC patterns for treatment decision of DCIS.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12035-e12035
Author(s):  
Yuko Date ◽  
Masafumi Takimoto ◽  
Toshio Morohoshi ◽  
Seigo Nakamura
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Prognostic Index ◽  
Receptor Expression ◽  
Luminal A ◽  
Ki 67 ◽  
Risk Of Recurrence

e12035 Background: Ductal carcinoma in situ (DCIS) is a heterogenous group of breast lesion and demands a broad range of surgical management techniques. Previous studies reported the importance of receptor expression and referred to the risk of recurrence.We classified ductal carcinoma in situ (DCIS) into 4 subtypes using IHC staining (ER, PgR, HER2 and Ki-67) and investigated the frequency and their characteristics. Also we investigated whether this classification is related to the risk of recurrence. Methods: 117 women who underwent operation between 2010 and 2012 were included our study. We defined 4 subtypes as follows; luminal A (LA), ER and/or PgR (HR)(+) HER2(-) Ki-67(low), luminal B (LB), HR(+) HER2(-) Ki-67(high) or HR(+) HER2(+),HER2(H), HR(-) HER2(+), and basal-like(BL), HR(-) HER2(-).We also evaluated the risk of recurrence using Van Nuys Prognostic Index (VNPI), an algorithm based on DCIS size, nuclear grade (NG), necrosis, margin width and patient age. Results: The frequency of subtype was as follows; LA 77 cases (65.8%), LB 18 (15.3%), H 14 (12.0%) and BL 8 (6.8%). LA tended to smaller size (average: 3.2cm, range: 0.2-12), low NG (NG1 was 97.4%). In a contrary, H and BL were larger size (average: 3.7cm (H), 4.5cm (BL)) and high NG (these percentages of NG3 were 64.3% (H) and 50.0% (BL)). All of the BL had necrosis. About half of the LA was VNPI 6 and 7, but many of the other subtypes were more than VNPI 7 (p=0.02). Conclusions: Classification of subtypes using IHC patterns is simple, useful and, moreover, that are related to the risk of recurrence. Though it is important whether the woman is BRCA1/2 mutation carrier, we might be determined a treatment of DCIS by the subtype.

Impact of Estrogen Receptor Expression on Prognosis of Ovarian Cancer According to Antibody Clone Used for Immunohistochemistry: A Meta-analysis

2021 ◽  
Author(s):  
Chun Wai Ng ◽  
Kwong-kwok Wong
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Random Effects ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Receptor Expression ◽  
Cancer Prognosis ◽  
Ovarian Cancer Prognosis ◽  
The Impact ◽  
Er Expression

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.

The Relationship Between p63 and p53 Expression in Normal and Neoplastic Breast Tissue

2003 ◽  
Vol 127 (3) ◽  
pp. 336-340 ◽  
Author(s):  
Alfredo Ribeiro-Silva ◽  
Leandra N. Zambelli Ramalho ◽  
Sérgio Britto Garcia ◽  
Sérgio Zucoloto
Keyword(s):  
Estrogen Receptor ◽  
Breast Tissue ◽  
Smooth Muscle Actin ◽  
Myoepithelial Cells ◽  
Normal Breast ◽  
Cytokeratin 7 ◽  
Breast Carcinomas ◽  
P53 Expression ◽  
Divergent Differentiation ◽  
Ductal Carcinomas

Abstract Context.—p63 is a recently described p53 homologue. Despite structural homology, they have different activities. Objectives.—To obtain new insights into the role of p63 in normal and neoplastic breast tissue and to verify the possible association between p63 and p53 in breast carcinomas. Design.—Immunohistochemistry in 85 breast carcinomas using p63, smooth muscle actin (1A4), p53, estrogen receptor, and progesterone receptor. The p63-positive cases were submitted to a double-immunolabeling study using p63 with 1A4, cytokeratin 7, and 34βE12. Clinical data were retrieved from medical files. Results.—p63, like 1A4, stained a single and continuous layer surrounding normal breast ductal and alveolar epithelium. In carcinomas, p53 was expressed in 21.17% of carcinomas, whereas p63 was expressed only in poorly differentiated ductal carcinomas (11.76% of cases). p63-positive cells coexpressed 1A4 and 34βE12, but not cytokeratin 7. Expression of p63 correlated with pathologic staging, tumor size, histologic grading, nodal metastasis, and estrogen receptor negativity. Conclusions.—p63 is a specific myoepithelial cell marker in normal breast tissue and is expressed in a minority of breast carcinomas, being seen only in grade III ductal carcinomas. In ductal carcinomas, malignant p63-positive cells have an immunophenotype similar to that of myoepithelial cells, suggesting that these cells originate from a primary progenitor cell that underwent divergent differentiation to ductal and myoepithelial cells during clonal expansion. Our study argues against a direct role in mammary tumorigenesis. However, p53 is rarely coexpressed with p63, suggesting that p63 could act indirectly as an oncogene by inhibiting p53. This hypothesis could also explain why p63 correlated with several other indicators of poor prognosis.

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