Hormones, receptors, and growth in hyperplastic enlarged lobular units: early potential precursors of breast cancer (original) (raw)
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Estrogen receptor expression in normal breast epithelium in invasive ductal carcinoma
The European Research Journal, 2020
Objectives: Invasive ductal carcinomas (IDCs) are the most important group of malignant breast tumors and constitute 75-80% of breast carcinomas. While IDCs often present with ductal carcinoma in situ (DCIS), they sometimes include a low level of DCIS or they do not include any accompanying DCIS at all. We planned this study to compare estrogen receptor (ER) expression levels in normal mammary epithelium in IDCs with extensive DCIS (Group I) and IDCs without DCIS (Group II). Methods: Eighty IDC cases selected from among samples that were analyzed in our pathology laboratory. The cases were assessed retrospectively in light of immunohistochemical analysis results and pathology reports. Evaluation of immunohistochemistry: ER positivity in IDC was defined with a nuclear staining of more than 10% of cancer cells regardless of intensity of staining. Presence of cells showing nuclear staining for normal breast epithelium was classified in 4 groups according to their quantity and intensity. These were: 0-None: No staining was observed, 1-Single: One or two positive cells, 2-Dispersed: Dispersed positive cells surrounded by negative cells, 3-Adjoined: 10 or more positive cells contacting each other. Results: Statistically no significant difference was found between Group I and Group II in terms of ER expression. Group I were more prevalent in younger and in the premenopausal period than Group II. Conclusions: According to our study, there was no difference between Group I and Group II in terms of ER expression. But the significantly presence Group I in more young people and in premenopausal women suggests that these carcinomas develop due to high estrogen levels and that Group II develop independently than estrogen. This suggests that these groups may have different carcinogenesis and etiologies. We therefore think that this first study on IDCs with extensive DCIS and IDCs without DCIS should be supported by new research studies.
The American Journal of Surgical Pathology, 2005
Aim: To compare the expression of estrogen receptor α (ERα), Bcl-2 and NF-κB P65 in endometrial polyps from patients with and without endometriosis. Methods: Immunohistochemistry was used to characterize the expression of ERα, Bcl-2 and NF-κB P65 in proliferative phase endometrial polyps from patients with and without endometriosis. H-Scores indicating the staining intensity for ERα, Bcl-2 and NF-κB P65 in the glandular epithelium and stroma were measured separately. Apoptotic cells were detected with the use of the dUTP nick-end labeling (TUNEL) assay. Results: Bcl-2 was expressed in the cytoplasm of glandular epithelial cells, whereas ERα was expressed in the nuclei of both glandular epithelial and stromal cells. NF-κB P65 was observed in the cytoplasm of both glandular epithelial and stromal cells. The H-scores for Bcl-2 in the endometrial glands significantly higher in the endometriosis polyp group than in the non-endometriosis polyp group. The H-scores for ERα in both stromal and glandular epithelial cells were significantly higher in the endometriosis polyp group than in the non-endometriosis polyp group. The H-scores for Bcl-2 and ERα were positively correlated in all of the women examined. Apoptotic cells in the endometriosis polyp group were significantly less than that of the non-endometriosis polyp group. Conclusion: There expression levels of Bcl-2 and ERα, both of which were significantly increased in the polyps of endometriosis patients compared to those of patients without endometriosis, were positively correlated. These results suggested that imbalanced apoptosis secondary to abnormally high ERα expression was responsible for the high prevalence of polyps in endometriosis patients.
Journal of Personalized Medicine
Normal breast tissue undergoes great variations during a woman’s life as a consequence of the different hormonal stimulation. The purpose of the present study was to examine the hormonal receptor expression variations according to age, menstrual cycle, menopausal state and body mass index. To this purpose, 49 tissue samples of normal breast tissue, obtained during surgery performed for benign and malignant conditions, were immunostained with Estrogen (ER), Progesterone (PR) and Androgen receptors (AR). In addition, Ki67 and Gross Cystic Disease Fluid Protein were studied. The data obtained revealed a great variability of hormone receptor expression. ER and AR generally increased in older and post-menopausal women, while young women presented a higher proliferative rate, evaluated with Ki67. PR increase was observed in women with BMI higher than 25. The different hormonal receptor expression could favor the development of breast cancer.
Immunohistochemical expression of estrogen receptors alpha and beta in lobular neoplasia
Virchows Archiv, 2007
To date, two isoforms of estrogen receptors (ER) have been identified, cloned, and characterized from several species, estrogen receptor-␣ (ER␣) and estrogen receptor- (ER). Although the presence of ER␣ has been demonstrated in normal and tumoral canine mammary tissues, the issue of ER expression has not been addressed in the dog. In this study, we have analyzed the expression of ER in formalin-fixed, paraffinembedded tissue samples of nonaltered mammary gland, 30 malignant (six complex carcinoma, 12 simple carcinoma, three carcinosarcoma, and nine carcinoma or sarcoma in benign tumor), and five benign (one fibroadenoma, one complex papilloma, one complex adenoma, and two benign mixed tumors) mammary tumors of the dog by using a polyclonal ER antibody and the avidin-biotin-peroxidase complex immunohistochemical technique. Our results show that high numbers of normal ductal and acinar epithelium and approximately one third of canine mammary tumors express ER. This expression was higher in benign than in malignant tumors. Furthermore, expression was higher in complex and mixed histologic subtypes of malignant tumors when compared with simple subtypes.
Folia Histochemica et Cytobiologica, 2009
Contents of estrogen receptors (ER) and progesterone receptors (PgR) in cells of breast cancers represent strong predictive factors. The higher is the contents of ER and PgR in breast cancer, the higher is a probability of obtaining a response to hormonal therapy and prognosis for the patient is better. In a routine manner, all tumours of mammary gland are subjected to evaluation of ER and PgR expression using immunohistochemistry. Forty ductal breast cancers (pT 2 N 0 ) were subjected to an immunohistochemical evaluation (IHC) aimed at detection of ER and PgR expression. From every tumour three samples were taken for immunohistochemical studies: the lateral one from the side of axilla (ER-1; PgR-1); the median one (ER-2; PgR-2) and the medial one from the side of sternum (ER-3; PgR-3). The levels of both ER and PgR expression proved to be highly differentiated between the medial zone of the tumour and its periphery. The distinct expression of ER and PgR in ductal breast cancers, dependent on evaluated zone of the tumour, confirms its heterogenous character and exerts an effect on the type of applied treatment.
Estrogen responsiveness and control of normal human breast proliferation
Journal of mammary gland biology and neoplasia, 1998
Our understanding of the hormonal control of the proliferation of normal human breast epithelium is still surprisingly meager. However, the results of a number of recent studies have confirmed that estrogen is the major steroid mitogen for the luminal epithelial cell population (the usual targets for neoplastic transformation). Estrogen seemingly exerts its effects on cell division indirectly as there is complete dissociation between the population of luminal epithelial cells expressing the estrogen receptor (ER)4 and those that proliferate. We suggest that the ER-negative proliferating cells represent a precursor or stem cell population that differentiates to ER-containing, nonproliferative cells. In turn, these ER-positive cells act as 'estrogen sensors' and transmit positive or negative paracrine growth signals to the precursor cells depending on the prevailing hormonal environment. As yet there is no direct evidence supporting this hypothesis but we suggest ways in which...
Estrogen receptor ? expression in normal human breast epithelium is consistent over time
International Journal of Cancer, 2002
If increased expression of estrogen receptor ␣ (ER) in benign breast epithelium increases susceptibility to breast cancer, such overexpression should be stable over time. There are no published data regarding this important aspect of ER expression in breast epithelium. We examined the temporal consistency of ER expression in the normal breast tissue of 28 women who had 2 separate breast surgical procedures, at least 6 months apart (mean interval, 2.8 years). Paraffin embedded breast tissue blocks containing an adequate sample of normal breast epithelium and no cancer, were sectioned and processed using the 6F11 antibody and standard immunohistochemical techniques. The ER labelling index (ER LI) was calculated by counting a mean of 2,000 epithelial cells. The median ER LI at first sampling was 13.6 and at second sample 15.5, with R 2 ؍ 0.34 and p ؍ 0.001. The ER LI was categorized into high and low values, using a threshold of 10. Twenty-four women (85.7%) showed concordance of high and low expression between the 2 samples (p ؍ 0.002). There were 11 women who were premenopausal at both time points. Among them, much of the variation in ER LI was explained by differences in the menstrual cycle day at the time of sampling and adding the day of cycle to the regression model substantially improved the correlation between first and second labeling indices. These data suggest that ER expression of normal breast tissue is fairly consistent over time and support the notion that overexpression of ER in normal epithelium is a constant feature of the high risk breast.
Acta clinica Croatica, 2010
Invasive lobular carcinoma is a distinct biological entity with several histologic variants the prognostic value of which is not fully elucidated. The aim of this study was to determine the immunohistochemical expression of estrogen receptors (ER) and progedterone receptors (PR) in subtypes of lobular breast carcinoma (classic and variant types) and to correlate them with clinical and tumor parameters. Fifty lobular carcinomas, i.e. 33 classic and 17 variant, were analyzed. The classic type was more common (66%) and found in older women (61 years of age), smaller in size (1.5 cm), with N0 status and modestly positive ER and PR. The variant types were more frequent in younger women (55 years of age), larger in size (2.5 cm), with N1 status and maximal positive ER and PR. ER was expressed in 82% and PR in 78% of all tumors, mostly with maximal expression. Only one tumor of the classic type was HER/2neu 3+, ER and PR-. ER expression was significantly associated with a decreased inciden...
International Journal of Cancer, 2009
Estrogens play a central role in the etiology of breast cancer, and results from observational studies and randomized trials have also implicated progestins. The effects of these hormones in the mammary tissue are exerted through binding with specific receptor proteins in the cell nucleus. It has been proposed that higher estrogen receptor alpha expression in the normal breast epithelium may increase breast cancer risk. In a study in Greece, we determined estrogen alpha and progesterone receptor expression in normal mammary tissue adjacent to the pathological tissue from 267 women with breast cancer and 299 women with benign breast disease. Mouse monoclonal antibodies specific for estrogen receptor alpha and progesterone receptor were applied. The H-index, which incorporates frequency and intensity of staining of the cells, and can range from 0 to 300, was deemed positive when it exceeded 9. Among premenopausal women, there was no evidence for an association with breast cancer risk for expression of either type of receptors. Among postmenopausal women, breast cancer risk was inversely associated with expression of both estrogen alpha (odds ratio (OR) 5 0.39; p 5 0.015) and progesterone (OR 5 0.40; p 5 0.
Carcinoma of the breast is the most common malignancy of women globally and the incidence has more risen in recent years. The current study was conducted with the objective of assessing estrogen receptor (ER) and progesterone receptor (PR) reactivity patterns of mammary cancers and to evaluate their association with clinicopathological features. A total of 61 cases of breast carcinoma were examined retrospectively using immunostains for estrogen receptor (ER) and progesterone receptor (PR). Staining pattern and intensity were correlated with histological subtypes and nuclear grades of tumors. The left breast was more commonly involved (57%) and tumor size ranged from 0.5-13.0cm. The predominant morphology was infiltrating ductal carcinoma (85.3%). The majority of the cases presented as grade II (55.3%) lesions with tumor necrosis (70%) and lymph node involvement (71.3%). Positive nuclear staining for ER and PR was observed in 70.5% and 57.5 % of invasive carcinomas, respectively. In ER+ cases, fifty five cases (90%) gave diffuse immunohistochemical reaction for ER; inthe remaining 10%, a focal ER reaction was seen. In PR+ cases, 49 cases (80%) gave diffuse immunohistochemical reaction for PR and Inremaining 20% of PR+ tumors, the reaction was heterogeneous. In ductal infiltrative carcinomas the percentage of cases showed ER+ nuclear labeling is higher than those in cases of infiltrative lobular carcinomas. Assessment of ER and PR as prognostic markers for the clinical management of breast cancer patients is strongly advocated to provide best therapeutic options.