Steroid hormone receptors in benign breast diseases

Benign breast diseases generally occur in women with progesterone insufficiency and an unopposed estrogen status. This hormonal imbalance is also a main risk factor for breast cancer in the long run. The presence of estradiol and progesterone receptors in benign breast disease are additional proof of their hormone dependence. The level of receptors is higher when the epithelial cellularity is high and also in more recent lesions, and younger women. The level and subcellular location of the receptors also depend on the endogenous secretion of steroids: their level varies throughout the menstrual cycle, and it is maximal at the end of the follicular phase, due to the high estradiol secretion. The cytosol and nuclear level and location of the receptors are also modified by hormonal therapy: estrogen-progestagens given as a contraceptive, or progestins given as a substitutive and antiestrogen therapy. These modifications constitute a biochemical basis for the hormonal progestagen treatment of benign breast diseases.     

Anatomopathology of breast cancer and hormone receptors

The authors present the results obtained from a series of 511 operable adenocarcinomas (were excluded sarcoma, non infiltrating carcinoma and tumours too small for dosage). Estrogen (ER) and progesterone (PR) receptors were determined on the cytosol with a single saturating-dose method (5nM). The cut-off between positive and negative tumours was 100 fm/g tissue with a border area (100-200 fm/g). Correlation between ER, PR and the followed histological characters were studied: 1) Anatomic size of the tumour: no correlation was found. 2) Histological type: there was a significant correlation (p less than 0.001) between ER, PR and current histological types: among the infiltrating ductal carcinoma, the highly differentiated ones were more often ER+, PR+ (69%) than the atypical one (33%). This correlation remained according to the hormonal status of the patients. The particular types but infiltrating lobular carcinoma were mainly without receptors. 3) Histological grading: there was a significant correlation (p less than 0.001) between this character and the (ER, PR) rate of the tumour: 25% of the tumours of grade III were (ER+, PR+) against 57% of the grade I. As for the histological type, this correlation remained according to the hormonal status of the patients. 4) Stromal reaction: there was a significant correlation between (ER, PR) and inflammatory reaction (p = 0.002) or elastosis (p = 0.002) respectively. Inflammatory reaction was more often reported in tumours without receptors (73% in ER-, PR- tumours against 56% in ER+, PR+ ones). On the opposite, elastosis was correlated with the presence of receptors (52% in ER+, PR+ tumours against 34% in ER-, PR- ones). 5) Lymph-nodes involvement: no correlation was found with hormonal receptors (47% ER+, PR+ in the N- cases against 48% in the N+ cases).     

Steroid hormone receptors in human salivary gland tumours.

Major salivary gland tumours were studied for the presence of hormone receptors for oestrogen and progesterone. Of the eight salivary gland tumours exhibiting varied histology, none showed high affinity receptors for oestrogen or progesterone. Salivary tissue from four patients with non-neoplastic salivary gland disease was also studied and found not to contain high affinity receptor sites. The absence of hormone receptors in these glands suggests that such tumours are not dependent on endocrine function.     

Methods of detection and quantification of hormone receptors in breast cancer

This article reviews the problems inherent to the detection and assay of steroid hormone receptors in human target tissues and in pathological tissues. The biochemical characteristics of the hormone-receptor interaction are described, i.e., high affinity, strict specificity and limited number of binding sites. The calculation of these parameters is given. This is followed by an analysis of the practical problems involved in biochemical assays: (a) receptor protein stabilization, choice and concentration of radioligand, determination of incubation conditions (time and temperature) for the measurement of the number of binding sites in an exchange assay; (b) the various methods of separating bound from free steroid are discussed and their respective advantages and disadvantages as routine methods as opposed to research techniques are probed. The case of receptor determinations in human pathological tissues is analysed next with special emphasis on sample preparation, stabilization, storage and transport and also on plasma contamination and tissue heterogeneity. The various methods that can be used to detect steroid binding sites in pathological tissues are described: (i) biochemical techniques, (ii) autoradiography, (iii) histochemistry, in order to highlight their respective merits for the selection of hormone-sensitive pathological tissues.     

激素受体相关的微小RNA和乳腺癌

一、微小RNA(miRNA)在乳腺癌中的表达和调控 乳腺癌是一种激素依赖性肿瘤,雌激素受体(ER)和孕激素受体(PR)已作为预测内分泌治疗疗效的关键指标.近年来的一些研究显示,乳腺癌的发生、浸润、转移和耐药与一些miRNA关系密切,miRNA通过调节mRNA的翻译在转录后水平对基因的表达进行调控.研究还显示,雄激素受体(AR)的转录活化可调节miRNA的表达,与乳腺癌的进展和预后有着重要的潜在相关性[1].     

The value of imprint cytology in cytochemical detection of steroid hormone receptors in breast cancer

Steroid hormone receptors were studied in 42 patients with primary, recurrent or metastatic breast cancer in cryostat frozen section and imprint preparations. The ligands, 17 B-estradiol-6-carboxymethyloxine-bovine serum album fluorescein isothiocyanate (FITC-BSA estradiol) and hydroxyprogesterone-hemisuccinate bovine serum album tetramethylrhodamine isothiocyanate (TMRITC-BSA progesterone) were used in the fluorescent cytochemical method. Results were compared with standard dextran-coated charcoal (DCC) biochemical assay. Overall, significant correlation between biochemical values and cytochemical fluorescence results was found. However, the imprint results were more sensitive and more specific than the frozen section results. A statistically significant difference (P less than 0.05) was observed between touch preparation material and frozen section specimens by the fluorescent method.     

Oestrogen receptors in human breast cancer

Summary Histopathological factors which might explain inconsistency in published data attempting to correlate oestrogen receptor content (ER) and pathological features in primary breast tumours have been investigated in 194 cases. It was found, that unequal assessment of tumour type and of histological grading between observers is one important factor. In terms of grading, however, heterogeneity of growth pattern within the same tumour seems to be of greater significance. No significant correlation was found between histological type of tumour and ER content. However, a trend towards a correlation between the extent of tubule formation (as an indication of differentiation) and ER content was observed.Sponsored by The Danish Cancer Society     

Steroid hormone receptors in endometrial stromal sarcomas. A biochemical and immunohistochemical study.

Seven cases of endometrial stromal sarcoma (five low grade and two high grade) were analyzed immunohistochemically for the presence of estrogen and progesterone receptors. In four cases (three low grade and one high grade), these results were compared to biochemical findings. All low-grade endometrial stromal sarcomas were positive for progesterone receptors using immunohistochemical techniques. These results correlated well with biochemical evaluation of progesterone receptors. The high-grade endometrial stromal sarcomas were negative for progesterone and estrogen receptors by both methods. The advantages of immunohistochemical evaluation of steroid receptors have been well established in breast and endometrial carcinomas. This study demonstrates the usefulness of this technique in endometrial stromal sarcomas.     

The immunohistochemical detection of steroid hormone receptors in breast cancer: open problems and new perspectives

Steroid hormone receptor analysis is a major determinant for adjuvant therapy and prognosis in breast cancer. The immunohistochemical analysis of oestrogen and progesterone receptors is a widely used method that is gradually replacing the traditional and clinically validated dextran charcoal radioactive ligand binding assay. However, the immunohistochemical method needs careful attention to ensure adequate quality assurance. The critical points to be considered include: (a) fixation of specimens; (b) antigen retrieval procedures; (c) type of antibodies used; (d) quantification of the staining; and (e) internal and external controls. The introduction of new reagents that can identify previously unrecognised isoforms of the oestrogen (beta isoform) and progesterone (isoform B) receptors may be of interest in the evaluation of prognosis and response to therapy.     

Cytology and hormonal receptors in breast cancer

Even in advanced tumors of the breast, it may be interesting to know the steroid receptor status (RS) for therapeutic and prognostic purposes. When, for clinical reasons, surgical biopsy is not advisable, a morphologic technique may be attempted on cytological material. In the past few years, we have employed the cytochemical method described by Lee (RSf) on cytological material obtained from 31 primary and 34 secondary tumors; adequate material and follow-up were available in 42 cases. Patients with positive results (strong and diffuse fluorescence of neoplastic cells) usually had better prognosis and longer disease-free interval and total duration of disease. The majority of patients responded to endocrine manipulation. In contrast, weak positivity or negative results were associated with a poorer prognosis. If these results are confirmed in larger series of cases and for longer periods of observation, the morphological evaluation of RS on cytological material could significantly contribute to the management of breast cancer patients.     

Steroid receptors in benign mastectomy tissue

Estrogen and progesterone receptors (ERs and PRs, respectively) were measured in both cancerous and noncancerous components of 104 modified radical mastectomy specimens. In addition, ER and PR levels were determined for 14 benign breast specimens obtained by reduction mammoplasty. The receptor levels were measured by scatchard method. Each of these groups--cancerous, corresponding noncancerous, and mammoplasty specimens--were divided into subgroups according to their receptor levels. Fourteen of the 104 noncancerous specimens were found to be ER positive (ER+). Most cases of ER+ noncancerous tissue (13 of 14 cases) were associated with ER+ tumors. The reverse was not true because only 13 of 64 cases of the ER+ tumors were associated with positive ER in their noncancerous counterparts. Comparable results were obtained for PR. The average ER-PR level of the noncancerous mastectomy tissue was significantly higher than that of the mammoplasty specimens despite the similar histologic findings in both groups.     

Effect of autologous serum and steroid hormone receptors on direct cloning of human breast cancer

Thirty-seven samples of human primary breast cancer were processed for direct cloning in methylcellulose (MC) cultures. Of the 37 specimens plated, 19 tumors (51%) grew with a plating efficiency (PE) of 0.012%. Both growing and nongrowing tumors belonged mostly to the ductal histologic type. The use of autologous serum v fetal calf serum did not affect the PE. Moreover, a negative correlation was found between the level of estrogen receptors and especially of progesterone receptors (PRs) and the ability of tumors to grow in MC culture. These findings underline the difficulty of cloning fresh specimens of human solid tumors and indicate that malignant cells with a high concentration of PRs may also have a degree of differentiation that leads to a reduced clonogenic ability.     

Quantum dots-based molecular classification of breast cancer by quantitative spectroanalysis of hormone receptors and HER2

The emerging molecular breast cancer (BC) classification based on key molecules, including hormone receptors (HRs), and human epidermal growth factor receptor 2 (HER2) has been playing an important part of clinical practice guideline. The current molecular classification mainly based on their fingerprints, however, could not provide enough essential information for treatment decision making. The molecular information on both patterns and quantities could be more helpful to heterogeneities understanding for BC personalized medicine. Here we conduct quantitative determination of HRs and HER2 by quantum dots (QDs)-based quantitative spectral analysis, which had excellent consistence with traditional method. Moreover, we establish a new molecular classification system of BC by integrating the quantitative information of HER2 and HRs, which could better reveal BC heterogeneity and identify 5 molecular subtypes with different 5-year prognosis. Furthermore, the emerging 5 molecular subtypes based on simple quantitative molecules information could be as informative as multi-genes analysis in routine practice, and might help formulate a more personalized comprehensive therapy strategy and prognosis prediction.