Occurrence, regulation, and significance of progesterone receptors in human meningioma

The abundant expression of progesterone receptors (PR) in human meningiomas is well established. It is unknown, however, how PR expression is regulated, especially since estrogen receptors (ER) are virtually absent in these tumors. At the mRNA level, ER splice variants occur in meningioma but these appear not to be involved in the apparently autonomous PR expression. In an earlier study, because other ER-inducible proteins were either not expressed at all (pS2) or were expressed at a very low level compared to their expression in breast cancer (Cathepsin-D), the authors have postulated that the autonomous PR expression in meningioma is PR promoter-related rather than ER-related and have studied PR expression in cultured meningioma cells. PR levels appeared to decrease rapidly in vitro in monolayer as well as in three dimensional spheroid cultures. Culture conditions thus are not yet sufficient for the quantitative evaluation of PR expression. To evaluate whether PR deterioration is associated with cell turnover (meningiomas grow much faster in vitro than in vivo), the relationship between expression of the apoptotic proteins Bcl-2 and Bax and PR expression was investigated. Bcl-2 expression was found to be highest in meningioma with low PR levels, and in breast cancer tissue with high PR levels. Bax expression was not related to PR expression in any of the two tissues. Given the potential benefit of antiprogestin treatment and the occurrence in meningiomas of a protein capable of binding to the estrogen-responsive element, the expression of PR in meningioma remains a fascinating phenomenon which requires further investigation.     

Allelic genes involved in artery compliance and susceptibility to sporadic abdominal aortic aneurysm

Vascular smooth muscle cells (VSMCs) synthesize elastin (ELN), major protein of aortic tunica media which confers strength and elasticity to aortic wall. Protein loss or distortion is typical in aneurysm tunica media. Transforming growth factor β1 (TGFβ1) inhibits growth and connective protein expression of abdominal VSMCs cultures. Also, in atherogenic studies, estrogen (but not estrogen plus progestin) treatments inhibit aortic collagen accumulation and elastic loss, risk factors to subsequent aortic enlargement. Therefore, polymorphisms of ELN, estrogen receptor (ER) and β (ERβ), progesterone receptor (PR) and TGFβ1 genes and their products may be involved in the abdominal aortic aneurysm (AAA) development. Using PCR-RFLP method, we analyzed ELN RmaI (exon 16), ER PvuII-XbaI (intron 1), ERβ AluI (exon 8), PR TaqI (intron 7) and TGFβ1 Bsu36I (−509 bp, promoter) polymorphisms in 324 Caucasian male subjects: 225 healthy controls (mean age 71.20 ± 6.85 years) and 99 unrelated AAA patients (mean age 69.8 ± 7.1 years). No difference in ELN, ER, PR and TGFβ1 allele frequencies was observed in AAA patients versus controls (P > 0.05). However, because possessing at least an ERβ AluI restriction site was statistically associated to AAA onset (χ² = 5.220; OR = 1.82, P < 0.05), ERβ polymorphism was proposed as genetic determinant in the AAA susceptibility.     

Estrogen receptor variants and mutations

There is a large and increasing body of experimental and clinical data supporting the existence of variant estrogen receptor (ER) proteins in both normal and neoplastic estrogen target tissues, including human breast. Therefore, future examination of ER signal transduction and/or measurement of ER protein must take into account variant ER expression. The functions of variant ER proteins, either physiological or pathological, remain unclear, although a role(s) for some ER variants in breast tumorigenesis and breast cancer progression would be consistent with the accumulated data. Possible tissue specific expression leads to the speculation that ER variants may have a role in tissue specific estrogen action. The following review focuses on the current knowledge available in the scientific literature with respect to the type and characteristics of estrogen receptor variants and mutations that have been identified to occur naturally in tissues and cell lines.     

Agreement of self-reported hormone receptor status with cancer registry data in young breast cancer patients

BackgroundThough breast cancer subtype is a key determinant of treatment choice and prognosis, few studies have assessed breast cancer patients’ knowledge of estrogen and progesterone receptor (ER/PR) status.MethodsWomen diagnosed with invasive breast cancer at age 18–64 years in 2007 were recruited from the Pennsylvania Cancer Registry, and mailed a questionnaire that asked respondents to identify their ER/PR status. There were 2191 respondents included in the analysis. Agreement between self-report and cancer registry ER/PR status was assessed using kappa statistic. Logistic regression was used to assess the association of demographic, socioeconomic, and tumor factors with inaccurate self-report of ER/PR status.ResultsFifty-nine percent of respondents reported ER/PR positive status, 15% reported ER/PR negative status, 17% responded ‘don’t know’, and 9% did not respond. Overall, there was 69% agreement between self-report and cancer registry data, and fair agreement as measured by kappa (0.36). After excluding women who did not know or did not report their ER/PR status, there was 93% agreement, and substantial agreement as measured by kappa (0.76). Women who were older, non-white, less educated, lower income, and had ER/PR negative disease were significantly more likely to inaccurately report their ER/PR status.ConclusionsThough a significant proportion of women do not know their hormone receptor status, women who reported their ER/PR status were accurate. Our results suggest room for improvement in patient knowledge of tumor subtypes, but also that self-reported ER/PR status may be a useful surrogate when medical record or cancer registry data is unavailable.     

Identification of oestrogen,progesterone receptor and human epidermal growth factor receptor 2 expression in mediastinal metastases of breast cancer obtained by endobronchial ultrasound‐guided transbronchial needle aspiration

Background

In breast cancer patients, the expression statuses of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are crucial in the choice of treatment. Receptor expression in metastatic lesions can differ from the primary tumour. The aim of our study was to analyse the utility of endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) to obtain samples allowing the identification of ER, PR and HER2 expression in patients with mediastinal metastases of breast cancer.

Patients and methods

The clinical files of all patients with a final diagnosis of breast cancer mediastinal metastases diagnosed by EBUS‐TBNA in our institution were retrospectively analysed. The ability of EBUS‐TBNA to obtain samples that allowed hormone receptor and HER2 expression analysis was calculated.

Results

Twenty‐four patients were included. ER, PR and HER2 assessments could be performed in 22, 20 and 22 patients, respectively. In 20 of the 24 patients it was possible to investigate all three types of receptor expression. In the remaining four cases, where ER, PR or HER2 expression tests could not be performed, it was due to a lack of tissue. In cases with adequate results for EBUS‐TBNA and the primary tumour agreement was greater for ER (16/19) and HER2 (12/14) than PR (8/17). Based on receptor status, there was a change in the choice of treatment for five patients.

Conclusion

In patients with breast cancer mediastinal metastases, ER, PR and HER2 expression can be assessed in samples obtained by EBUS‐TBNA whenever a sufficient tissue sample is collected.     

Immunochemistry for oestrogen receptor,progesterone receptor and HER2 on cell blocks in primary breast carcinoma

K. Kumar S, N. Gupta, A. Rajwanshi, K. Joshi and G. Singh Immunochemistry for oestrogen receptor, progesterone receptor and HER2 on cell blocks in primary breast carcinoma Objective: Steroid receptors and human epidermal growth receptor 2 (HER2) have been used for predicting response to treatment in breast cancers. Fine needle aspiration cytology can provide highly cellular material and can be used for such analysis. The present study was undertaken to assess the reliability of oestrogen and progesterone receptor (ER, PR) status and HER2 as demonstrated by immunochemistry (IHC) on cell blocks from breast carcinoma cases, in comparison with histological sections. Methods: IHC for ER, PR and HER2 was performed on cell blocks and their corresponding tissue sections of 50 primary pre‐chemotherapy breast carcinomas. Positivity for ER and PR was scored according to the Allred scoring system. Strong membranous positivity in more than 30% of tumour cells was considered positive for HER2. The tumours were classified as luminal A, luminal B, HER2‐over‐expressing and triple negative on the basis of ER, PR and HER2 status and results on cell blocks compared with histological sections. Results: Correlation between immunostaining on cell blocks and the corresponding tumour tissues revealed a concordance rate for ER, PR and HER2 of 90% [Correlation coefficient (r) = 0.79], 94% (r = 0.86) and 90% (r = 0.76), respectively. Including five cases in which cell blocks were either ER or PR positive, 43/50 cases (86.0%) could be correctly classified on cell block immunostaining alone. The main reasons for seven discordant cases included technical errors (sampling error and staining error) and interpretational error in HER2 evaluation on cell blocks; the core biopsy was inadequate in one, and apparently false negative for HER2 in another. Conclusion: Cell blocks are useful in the assessment of hormone receptor status and HER2 by IHC, especially in cases of locally advanced breast cancer for planning neoadjuvant chemotherapy. It is highly recommended to have good quality cell blocks and quality control of their interpretation.     

Aberrant oestrogen receptor species in human meningioma tissue.

Meningiomas are very rich in progestin receptors (PR) whereas oestrogen receptors (ER) are seldomly found and only at low concentrations. These tumours might possess an ER which is defective in oestrogen binding but still functional in stimulating oestrogen-responsive genes such as PR. In human meningiomas a polymerase chain reaction fragment including the DNA binding domain, the hinge region and the ligand binding domain of ER was amplified. The size of the fragment obtained was as expected from wild type mRNA sequences. Moreover, a variant, which was overexpressed in meningiomas, with a major deletion in exons 2-6 was detected.