Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk.

BACKGROUND: Several studies have reported that the insulin-like growth factor 1 (IGF-1) is positively associated with estrogen receptor-positive [ER(+)] breast cancer risk, whereas there is little or no association with respect to ER(-) breast cancer. All comparisons of ER(+) breast cancer cases, however, have been made versus healthy controls, for whom there is no information about the ER expression in their mammary gland. PATIENTS AND METHODS: In the context of a case-control investigation conducted in Athens, Greece, we studied 102 women with incident ERα(+) breast cancer and compared their IGF-1 blood levels with those of 178 ERα(+) and 83 ERα(-) women with benign breast disease (BBD) who underwent biopsies in the context of their standard medical care. Data were analysed using multiple logistic regression and controlling for potential confounding variables. RESULTS: ERα(+) breast cancer patients had higher IGF-1 levels compared with women with BBD [odds ratio (OR) 1.36, 95% confidence interval (CI): 0.95-1.94, per 1 standard deviation (SD) increase in IGF-1 levels]. When ERα status of women with BBD was taken into account, the difference in IGF-1 levels between ERα(+) breast cancer patients and women with BBD was clearly driven by the comparison with BBD women who were ERα(+) (OR = 1.95, 95% CI: 1.31-2.89 per 1 SD increase in IGF-1 levels), whereas there was essentially no association with IGF-1 levels when ERα(+) breast cancer patients were compared with ERα(-) BBD women. These contrasts were particularly evident among post/peri-menopausal women. CONCLUSIONS: We found evidence in support of an interaction of IGF-1 with the expression of ERα in the non-malignant mammary tissue in the context of breast cancer pathogenesis. This is in line with previous evidence suggesting that IGF-1 increases the risk of ER(+) breast cancer.

Calcium sensing receptor in pregnancies complicated by gestational diabetes mellitus.

INTRODUCTION: Infants born from mothers with Gestational diabetes mellitus (GDM) experience several complications, including a higher rate of postnatal hypocalcemia. In this study, we investigated the association between calcium sensing receptor (CaSR) and neonatal hypocalcemia observed in GDM pregnancies. METHODS: Our study consisted of 58 pregnant women with GDM and 40 healthy women and their neonates. CaSR placental expression was evaluated with immunohistochemistry and Western Blot. Three CaSR single nucleotide polymorphisms, A986S, R990G, Q1011E, were evaluated in neonate's genomic DNA. Serum Ca, P, Mg, 25(OH)D and PTH were measured in cord blood and at 2nd day of life. RESULTS: GDM neonates had lower mean cord blood Ca levels than controls (2.47 ± 0.21 mmol/l vs 2.59 ± 0.13 mmol/l, p = 0.001) while 15.5% developed postnatal hypocalcemia. CaSR expression was lower in GDM than in healthy placentas (p < 0.001). In the GDM group, reduced CaSR immunostaining in the syncytiotrophoblast (p = 0.042) and extravillous cytotrophoblasts (p = 0.002) was associated with lower Ca cord blood levels. Moreover, the absence of the S allele of the A986S polymorphism was associated with lower serum Ca levels both at birth (AA:2.41 ± 0.23 mmol/l, AS + SS: 2.57 ± 0.12 mmol/l, p = 0.002) and at 2nd day of life (AA:2.05 ± 0.22 mmol/l, AS + SS: 2.20 ± 0.18 mmol/l, p = 0.019). CONCLUSIONS: Our results showed that CaSR is under-expressed in GDM compared with healthy placentas and this alteration may be associated with the lower Ca levels measured in cord blood of GDM infants. Placental CaSR seems to exert a local effect in fetal Ca homeostasis, which is dissociated from its contribution to the regulation of Ca homeostasis in postnatal life.

Breast cancer characterization based on image classification of tissue sections visualized under low magnification.

Rapid assessment of tissue biopsies is a critical issue in modern histopathology. For breast cancer diagnosis, the shape of the nuclei and the architectural pattern of the tissue are evaluated under high and low magnifications, respectively. In this study, we focus on the development of a pattern classification system for the assessment of breast cancer images captured under low magnification (×10). Sixty-five regions of interest were selected from 60 images of breast cancer tissue sections. Texture analysis provided 30 textural features per image. Three different pattern recognition algorithms were employed (kNN, SVM, and PNN) for classifying the images into three malignancy grades: I-III. The classifiers were validated with leave-one-out (training) and cross-validation (testing) modes. The average discrimination efficiency of the kNN, SVM, and PNN classifiers in the training mode was close to 97%, 95%, and 97%, respectively, whereas in the test mode, the average classification accuracy achieved was 86%, 85%, and 90%, respectively. Assessment of breast cancer tissue sections could be applied in complex large-scale images using textural features and pattern classifiers. The proposed technique provides several benefits, such as speed of analysis and automation, and could potentially replace the laborious task of visual examination.

A comparison of hormonal profiles between breast cancer and benign breast disease: a case-control study.

BACKGROUND: Benign breast disease (BBD), particularly proliferative BBD, is an established breast cancer risk factor. However, there has been no systematic attempt to compare the hormonal profiles of the two conditions. In a case-control investigation in Athens, Greece, we compared levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1), as well as their principal binding proteins, between breast cancer patients, women with BBD by histological type (proliferative and nonproliferative) and women with no breast pathology. PATIENTS AND METHODS: We studied 466 women with incident breast cancer, 704 women with BBD and 244 healthy women. We used multiple regression to compare log-transformed serum hormone levels of breast cancer patients with those of healthy women and women with BBD by histological type (proliferative and nonproliferative BBD). RESULTS: The hormonal profile of breast cancer in our study was in line with the generally accepted hormonal profile of this disease, as reported from large cohort studies. Compared with healthy women, breast cancer patients tended to have higher levels of steroid hormones. The evidence was strong for estrone (difference 21.5%, P < 0.001), weaker for testosterone (difference 15.8%, P = 0.07) and weaker still for estradiol (difference 12.0%, P = 0.18). Also compared with healthy women, breast cancer patients had barely higher levels of IGF-1 (difference 2.0%, P = 0.51), but had significantly lower levels of IGF binding protein 3 (IGFBP-3) (difference -6.7%, P = 0.001). Compared with women with BBD, breast cancer patients had nonstatistically significantly lower levels of steroid hormones, but they had higher levels of IGF-1 [difference 5.5%, 95% confidence interval (CI) 0.7% to 10.6%] and lower levels of IGFBP-3 (difference -3.7%, 95% CI -6.7% to -0.7%). Differences were more pronounced when breast cancer patients were contrasted to women with proliferative BBD. CONCLUSIONS: Our findings suggest that high levels of IGF-1 may be an important factor toward the evolution of BBD to breast cancer.

The hormonal profile of benign breast disease.

BACKGROUND: Limited information exists about the endocrine milieu of benign breast disease (BBD), a documented breast cancer risk factor. We compared blood levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1) between BBD patients by histological type and women without breast pathology. METHODS: We studied 578 BBD patients and 178 healthy women in Athens, Greece, who provided blood samples, and completed interviewer-administered questionnaires. RESULTS: Of the BBD patients, 254 had non-proliferative disease, 268 proliferative disease without atypia and 56 atypical hyperplasia. Comparing BBD patients with healthy women, the per cent differences (and 95% confidence intervals) for blood hormones, among pre-menopausal and peri/post-menopausal women, respectively, were: 22.4% (-4.0%, 56.1%) and 32.0% (5.6%, 65.1%) for estradiol; 26.2% (10.1%, 44.8%) and 30.9% (16.8%, 46.6%) for estrone; 19.5% (3.1%, 38.4%) and 16.5% (-5.0%, 42.9%) for testosterone; and -5.2% (-13.8%, 4.4%) and -12.1% (-19.8%, -3.6%) for IGF-1. Steroid hormones tended to be higher in proliferative compared with non-proliferative BBD. CONCLUSIONS: Circulating steroid hormones tend to be higher among women with BBD than women with no breast pathology and higher in proliferative than non-proliferative disease; these patterns are more evident among peri/post-menopausal women. In peri/post-menopausal women IGF-1 was lower among women with BBD compared with healthy women.

Histopathological changes induced by therapies in the benign prostate and prostate adenocarcinoma.

The effect of androgen deprivation and other hormonal therapies, radiation therapy, thermal ablation therapies, chemotherapy, and other systemic treatments is evident in the histology of non-neoplastic and neoplastic human prostate gland. Androgen deprivation may be achieved with: a. orchidectomy, b. exogenous oestrogen administration, c. drugs with the capacity to deplete the hypothalamus of luteinizing hormone-releasing hormone, d. antiandrogens administration: drugs, which block the conversion of testosterone to its active form of 5-alpha dihydrotestosterone (i.e. finasteride, dutasteride), and drugs which block the androgen receptor on individual cells (i.e. flutamide). Androgen deprivation therapies cause atrophy of non-neoplastic and neoplastic prostatic epithelium, as the result of apoptosis, and are mainly used as a palliative measure in metastatic prostate cancer or as neoadjuvant or adjuvant treatment, in clinically localized prostate cancer. Morphological tumour regression may complicate the recognition and grading of treated carcinomas in radical prostatectomy specimens. Radiation therapy may be applied in the form of external beam, interstitial implantation (brachytherapy), or a combination, as a mainstay or adjuvant (external beam) treatment in localized prostate cancer. The primary effect is the damage of endothelial cells, which cause ischemia that leads to atrophy. The difficulty of post-radiation prostate needle biopsy interpretation includes the distinction of treatment effect in normal prostatic tissue from recurrent or residual tumour. Histological changes after thermal ablation mainly include lesions observed in prostatic infarcts due to periurethral coagulative type necrosis of variable volume. The correlation between the histopathological effects of the above therapies and their clinical significance is not absolutely clear.