Reappraisal of immunohistochemical profiling of special histological types of breast carcinomas: a study of 121 cases of eight different subtypes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Palladium(II) Complexes with Thiosemicarbazones. Syntheses, Characterization and Cytotoxicity against Breast Cancer Cells and Anti-Mycobacterium tuberculosis Activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

An immunohistochemical study of interleukin-8 (IL-8) in breast cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

An unusual case of malignant cystosarcoma phyllodes of the breast

A unusually large tumor of the left breast diagnosed as a cystosarcoma phyllodes with multiple malignant sarcomatous changes of the stroma, consisting of liposarcoma, myxoid fibrosarcoma, anaplastic, and giant cell sarcoma is described. The weight of 6200 g (13.5 lb) seems to be the largest so far presented in the literature reviewed by the authors. © 1986.

Carcinoid tumour of male breast diagnosed by fine needle aspiration.

A primary carcinoid tumour of the breast in a 66-year-old man was diagnosed by fine-needle aspiration cytology. The nature of the lesion was proved by histochemical and immunocytochemical studies. The importance of a conclusive diagnosis is discussed and the value of immunocytochemical analysis as an aid to cytomorphologic diagnosis is demonstrated.

Detection of estrogen receptor in formalin-fixed and paraffin-embedded breast carcinoma: correlation with histological patterns.

The authors studied the expression of estrogen receptor (ER) in tissues of breast carcinomas which were previously fixed in formalin and paraffin-embedded. The ER expression was correlated with several histological findings, namely grade of differentiation, tumor necrosis, desmoplasia, lymphocytic infiltration and elastosis. The ER was detected in tissues using the avidin-biotin immunoperoxidase technique associated with the H222 monoclonal antibody from Abbott. All 39 biopsies were of infiltrating ductal carcinoma of breast and 16 of them expressed ER. The statistical analysis showed that the expression of ER was correlated with histological findings of good prognosis as well differentiated carcinomas, no tumor necrosis, absence or mild lymphocytic infiltration around the tumor cells and severe elastosis.

Simple mucin-type carbohydrate antigens (T, sialosyl T, Tn and sialosyl-Tn) in breast carcinogenesis

Immunohistochemical analysis of the expression of simple mucin-type carbohydrate antigens (Tn, sialyl-Tn and T) was performed in a series of 43 cases of intraductal hyperplasia without atypia, 9 cases of intraductal hyperplasia with atypia, 54 cases of ductal carcinoma in situ (DCIS) and 26 cases of invasive breast carcinoma. We also studied 36 cases of isolated breast normal epithelium, 20 cases of 'normal' breast epithelium adjacent to neoplasms and 14 cases of apocrine metaplasia. All antigens were detected in different frequencies in normal, hyperplastic, metaplastic and neoplastic breast epithelium. Tn and sialyl-Tn are expressed more frequently in malignant than in benign breast epithelium; while Tn expression increases from normal to invasive carcinomas, sialyl-Tn increases until DCIS and drops in invasive carcinomas, suggesting that either there is a failure of a proportion of DCIS to progress to invasive carcinoma or loss of expression of sialyl-Tn when some carcinomas become invasive. The high frequency of Tn and sialyl-Tn expression in breast intraductal proliferations probably reflects incomplete glycosylation in these lesions, which is a well-known tumour-associated phenomenon and supports the assumption that such lesions are putative precursors of breast cancer. T antigen was expressed in all groups studied, but its prevalence differed significantly between normal and neoplastic epithelium. The expression of these antigens in epithelium adjacent to carcinomas is similar to that found in isolated normal breast epithelium, whereas apocrine metaplasia has a pattern of simple mucin-type glycosylation that is specific and distinct from that of the normal breast epithelium, with a high frequency of marked expression of Tn and sialyl-Tn. The similarity of the pattern of expression of simple mucin-type antigens in metaplasia and malignant neoplasia reduces the usefulness of these markers from a diagnostic standpoint.

Cytogenetic evaluation of 20 primary breast carcinomas

Chromosome analysis was performed on samples from 20 Brazilian patients with breast cancer. All the samples were from untreated patients who presented the clinical symptoms for months or years before surgical intervention. Six cases showed axillary lymph node metastases. Clonal chromosome abnormalities were detected in all cases. The numerical alterations most frequently observed involved the loss of chromosomes X, 19, 20, and 22 followed by gain of chromosomes 9 and 8. Among the structural anomalies observed, there was preferential involvement of chromosomes 11, 6, 1, 7, 3, and 12, supporting previous reports that these chromosomes may harbour genes of importance in the development of breast tumors. Two cases with a family history of breast cancer had in common total or partial trisomy 1.

Correlation between carotenoid concentrations in serum and normal breast adipose tissue of women with benign breast tumor or breast cancer

To evaluate the relationship between carotenoid concentrations in serum and breast tissue, we measured serum carotenoid concentrations and endogenous carotenoid levels in breast adipose tissue of women with benign breast tumor (n = 46) or breast cancer (n = 44). Before extraction, serum was digested with lipase and cholesterol esterase, and breast adipose tissue was saponified. Serum and tissue carotenoids were extracted with ether/hexane and measured by using HPLC with a C30 column. Serum retinoic acid was extracted with chloroform/methanol and measured using HPLC with a C18 column. There were no significant differences in serum carotenoids [lutein, zeaxanthin, cryptoxanthin (both α- and β-), α-carotene, all-trans β-carotene, 13-cis β-carotene and lycopene], retinoids (retinol, all-trans and 13-cis retinoic acids), and α- and -γ- tocopherol concentrations between benign breast tumor patients and breast cancer patients. A substantial amount of 9-cis β- carotene was present in adipose tissue and was the only carotenoid that had a significantly lower level in benign breast tumor patients than in breast cancer patients. Correlations between carotenoid concentrations in serum and in breast adipose tissue were determined by combining the data of the two groups. Concentrations of the major serum carotenoids except cryptoxanthin showed significant correlations with breast adipose tissue carotenoid levels. When the concentrations of serum carotenoids were adjusted for serum triglycerides or LDL, correlations between serum carotenoid concentrations and breast adipose tissue carotenoid levels markedly increased, including that of cryptoxanthin (P <0.001). The strong correlation between serum carotenoid concentrations and endogenous breast adipose tissue carotenoid levels indicate that dietary intake influences adipose tissue carotenoid levels as well as serum concentrations, and that adipose tissue is a dynamic reservoir of fat-soluble nutrients.

Tamoxifen down-regulates CaMKII messenger RNA levels in normal human breast tissue

Tamoxifen was proven to reduce the incidence of breast cancer by 49% in women at increased risk of the disease in the Breast Cancer Prevention Trial. In order to identify potential candidates to explain the preventive effect induced by tamoxifen on breast cancer, normal breast tissue obtained from 42 fibroadenoma patients, randomly assigned to receive placebo or tamoxifen, was analyzed by the reverse Northern blot and RT-PCR techniques. The cDNA fragments used on Northern blot membranes were generated by the Human Cancer Genome Project funded by the Ludwig Institute for Cancer Research and FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil). Total RNA was obtained from normal breast tissue from patients with clinical, cytological and ultrasound diagnosis of fibroadenoma. After a 50-day treatment with tamoxifen (10 or 20 mg/day) or placebo, normal breast tissue adjacent to the tumor was collected during lumpectomy with local anesthesia. One differentially expressed gene, Calcium/calmodulin-dependent protein kinase II (CaMKII), was found to be down-regulated during TAM treatment. CaMKII is an ubiquitous serine/threonine protein kinase that has been implicated in the diverse effects of hormones utilizing Ca2+ as a second messenger as well as in c-fos activation. These results indicate that the down-regulation of CaMKII induced by TAM might represent alternative or additional mechanisms of the action of this drug on cell cycle control and response to hormones in normal human breast tissue.

Shorter CAG repeat in the AR gene is associated with atypical hyperplasia and breast carcinoma

Background: Previous reports into the role of [CAG]n repeat lengths in the androgen receptor (AR) gene indicate that these may play an important part in the development and progression of breast cancer, however, knowledge regarding benign breast lesions is limited. Patients and Methods: PCR-based GeneScan analysis was used to investigate the [CAG]n repeat length at exon 1 of the AR gene in 59 benign breast lesions (27 fibroadenomas, 18 atypical hyperplasias, and 14 hyperplasias without atypia) and 54 ductal breast carcinomas. Seventy-two cancer-free women were used as a control group. In addition, [CAG]n repeats were evaluated for the presence of loss of heterozygosity (LOH) and microsatellite instability (MSI) in a subset of these samples (27 fibroadenomas, 14 hyperplasias without atypia and 22 breast carcinomas). Results: Shorter [CAG]n repeat lengths were strongly correlated with atypical hyperplasias (p=0.0209) and carcinomas (p<0.0001). LOH was found in 1/12 and 4/20 informative cases of hyperplasias without atypia and breast carcinomas, respectively. Three patients with breast carcinoma who had previously presented atypical hyperplasia showed a reduction in the [CAG]n repeat length in their carcinomas. Conclusion: Short [CAG]n repeat length (≤20) polymorphisms are strongly associated with breast carcinomas and atypical hyperplasias. Although non-significant, a subgroup of patients with breast carcinoma and genotype SS showed an association with parameters of worse outcome.

Association between breast-feeding practices and sucking habits: A cross-sectional study of children in their first year of life

In addition to providing nutrition and immunological protection, breast-feeding has positive effects on the development of the infant's oral cavity. The aim of the present study is to assess breast-feeding patterns and to analyze the influence of breast-feeding practices and maternal sociodemographic variables on the prevalence of non-nutritive sucking habits in a sample of Brazilian infants. This cross-sectional study was carried out in Southern Brazil. A random sample of 100 mothers of infants up to 12 months of age was interviewed during the National Vaccination Campaign Day. The prevalence and median duration of breast-feeding were assessed. Breast-feeding practice, the exposure factor, was categorized as exclusive breast-feeding, predominant breast-feeding, complementary breast-feeding, or weaning. Maternal sociodemographic variables included age, race, marital status, educational level, profession, and family income. The outcome investigated was the prevalence of sucking habits (pacifier use and thumb sucking). We used two-sample tests, the chi-square test and Fisher exact test0 for statistical analyses of the data. The study revealed that 75% of infants were being breast-fed. Pacifier use and thumb sucking were common in 55%. Bottle-feeding was prevalent in 74% of infants. Breast-feeding was negatively correlated with pacifier use and thumb sucking (OR = 0.11; 95% CI: 0.03 to 0.4). Bottle-feeding was strongly associated with weaning (p = 0.0003). Among the sociodemographic variables, only marital status showed a statistical association with sucking habits (p = 0.04). These findings suggest that breast-feeding can prevent the occurrence of sucking habits. Although we could not evaluate causality assessment, malocclusion prevention seems to be yet one more reason for promoting breast-feeding practices.

Tamoxifen inhibits transforming growth factor-α gene expression in human breast carcinoma samples treated with triiodothyronine

Objectives: To examine the effects of triiodothyronine (T3), 17β-estradiol (E2), and tamoxifen (TAM) on transforming growth factor (TGF)-α gene expression in primary breast cancer cell cultures and interactions between the different treatments. Methods and results: Patients included in the study (no.=12) had been newly diagnosed with breast cancer. Fresh human breast carcinoma tissue was cut into 0.3-mm slices. These slices were placed in six 35-mm dishes on 2-ml organ culture medium. Dishes received the following treatments: dish 1: ethanol; dish 2: T3; dish 3: T3+TAM; dish 4: TAM; dish 5: E2; dish 6: E2+TAM. TGF-α mRNA content was normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA levels. All tissues included in this study were positive for estrogen receptor (ER) and thyroid hormone receptor expression. Treatment with T3 for 48 h significantly increased TGF-α mRNA levels compared to controls (15-fold), and concomitant treatment with TAM reduced expression to 3.4-fold compared to controls. When only TAM was added to the culture medium, TGF-α mRNA expression increased 5.3-fold, significantly higher than with all other treatment modalities. Conclusion: We demonstrate that TGF-α mRNA expression is more efficiently upregulated by T3 than E2. Concomitant treatment with TAM had a mitigating effect on the T3 effect, while E2 induced TGF-α upregulation. Our findings show some similarities between primary culture and breast cancer cell lines, but also some important differences: a) induction of TGF-α, a mitogenic protein, by TAM; b) a differential effect of TAM that may depend on relative expression of ER α and β; and c) supraphysiological doses of T3 may induce mitogenic signals in breast cancer tissue under conditions of low circulating E2. ©2008, Editrice Kurtis.