Negative estrogen-receptor invasive breast carcinoma: mammographic aspects, correlations with HER2/neu oncoprotein status.

This study involved 40 ER-negative female patients with invasive breast cancer, aged between 25 and 88 years, diagnosed at Emergency County Hospital of Craiova, Romania, during a two-year interval (2010-2011). All patients that took part in the study were subjected to a preoperative mammography exam, and later to HP and IHC exams, in order to detect the ER, PR and HER2 status. These exams were followed by CISH in ambiguous HER2 cases. The tumor detection method was palpation in 16 cases, whereas in 24 cases the method used was the screening mammography. Histopathologically, the analyzed tumors were infiltrative ductal carcinoma (35 cases), lobular carcinoma (one case), mucinous (two cases) and metaplastic carcinoma (two cases). Depending on the status of the oncoprotein HER2, the 40 ER-negative female patients included in the study formed two groups: the ER-negative, HER2-positive (11 cases, 27.5%) formed the first group and the ER-negative, HER2-negative (29 cases, 72.5%) formed the second group. Depending on the expression of the receptors for progesterone, 60% of cases were classified as triple negative mammary carcinomas (ER-, PR-, HER2-). The comparative study of the ER-negative, HER2-positive and the ER-negative, HER2-negative mammary carcinomas showed that the tumors of the ER-negative, HER2-positive group were mostly high degree cancers (80% vs. 56%), with negative progesterone receptors (81.81% vs. 48.27%), associated with axillary lymph node metastasis (63.63% vs. 48.27%), and were detected at a higher cancer stage (II/III) (81.81% vs. 62.06%). Regarding the mammographic features, the ER-negative HER2-positive breast cancers are more likely to be irregular masses (62.5% vs. 33.33%), with spiculated margins (45.45% vs. 6.9%), frequently associated with dense or heterogeneously dense breast (82% vs. 69%) and pleomorphic calcifications (62.5% vs. 28.57%) comparative with ER-negative HER2-negative cancers that were more frequently round/oval mass, with indistinct margins and a great variety of morphological types of calcifications. The correlations between imaging and clinical aspects, together with the biomarker expression in breast cancers may sooner suggest the biological characteristics of these tumors, thus hinting at their evolution and helping to identify female patients with invasive breast cancer that will positively respond to an aimed therapy.

Invasive mammary carcinoma: assessment of HER-2/neu status by immunohistochemistry.

HER-2/neu oncoprotein overexpression in breast cancer patients has an impact on prognosis and treatment methods so assessment of its status is therefore much needed. The study group consisted of 90 cases of mammary invasive carcinoma. The distribution of HER-2/neu immunoexpression for scores 0, 1+, 2+ and 3+ were 54.44%, 11.11%, 18.8% and 15.56% respectively. HER-2/neu -positive cases comprised 21.42% of patients less than 50-year-old compared to 14.47% of patients of 50-year-old or older. Tumor size was negative correlated with HER-2/neu immunoexpression: positive tumors comprised 37.5% of tumor larger than 5 cm and this percentage decreases with tumor dimension to 2.94% in tumors of 2 cm or less. Regarding the histopathological subtype of invasive mammary carcinoma, only some types were positive, like 17.57% of IDC NOS and one case of mixed ductal-lobular invasive carcinoma. The highest proportion (21.31%) of positive HER-2/neu cases presented high-grade carcinomas (GIII), comparing with well-differentiated (GI) that were all negative. Regarding the axillary lymph node status the lowest proportion of positive HER-2/neu cases was 4.54% in the absence of metastasis, and rises to 34.78% in cases with more than three axillary lymph nodes involved. HER-2/neu-positive tumors showed a low incidence of ER+ or PR+ cases unlike HER-2/neu -negative cases (35.71% vs. 83.05% for ER, respective 21.42% vs. 76.27% for PR). Therefore, in conclusion, HER-2/neu-positive tumors are significantly fewer than the negative ones, but these are found in younger women and are associated with: large tumor size, high grade of malignancy (GIII) and increased number of axillary lymph node involvement. HER-2/neu immunoexpression is related to histological subtype of invasive breast carcinomas. Hormonal status is negative related to HER-2/neu expression.

Immunohistochemical evaluation of hormone receptors with predictive value in mammary carcinomas.

AIM: Immunohistochemical evaluation of hormone receptors (ER, PR) and correlation of immunohistochemical and morpho-clinical data. MATERIALS AND METHODS: The study was performed on paraffin-embedded and HE-stained tissues originating from 100 cases of invasive mammary carcinoma. Monoclonal antibodies, anti-estrogen and anti-progesterone receptors, were used for the immunohistochemical study. The detection system was EnVision HRP and the visualization system was 3,3'-diaminobenzidine tetrahydrochloride (DAB). The evaluation of the result was performed using the Allred score. RESULTS: The majority of the studied cases (57%) expressed both types of hormone receptors and in 32% of the cases the hormone receptors were completely absent. The rest of the cases presented a heterogeneous phenotype: 7% presented the ER-÷PR+ phenotype and 4% the ER+÷PR- phenotype. Compared with the classical phenotype (ER+÷PR-), ER+÷PR- tumors were more frequent at patients over 50-year-old. The tumors with ER+÷PR- were larger than the ER+÷PR+ and they were of the invasive ductal carcinoma type with an Allred score for ER under 6. CONCLUSIONS: The predictive value is amplified when the ER status is correlated with the PR status because the heterogeneous phenotypes are identified, especially the ER+÷PR- phenotype, which have an aggressive behavior and the lowest response to tamoxifen therapy.

Vertebral bone metastasis in breast cancer: a case report.

BACKGROUND: We report here a case of a 66-year-old woman with a very aggressive form of breast carcinoma, having both liver and bone dissemination points. CASE DESCRIPTION: The patient was admitted for a rapid onset disk-herniation-like syndrome, but which on further investigation proved to be in fact a metastatic case of breast cancer. We found evidence of disseminations at least in the lumbar vertebral bodies and the liver. Pathological analysis of the available vertebral metastasis revealed a HER2+ molecular pattern, accordingly to the newly evolving molecular typing of breast cancers. Despite a rapid treatment instauration, the patient reacted poorly to taxanes and octeoclast inhibitors, and died after less than 11 months from admitting to the hospital. CONCLUSIONS: This is a rare case of an aggressive breast carcinoma identified initially after the vertebral metastases themselves that induced a non-specific symptomatology.

Immunohistochemical study of p53 and Ki67 in a group of patients with mammary carcinoma.

The study was done over a period of 10 years, 1996-2005 and it included 562 mammary cancer patients. Of the 562 cases, 100 cases of invasive mammary carcinoma included in this study were investigated from an immunohistochemical point of view. The p53 overexpression was more frequently seen in patients under 50 (23 cases, that is 54.76%), compared to those over 50 years old (19 cases, that is 45.24%). The positive p53 tumors were more often over 2 cm big. The invasive ductal carcinomas were p53-positive in 40 cases (44.44%) of all invasive ductal carcinoma cases, and the invasive lobular carcinomas were only positive in two cases (20%) of all mammary invasive lobular carcinoma cases. Most cases that had the overexpression of the p53-protein (30 cases that is 71.43%) had a high histological degree (G3), and only 12 cases (28.57%) had a low histological degree (G1 and G2). The overexpression of the p53-protein was present in all cases that had a heterogeneous phenotype (with one of the hormonal receptors being negative), in over half of the cases that had both hormonal receptors negative (59.37% of ER-/PR- phenotype cases) and in only 21.05% of cases that had ER+/PR+ phenotype. The association of the p53 overexpression (p53 over 10%), with the HER2 (2+ or 3+ score) overexpression was seen in seven patients of the 100 invasive mammary carcinoma cases included in this study. Consequently, 16.66% of p53 positive cases had associated positivity for HER2. Most cases that were p53 positive had an increased proliferation activity, as determined with Ki67. The Ki67 immunostaining analysis has made it clear that this marker has positivity presence in all cases. The vast majority of cases had a nuclear marking to Ki67, but two cases (2% of cases) had a cytoplasmatic / membrane staining.

Cytological and histopathological aspects concerning preinvasive squamous cervical lesions.

Our study was carried out on a total number of 158 patients, with a mean age of 32, all tested and identified cytologically (Pap-test) as presenting minor cellular abnormalities, respectively ASCUS (10) and LSIL (119), and major cellular abnormalities, respectively SIL-borderline (8) and HSIL (21), and who, either voluntarily or upon cytopathologists' recommendation, were colposcopically examined. Subsequently, they were subjected to cervical biopsy or excision therapy. In patients with ASCUS cytology, 6 cases were morphologically diagnosed with benign cervical lesions, 3 were diagnosed with LSIL, and one patient was diagnosed as HSIL (CIN 2). Out of 119 LSIL smears 108 were confirmed by histopathology, while 11 were diagnosed as HSIL (CIN 2). In SIL-borderline patients, 5 cases were screened as LSIL and 3 as HSIL. In patients with HSIL cytology, 18 were diagnosed histopathologically as HSIL (CIN 2 and CIN 3/CIS), while 3 were diagnosed as invasive squamous carcinoma.

Immunohistochemical evaluation of hormone receptors with predictive value in mammary carcinomas.

AIMS. Immunohistochemical evaluation of hormone receptors (ER, PR) and correlation of immunohistochemical and morpho-clinical data. METHOD. The study was performed on paraffin-embedded and HE stained tissues originating from 100 cases of invasive mammary carcinoma. Monoclonal antibodies anti-estrogen and anti progesterone receptors were used for the immunohistochemical study. The detection system was EnVision HRP and the visualization system was 3-3' diaminobenzidine tetrahydrochloride (DAB). The evaluation of the result was performed using the Allred score. REZULTS. The majority of the studied cases (57%) expressed both types of hormone receptors and in 32% of the cases the hormone receptors were completely absent. The rest of the cases presented a heterogeneous phenotype: 7% presented the ER-/PR+ type and 4%, the ER+/PR- type. Compared with the classical phenotype (ER+/PR-), ER+/PR- tumors were more frequent at patients over 50 years. The tumors with ER+/PR- were larger than the ER+/PR+ and they were of the invasive ductal carcinoma type with an Allred score for ER under 6. CONCLUSION. The predictive value is amplified when the ER status is correlated with the PR status because the heterogeneous phenotypes are identified, especially the ER+/PR- phenotype which have an aggressive behavior and the lowest response to tamoxifen therapy.

Accelerated infarct development, cytogenesis and apoptosis following transient cerebral ischemia in aged rats.

Old age is associated with a deficient recovery from stroke, but the cellular mechanisms underlying such phenomena are poorly understood. To address this issue, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. Aged rats showed a delayed and suboptimal functional recovery in the post-stroke period. Using BrdU-labeling, quantitative immunohistochemistry and 3-D reconstruction of confocal images, we found that aged rats are predisposed to rapidly develop an infarct within the first few days after ischemia. The emergence of the necrotic zone is associated with a high rate of cellular degeneration, premature accumulation of proliferating BrdU-positive cells that appear to emanate from capillaries in the infarcted area, and a large number of apoptotic cells. With double labeling techniques, we were able to identify, for the first time, over 60% of BrdU-positive cells either as reactive microglia (45%), oligodendrocyte progenitors (17%), astrocytes (23%), CD8+ lymphocytes (4%), or apoptotic cells (<1%). Paradoxically, despite a robust reactive phenotype of microglia and astrocytes in aged rats, at 1-week post-stroke, the number of proliferating microglia and astrocytes was lower in aged rats than in young rats. Our data indicate that aging is associated with rapid infarct development and a poor prognosis for full recovery from stroke that is correlated with premature cellular proliferation and increased cellular degeneration and apoptosis in the infarcted area.