From conventional pathologic diagnosis to the molecular classification of breast carcinoma: are we ready for the change?

Breast cancer is the most frequent malignant tumor in women and the diagnosis, prognosis and therapeutic strategy are based on the pathologic report. In last years, it was shown that conventional pathologic diagnosis brings few data about prognosis and tells nothing about the response of the tumor to specific therapy. In an effort to improve the molecular characterization of breast cancer, gene profile analysis was performed in a large number of cases. Based on this analysis, there were characterized five molecularly different subclasses: basal-like, luminal type A and B, HER-2, and unclassified. It was shown that prognosis and response to adjuvant therapy is significantly different in these five subtypes. Immunohistochemistry was demonstrated to be a good and acceptable surrogate of the gene analysis. A panel of antibody that includes estrogen receptors (ER), progesterone receptors (PR), Her2 protein, cytokeratin 5 (CK5), epidermal growth factor receptor (EGFR), p53 mutation, and Bcl-2 expression, can discriminate between these five molecular subclasses. In the present review there are presented the main characteristics of the molecular subclasses, the relationships with the conventional pathologic classification, critical problems of the molecular classification and their impact on prognosis and therapy.

E-cadherin expression in invasive breast cancer.

There were investigated 22 cases with invasive breast carcinoma from the archive material, and the immunohistochemical expression of E-cadherin was correlated with clinical stage, pathological type, grade of the tumor, and lymph nodes status. The expression of E-cadherin was assessed by the pattern of the final product of reaction and number of positive cells. The reaction was appreciated as normal if over 70% of tumor cells showed membrane of membrane and cytoplasmic pattern, and aberrant, if less than 70% of tumor cells were positive. There were found 45.5% cases with normal expression and 54.5% with aberrant expression. Strong positive reaction was found mainly in tumor cells invading the adipose tissue, but the reaction was weak or negative in tumor cells within the vessels. Both normal and aberrant expression of E-cadherin correlates with grade and with clinical stage. In our study was found that the increase of the tumor grade is associated with decrease in the expression of E-cadherin. Tumors over 2 cm in their larger diameter showed a decreased expression of E-cadherin. Seventeen from 22 cases with lymph node metastasis had positive reaction in the primary, but there were not found significant differences between the normal and aberrant expression.

Vascular endothelial growth factor A (VEGF A) as individual prognostic factor in invasive breast carcinoma.

VEGF is a potent mitogen for endothelial cells and also acts in an autocrine and paracrine manner for development of tumor cells in breast cancer. Correlations between VEGF and some clinicopathologic findings were largely studied but results were controversial. Our purpose was to find if VEGF could be used as individual prognostic factor in invasive breast carcinoma. We included in our study 35 cases of invasive breast carcinoma, which were immunostained for VEGF using monoclonal antibodies anti-VEGF clone VG1. The assessment of VEGF expression used a scoring system, which included an intensity parameter correlated with percent of positive tumor cells. We found positive correlation between ductal invasive carcinoma type of breast cancer and VEGF expression. In addition, presence of inflammation associated with breast malignancies had a significant correlation with VEGF positive staining. Because of these correlations found in our study, we concluded that VEGF could not be used as individual prognostic factor in invasive breast carcinoma.

Relevance of the immunohistochemical expression of cytokeratin 8/18 for the diagnosis and classification of breast cancer.

PURPOSE: The aim of our study was to characterize and describe the different immunohistochemical expression patterns of cytokeratin 8/18 (CK8/18) in breast tumors and to make a correlation between histopathology, immunohistochemistry for CK8/18 and its possible diagnostic value of this pair of keratins for molecular classification of breast cancers. MATERIAL AND METHODS: Forty cases of breast tumors immunostained with monoclonal antibodies against CK8/18 using a polymer based detection system and diaminobenzidine as chromogen were microscopically evaluated in normal and tumor breast tissue concerning the intensity, distribution and density of positive cells. Association with histopathology and nuclear grade were also studied. RESULTS: Three different models of positive reaction were found: (1) normal cytoplasmic with intense and diffuse pattern, (2) aberrant membrane pattern and (3) aberrant cytoplasmic granular pattern associated with membranous positive reaction. Normal expression of CK8/18 was found in 23 cases of breast cancer, aberrant membranous in nine cases and aberrant with granular pattern in four cases. Further studies will be needed to elucidate these differences and possible correlation with other molecular markers.

[Our experience in the thoracoscopic surgery of the tuberculous pleural effusions]. / Experienta noastra în chirurgia toracoscopica a colectiilor pleurale tuberculoase.

Pleural tuberculosis (TB) is most often treated by a pneumologist. Some cases require operative interventions and may represent a challenge for the thoracic surgeon. There are two specific problems regarding TB pleural effusions: 15-25% of them remain undiagnosed using the conventional methods of diagnosis (imaging, thoracentesis, percutaneous pleural biopsies) and have a tendency for the rapid production of dense adherences and loculations. The authors present their experience in the diagnosis and the treatment of tuberculous pleurisy by means of mini-invasive surgical techniques. The period of study was January 2001-December 2006. In that period, the authors performed 400 video-assisted surgical operations, representing 9% of all the operations carried out in the clinic (3833). The surgical indications were for diagnosis (pleural, pericardial, lung or lymph node biopsy) and for treatment (pleurisy, pleuro-pericarditis, empyema). The contraindications for VATS were the usual ones. 56 cases were diagnosed with pleuro-pulmonary tuberculosis (14% of the VATS). For 43 patients the first approach was strictly thoracoscopic (VATS), while for the rest of 13 we started directly through a minithoracotomy with video assistance. We had 7 conversions to minithoracotomies with video assistance from those 43 aforementioned patients. Minithoracotomy with video assistance was preferred in 13 cases as a primary approach. We used two-port approach in 30 cases and the three-port triangular approach was useful for 6 patients. In 4 cases the bidigital technique was used in order to achieve greater room for exploration. We experienced only one minor intraoperative complication. Our results are comparable to those reported by other authors. The main idea of this paper is that the advantages of VATS in the pathology of the tuberculosis are undeniable.