Assessment of the immunoexpression profile of breast ductal carcinoma with Cyclin D1, Her-2/Neu and p53 at Yangon General Hospital, Myanmar

One hundred cases of histologically proven invasive ductal carcinomas were histologically graded based on modified Bloom and Richardson Grading. Out of these 17 cases each of low grade, intermediate grade, and high grade invasive ductal carcinomas were selected for Immunostaining using the monoclonal antibodies Cyclin D1,pP53 and Her2/neu. It was found that for all three monoclonal antibodies the lowest histological grade of Invasive Ductal Carcinoma of the Breast showed the lowest positivity with Cyclin D1 ( 11.76%) and p53 ( 17.64%) and Her2/neu ( 47.05%). The intermediate grade tumour showed ( 70.58% ) positivity with Cyclin D1 and 58.58 % in p53 and Her2/neu. The high grade invasive ductal carcinoma of the breast showed the highest positivity of Cyclin D1 (76.47%) , p53 (88.24% ) ,Her2/neu ( 94.12% ); These suggest that Cyclin D1 , P53 and Her2/neuimmunoexpression positivity increases with rising histological grades of invasive ductal carcinoma of breast.

De novo and cell line models of human mammary cell transformation reveal an essential role for Yb-1 in multiple stages of human breast cancer

Breast cancer heterogeneity has made it challenging to identify mechanisms critical to the initial stages of their genesis in vivo. Here, we sought to interrogate the role of YB-1 in newly arising human breast cancers as well as in established cell lines. In a first series of experiments, we found that short-hairpin RNA-mediated knockdown of YB-1 in MDA-MB-231 cells blocked both their local tumour-forming and lung-colonising activity in immunodeficient mice. Conversely, upregulated expression of YB-1 enhanced the poor in vivo tumorigenicity of T47D cells. We then found that YB-1 knockdown also inhibits the initial generation in mice of invasive ductal carcinomas and ductal carcinomas in situ from freshly isolated human mammary cells transduced, respectively, with KRASG12D or myristoylated-AKT1. Interestingly, increased expression of HIF1α and G3BP1, two YB-1 translational targets and elements of a stress-adaptive programme, mirrored the levels of YB-1 in both transformed primary and established MDA-MB-231 breast cancer cells.

Aberrant expression of E-cadherin in infiltrating ductal and lobular breast carcinomas and its correlation with clinicopathological parameters – A hospital-based study

Introduction: Breast carcinoma is one of the commonest malignant tumours in women, leading topremature deaths and morbidity. E-cadherin is a 120kDa calcium-dependent transmembraneglycoprotein encoded by the CDH1 gene located on chromosome 16q21 and is expressed in mostepithelial cells. Loss of E Cadherin expression implies cell discohesion and favours metastasis.Materials and Methods: A total of 30 cases of breast carcinomas were studied, over two years.Histological grade and type were assessed by staining the paraffin-embedded sections with H & E.Using IHC technique, E-cadherin antigen was retrieved by Heat-Induced Epitome Retrieval method,and immunostaining was scored semiquantitatively. Cases were grouped as ‘preserved,’ whenpositivity was strong membranous, and occurred in more than 75% of the neoplastic epithelial cellsand ‘aberrant’ in all the remaining cases. Results: E-cadherin was found to be preserved in 46.7%of all the breast carcinomas and aberrant in 51.7% of invasive ductal carcinomas (IDC) alone, while100% of invasive lobular carcinomas showed aberrant expression. No significant correlation wasfound with E-cadherin grading and histological type of carcinoma, histopathological grade orinvolvement of deep surgical margin. Conclusion: Differentiation between invasive ductal andinvasive lobular carcinoma based on the loss of E-cadherin has to be done cautiously given itsaberrant expression in ductal carcinomas as well.

Utility of Tissue Classification in Invasive Ductal Carcinoma using Dynamic Magnetic Resonance Imaging of the Mammary Gland

Objectives: In Japan, invasive ductal carcinomas, which account for 75% of breast cancer cases, are sub-classified as solid, tubule-forming, scirrhous, and other types based on the histopathological findings. Although time-intensity curve (TIC) analysis of magnetic resonance (MR) images has shown diagnostic ability in differentiating benign and malignant tumors, its ability to diagnose different tumor tissue types has not yet been achieved. In this study, we report a histological classification of invasive ductal carcinoma using the TIC analysis of dynamic MR images of the mammary gland. Material and Methods: A total of 312 invasive ductal carcinomas were analyzed, and each tissue type that indicated malignancy in the washout parts of the tumors was classified and characterized using the TIC. Results: The tissue was classified, and the results were then compared to the pathohistological diagnosis. Using this method, the accuracy of tissue classification by quantitative analysis of TIC-MR images was 86.9% (271/312), which was higher than that obtained by ultrasonography 68.9% (215/312). Conclusion: This method is effective for classifying tissue types in invasive ductal carcinoma.

The Receptor Tyrosine Kinase TrkA Is Increased and Targetable in HER2-Positive Breast Cancer

The tyrosine kinase receptor A (NTRK1/TrkA) is increasingly regarded as a therapeutic target in oncology. In breast cancer, TrkA contributes to metastasis but the clinicopathological significance remains unclear. In this study, TrkA expression was assessed via immunohistochemistry of 158 invasive ductal carcinomas (IDC), 158 invasive lobular carcinomas (ILC) and 50 ductal carcinomas in situ (DCIS). TrkA was expressed in cancer epithelial and myoepithelial cells, with higher levels of TrkA positively associated with IDC (39% of cases) (p < 0.0001). Interestingly, TrkA was significantly increased in tumours expressing the human epidermal growth factor receptor-2 (HER2), with expression in 49% of HER2-positive compared to 25% of HER2-negative tumours (p = 0.0027). A panel of breast cancer cells were used to confirm TrkA protein expression, demonstrating higher levels of TrkA (total and phosphorylated) in HER2-positive cell lines. Functional investigations using four different HER2-positive breast cancer cell lines indicated that the Trk tyrosine kinase inhibitor GNF-5837 reduced cell viability, through decreased phospho-TrkA (Tyr490) and downstream AKT (Ser473) activation, but did not display synergy with Herceptin. Overall, these data highlight a relationship between the tyrosine kinase receptors TrkA and HER2 and suggest the potential of TrkA as a novel or adjunct target for HER2-positive breast tumours.