Androgen receptor expression in triple negative breast carcinoma and its association with the clinicopathological parameters

@#Introduction: Androgen receptor (AR) is the most frequently expressed biomarker in all subtypes of breast carcinoma. Triple negative breast carcinoma (TNBC) is breast carcinoma that lacks oestrogen and progesterone receptors immunoexpression as well as absence of HER2/neu gene amplification. This makes targeted therapy not feasible in this cancer and hence has poorer prognosis. Detecting AR expression could be another milestone in the management of TNBC, as AR is a prognostic, predictive marker and potential index for targeted treatment. This study aimed to assess expression of AR in TNBC by immunohistochemistry and its association with clinicopathological parameters. Methods: We analysed the expression of AR in 97 TNBC cases from Penang General Hospital for a period of 3 years (2014 to 2017). Androgen receptor immunoreactivity was considered positive if > 1% of tumour cells nuclei were stained irrespective of staining intensity. Results: The prevalence of AR expression in TNBC was 31% (30/97), with the proportion of AR-positive tumour cells ranged from 1% to 90%. These include 23 invasive carcinomas, no special type (NST) and 7 other invasive carcinoma subtypes (papillary, lobular, clear cell and medullary carcinomas). Sixty-seven cases (69%) that showed AR immunonegativity were invasive carcinomas, NST (n=60), clear cell carcinoma (n=1) and metaplastic carcinoma (n=6). Androgen receptor immunoexpression was inversely correlated with tumour grade (p=0.016), but not the tumour stage, tumour size and nodal status. Conclusion: AR is expressed in about one-third of TNBC and loss of AR immunoexpression does not predict adverse clinical outcomes. Larger cohorts for better characterisation of the role of AR immunoexpression in TNBC are warranted.

Vascular Endothelial Growth Factor Expression in Renal Cell Carcinoma

@#Introduction: Renal cell carcinoma (RCC) is the most common renal malignancies. In advanced stage, it is highly resistant to systemic therapies. RCC is a highly vascular tumour and angiogenesis pathway has been postulated in its carcinogenesis. Novel drug targeting Vascular Endothelial Growth Factor (VEGF) and advanced surgical interventions have shown to increase the overall patients’ survival. In this study, we evaluated the VEGF expression of RCC using immunohistochemistry technique and its potential correlation with the tumour grades. Methods: 40 RCC cases that underwent nephrectomy were selected. The archived samples of formalin fixed, paraffin-embedded (FFPE) were retrieved. The tumour tissue blocks were carefully chosen, sectioned and stained with VEGF using immunohistochemistry technique. The intensity of VEGF expression was scored as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong). Results: Majority of the RCC cases were male, with male to female ratio of 2.1:1. Mean patient age was 56.2 years (age ranged between 16 to 74 years). Most of the cases were Malays (42.5 %). VEGF was expressed in 36 (90%) of RCC cases. Among the 36 cases that were immunopositive, 8 (16.7%) were grade 1, 20 (55.6%) grade 2 and 8 (16.7%) grade 3. There was no significant association between VEGF expressions score and grades of RCC (p=0.39). Conclusion: VEGF was expressed in majority of RCC cases although there was no significant association with tumour grades.

Determinants of lymph node status in women with breast cancer: A hospital based study from eastern India.

Background & objectives: Number of metastatic lymph nodes has a strong prognostic value in the course of breast cancer treatment, morbidity and mortality. This study was undertaken to determine the association between axillary lymph node metastasis and several variables such as age, tumour size, grade, lymphovascular invasion, oestrogen and progesterone receptor expression and HER2/neu status in patients with breast cancer. Methods: In this study 426 (with complete information on study variables) patients with breast cancer on treatment during March 2010 to December 2013, were analyzed. TNM (tumour node matastasis) staging was evaluated. The histological grading of tumours was done according to modified Bloom-Richardson Grading System. The immunophenotype of the tumour was determined as the expression of oestrogen (ER) and progesterone (PR) receptors and HER2/neu status. Univariate and multivariate analyses were carried out to determine the independent predictors of metastatic lymph node. Results: Among the studied patients, 44.36 per cent (189 of 426) of the patients had nodal metastases. Tumour histology, tumour grade, size and lympho-vascular invasion were related with node positivity. On univariate analysis, age, menopause, hormone receptor status did not relate with the node metastasis. Age, tumour grade, tumour size, lympho-vascular invasion and HER2/neu expression was likely to be associated with the number of lymph node metastasis. Interpretation & conclusions: The lymph node status was associated with clinical stage, tumour grade, tumour histology and HER2/neu status. These factors may be used for better management of such patients.

E-cadherin downregulation at the infiltrating tumour front is associated with histological grade and stage in colorectal carcinoma of Malaysians

Loss of E-cadherin, a 120 kDA transmembrane glycoprotein responsible for cell-cell adhesion, is one of the hallmarks of epithelial-mesenchymal-transition (EMT). E-cadherin expression was immunohistochemically studied in 94 histopathologically re-confirmed colorectal carcinomas (CRC) using a monoclonal antibody to E-cadherin (Dako: Clone NCH-38) on a Ventana Benchmark XT automated system. Each case was assessed for E-cadherin immunopositivity at two separate locations viz the tumour centre (TC) as well as the infiltrating front (IF). Expression was semiquantitated for proportion of immunopositive malignant cells as 0 (negative), 1 (1-25% staining), 2 (26-50% staining), 3 (51-75% staining) and 4 (>75% staining) and staining intensity: 0 (negative), 1 (weak), 2 (moderate) and 3 (strong). The final histoscore of E-cadherin immunopositivity was arbitrarily computed as proportion of immunopositivity multiplied by staining intensity of the malignant cells. E-cadherin histoscores were significantly lower at the IF (4.5 ± 2.5) compared with TC (10.7 ± 2.4). Furthermore, the histoscores were significantly reduced at the IF of 49 TNM III+IV tumours (3.6 ± 2.5) compared with 45 II+III CRC (5.4 ± 2.2). Reduction of E-cadherin expression was also noted in the 23 high grade (TC=8.6 ± 3.2; IF=2.6 ± 2.3) compared with 71 low grade tumours (TC = 11.4 ± 1.5; IF = 5.1 ± 2.3). E-cadherin is downregulated at the infiltrating front of CRC, possibly marking for EMT at this location. The downregulation is further enhanced amongst late stage and high grade tumours compared with earlier stage and low grade tumours; findings which are similar to that noted in CRC of other populations.