Relation Between Immunohistochemical Expression of Hippo Pathway Effectors and Chronic Hepatitis Induced Fibrosis in Egyptian Patients.

OBJECTIVE: Chronic hepatitis is a global health problem especially in Egypt. Hepatic fibrosis is a common end clinical manifestation of many chronic liver diseases. Although it is a wound-healing process, excessive accumulation of fibrillary collagen leads to architectural damage, cirrhosis and liver failure. Recently, a few studies have linked Hippo pathway effectors of yes-associated protein (YAP) and its paralog transcriptional coactivator with PDZ-binding motif (TAZ) to extracellular matrix deposition and ongoing fibrosis. MATERIAL AND METHOD: Immunohistochemical expression of YAP and TAZ were analyzed in 121 liver needle core biopsies (91 core biopsies of chronic viral hepatitis, 20 biopsies of autoimmune hepatitis and 10 normal liver cores). RESULTS: YAP and TAZ nuclear localization was absent in all normal liver cores. Autoimmune hepatitis cases showed higher nuclear expression of both YAP and TAZ in comparison to chronic viral cases. YAP and TAZ expression were correlated with severity of hepatocyte injury together with fibrosis in chronic viral cases but these correlations were absent in AIH cases despite the pronounced increase of YAP and TAZ nuclear localization. CONCLUSION: The correlation between Hippo effectors activation and fibrosis in chronic viral hepatitis patients emphasize their role in the development and advancement of hepatic scarring and highlight the use of both YAP and TAZ as novel targets to ameliorate liver fibrosis.

Immunohistochemical Expression of E- and N-Cadherin in Nodular Prostatic Hyperplasia and Prostatic Carcinoma.

BACKGROUND: Different theories have been postulated to explain the development of nodular prostatic hyperplasia (NPH). Epithelial to mesenchymal transition (EMT) is a physiologic process in which the epithelial cells lose their polarity and cell-cell adhesion and acquire a mesenchymal phenotype. AIM: The aim of the present study is to investigate the potential role of E- and N-cadherin in the induction of EMT in NPH and prostatic carcinoma. METHODS: This study was carried out on 55 cases of NPH and 20 cases prostatic carcinoma for evaluation of immunohistochemical expression of E and N cadherins. RESULTS: Most NPH (54/55 cases, 98.2%) and all cases of prostatic carcinoma showed positive N-cadherin expression in prostatic glands and stroma. High percentage of N-cadherin expression by stromal cells was significantly in favor of prostatic carcinoma compared to NPH. High percentage of N-cadherin expression by epithelial cells of carcinoma group was significantly associated with young age while its high expression by stromal cells was significantly associated with multicentricity. About 96.4% of NPH and 75% of prostatic carcinoma showed positive E-cadherin expression with a significant difference. No significant association between E-cadherin and N-cadherins in both NPH and prostatic carcinoma was identified. CONCLUSIONS: The prominent expression of N-cadherin in large numbers of NPH and prostate carcinoma cases in the epithelial and stromal components could point to the occurrence of EMT in those diseases. It also opens a new gate for treatment of those patients by targeting N-cadherin molecule. The absence of inverse association between E-cadherin and N-cadherins in NPH and prostatic carcinoma may indicate that cadherin switch is not an essential step for the development of EMT.

Human Epidermal Growth Factor Receptor-3 mRNA Expression as a Prognostic Marker for Invasive Duct Carcinoma not Otherwise Specified.

INTRODUCTION: Breast cancer is the most common cancer in women and the Erythroblastosis Oncogene B(ErbB) receptor family holds crucial role in its pathogenesis. Human Epidermal Growth Factor Receptor 3 (HER-3) gene over expression in breast tissue has been associated with aggressive clinical behaviour and bad prognosis. AIM: To evaluate HER-3 mRNA expression level as a prognostic marker for breast cancer and to correlate its level with other established prognostic parameters. MATERIALS AND METHODS: This study was carried out on specimens of 100 cases that were divided into 40 patients presented with fibroadenoma and 60 patients presented with Invasive Ductal Carcinoma (IDC) not otherwise specified and underwent modified radical mastectomy. All specimens were investigated for HER-2/neu, ER and PR expression by Immunohistochemistry (IHC) and quantitative assay of HER-3 mRNA expression using real time PCR technique. RESULTS: There was a significant high HER3 mRNA level in carcinoma cases compared to fibroadenoma. In malignant cases, HER3 mRNA level was significantly associated with advanced T stage, advanced N stage, number of positive lymph nodes, large tumour size and cases associated with an adjacent in situ component. Moreover, HER-3 mRNA level was of highest values in Her-2/neu positive group followed by triple negative cases with the lowest level in luminal group (p<0.05). CONCLUSION: HER-3 gene is upregulated in IDC especially those carrying poor prognostic features. HER-3 mRNA level may identify a subset of patients with a poor prognosis, and who could undergo further evaluation for the efficacy of HER3 targeted anticancer therapy.

Metastatic Collision Tumour (Papillary Thyroid Carcinoma and Squamous Cell Carcinoma) in Cervical Lymph Nodes: An Immunohistochemical Analysis.

Collision tumours are a rare entity, in this report, we describe a case of 73-year-old woman presented with a rapid enlargement of left upper cervical lymph node (LN) associated with right thyroid nodular goiter. The histopathological examination of the excised LN showed definite areas of papillary thyroid carcinoma admixed with moderately differentiated squamous cell carcinoma (SCC). Thyroglobulin immunostaining was positive in papillary carcinomatous areas confirming thyroid gland as a source of metastasis. Then the patient underwent total thyroidectomy and neck dissection, which revealed multicentric classic papillary thyroid carcinoma with an absence of squamous differentiation on extensive sampling. The patient received adjuvant radioactive iodine, but the neck swelling was rapidly progressing, ulcerated and infected. Computed tomography (CT) revealed left large cervical amalgamated LN and two metastatic lung nodules, the patient received 2 cycles of chemotherapy and was planned for external beam radiotherapy but she died within 7 months of first presentation. Collision tumours pose a diagnostic as well as therapeutic challenge and carry a rapidly progressive course and a fatal outcome. SCC is considered as a dedifferentiation of papillary thyroid carcinoma, which may appear in metastatic site rather than the primary site.

Primary Epithelioid Angiosarcoma of Spleen: A Case Report and Review of Literature.

Splenic angiosarcomas are usually secondary tumours, and only few primary cases have been encountered. We report a unique primary case of epithelioid angiosarcoma arising in the spleen in a male patient 55-year-old and presented to our hospital as a medical emergency with acute abdomen and haemorrhagic ascitis. CT revealed splenic focal lesion and suggested that this abdominal haemorrhage was due to ruptured splenic haemangioma, thus abdominal exploration and splenectomy were done. The histopathological examination showed an infiltrating ill-defined growth formed of high grade epithelioid cells arranged in sheet-like growth pattern, with occasional papillary appearance. The presence of rudimentary vascular channels lined by epithelioid endothelial cells with occasional intraluminal erythrocytes suggested vascular tumour origin. The neoplastic cells showed diffuse expression of CD31 together with focal expression of cytokeratin (CK) and CD34. Because of its epithelioid morphology and unmistakable positivity for CK, this case may be easily misdiagnosed as a metastatic carcinoma, which is not uncommon finding in the spleen. Epithelioid angiosarcoma is a rare type of vascular tumour in the spleen, which co-expresses vascular and epithelial markers making its distinction from metastatic carcinoma is sometimes difficult.