Loay M. Gertallah

Primary diffuse large B-cell non-Hodgkin's lymphoma of the breast—A case report and review of the literature

Primary breast lymphoma (PBL) is considered a rare clinical entity forming about 0.4%-0.5% of all breast tumors. In this report we have presented a case of PBL in a 56-year-old female complaining of a mass in the upper medial quadrant of the breast. PBL suspicion of our case was made by breast radiology and the sure diagnosis was reached by the immunohistochemistry results; CD (cluster of differentiation) 20: was diffusely positive; Pan-CK (pan-cytokeratin): was diffusely negative in tumor cells. Hence, the case was finally diagnosed as a primary breast a primary breast diffuse large B-cell non-Hodgkins lymphoma of lymphoma. The management and outcome of PBL and carcinoma are totally different. Accurate diagnosis of PBL by true cut needle biopsy and immunocytochemistry is important to avoid unnecessary mastectomies.

Simultaneous Repair of Para-Umbilical Hernia during Cesarean Section (CS): A Novel Approach

Background: Pregnant women that are complaining from paraumbilical hernia postpone its repair until they get birth. We hypothesized that it will be better to perform hernia repair of such type of hernia simultaneously during performing cesarean section (CS) which will help to decrease future morbidity re-operation, avoid complications and further skin incision. In this study we aimed to compare the value of performing para-umbilical hernia repair simultaneously during performing CS through the same skin incision with performing para-umbilical hernia repair simultaneously during performing CS through another infra- or supra-umbilical skin incision and performing para-umbilical hernia repair electively later on after healing of a CS skin incision in relation to clinical recovery and patient satisfaction. Patients and Methods: This is a prospective cohort study, where we included 45 pregnant female patients who will give birth by CS, and we have divided them into 3 groups: the first group of patients (A) included 15 patients that undergoing paraumbilical hernia repair by pre-peritoneal mesh insertion through CS incision, the second group of patients (B) in-cluded 15 patients that undergoing paraumbilical hernia repair by infra- or supra-umbilical incision during CS incision and the third group of patients (C) included 15 patients that undergoing paraumbilical hernia repair by infra- or supra-umbilical incision later on after healing of the CS wound. We have evaluated advantages of that novel approach e.g. operation time, severity of pain, peri-partum and post-operative complications, financial cost, duration of hospital stay, clinical recovery, mesh rejection, and patient satisfaction. Results: In group A there is shorter duration of hospital stay, no new skin incision (p 0.002). Conclusions: Performing para-umbilical hernia repair by insertion of a pre-peritoneal mesh simultaneously during performing CS through the same skin incision is the best method of management of para-umbilical hernia in pregnant woman.

SPOP, ZEB-1 and E-cadherin expression in clear cell renal cell carcinoma (cc-RCC): Clinicopathological and prognostic significance

BACKGROUND Clear cell renal cell carcinoma (cc-RCC), is a serious cancer regarding; its fatality, liability for metastases and chemoresistance, so identification of recent therapeutic targets to improve the patients prognosis is needed. SPOP is a BTB/POZ domain containing speckle-type POZ protein, has been identified as an E3 ubiquitin ligase component. ZEB1 is an essential epithelial mesenchymal transition (EMT) activator; E-cadherin is a cell adhesion protein that had been detected in normal epithelial cells membrane. AIM Was to assess the tissue protein markers SPOP, ZEB1 & E-cadherin expressions in benign areas of neoplastic kidney specimens and in cc-RCC patients, then correlating their expression levels with patients clinicopathological and prognostic data. METHODS We evaluated SPOP, ZEB-1 & E-cadherin expression using immunohistochemistry in samples from 50 cc-RCC and 20 benign areas of neoplastic kidney specimens, then we followed our patients for 5 years and finally we have analyzed correlations between the levels of markers expressions with patients clinicopathological and prognostic criteria in cc-RCC. RESULTS Positive expression of SPOP & ZEB1 in addition to negative E- cadherin expression was detected in cc-RCC more than benign areas of neoplastic kidney specimens (p = 0.004 and p < 0.001 respectively). In cc-RCC Positive expression of SPOP, ZEB1 and negative E- cadherin expression was associated with higher grade (p = 0.006, 0.007 & <0.001 respectively), advanced AJCC stage (p = 0.013, 0.023 & <0.001 respectively), presence of L.N metastases (p = 0.002 = 0.010 and <0.001 respectively), distant metastases (p = 0.001, 0.003 & 0.035 respectively), poor PFS and OS rates (p < 0.001 and p = 0.013 respectively). CONCLUSION Positive expression of SPOP& ZEB1 in addition to negative E- cadherin are associated with poor prognosis in cc-RCC patients.

The Value of FAK and SLUG Expression in Patients with Breast Carcinoma and Relation of Their Expression to Clinicopathological and Prognostic Parameters

Background: Although there is marked improvement in breast carcinoma (BC) management, it is still the leading cause of cancer death in middle-aged and old females, which leads to emergence of many studies about recent prognostic biomarkers that aimed to discover new therapeutic targets for BC. Focal adhesion kinase (FAK) is a member of protein tyrosine kinase (PTK) family. Slug is a member of the Snail family that is a C2H2-type zinc-finger transcription factor and plays an essential role in Epithelialmesenchymal transition [EMT] process activation in cancer. Our study aimed: To evaluate FAK and SLUG expressions in BC, to correlate their expressions with differentiation, invasiveness, metastatic potential of such type of cancer in addition to correlation with recurrence free and overall survival rates of female patients with breast cancer. Methods: We have assessed FAK and SLUG expressions in sections from 50 paraffin blocks of breast carcinoma using immunohistochemistry. We analysed correlations between their levels of expressions, clinic-pathological and prognostic criteria of our BC patients. Results: FAK and SLUG positive expression in breast carcinoma was related to positive expression in breast carcinoma was significantly correlated with aggressive molecular subtypes as HER2 amplified and triple negative subtypes, presence of lymph node metastases, high KI67 index, presence of distant metastasis (p<0.001 for all of them), negative ER & PR (p= 0.08), The expression of both markers was significantly positively correlated with each other (p<0.001). FAK and SLUG positive expression in breast carcinoma was associated with shortened recurrence free and overall survival rates (p<0.00). Conclusion: FAK and SLUG are markers of poor prognosis of breast carcinoma patients.

Prognostic and Clinicopathological Value of the Expression of FOXC2 & YKL-40 in Carcinoma of the Breast, an Immunohistochemical Study

Background: Breast cancer is considered the commonest and the most fatal female cancer worldwide. There is to an urgent need for discovering recent therapies to identify patient prognosis and improve treatment strategies. Fork-head Box C2 (FOXC2) is a transcription factor which is a key regulator of cancer stem cells (CSC) properties and epithelial mesenchymal transition (EMT) e.g. cancer initiation, metastatic capacity, and resistance to chemotherapy. FOXC2 roles in CSCs properties and EMT regulation in breast cancer needs detailed studies. YKL-40 is known as chitinase-3-like-1 belongs to a family of mammalian proteins that have an amino acid sequence which is similar to the 18-glycosyl hydrolase bacterial chitinases group. Recent studies have found aberrant YKL-40 elevated expression in cancer of various organs, so it may be used as a recent prognostic biomarker for patients with breast cancer. Former researchers have assessed the expression of FOXC2 & YKL-40 separately in cancer patients and relations to prognosis of patients; however, no studies assessed them together in breast cancer patients and the previous results were inconclusive. Accordingly, our study aimed at evaluation of immunohistochemical expressions of FOXC2 & YKL-40 in carcinoma of the breast in a trial to clarify the relation among their expressions, clinicopathological parameters and recurrence of the disease after successive therapy and patients’ prognosis. Methods: we have evaluated expressions of FOXC2 & YKL-40 in sections from 50 paraffin blocks of carcinoma of the breast using immunohistochemistry. We followed up our patients for 3 years for assessment of recurrence of the disease after successive therapy and survival rates. We analyzed the relationship between their combined expression clinicopathological and prognostic parameters. Results: high FOXC2 expression was associated with older age of the patient (p = 0.002), negative ER (p = 0.009), & PR (p = 0.008), positive HER2neu (p = 0.02), aggressive molecular subtype, higher grade of the tumor (p = 0.03), high incidence of distant metastasis (p = 0.011), high incidence of lymph node metastasis, higher KI labeling index, advanced stage, (p < 0.001). high YKL-40 expression was positively correlated with older age of the patient (p = 0.002), negative ER (p = 0.03), & PR (p = 0.04), positive HER2neu (p = 0.02), higher grade of the tumor (p = 0.003), high incidence of distant metastasis (p = 0.04), higher KI labeling index, aggressive molecular subtype, advanced stage, high incidence of lymph node metastasis (p < 0.001). We have found that patients with FOXC2 and YKL-40 overexpression have higher incidence of recurrence of the disease after therapy, poor RFS& OS rates (p < 0.001). Conclusion: Higher expression levels of FOXC2 & YKL-40 are markers of poor prognosis in breast cancer.

Panel of villin, pro-ex-c, estrogen receptor and progesterone receptor expressions could help in differentiation between endocervical and endometrioid adenocarcinoma

OBJECTIVE Endocervical and endometrioid adenocarcinoma have marked overlapping features and the differentiation between them is important for their accurate management. Villin is an actin-binding protein which has an important role in the maintenance of microvilli in epithelial cells and epithelial cell-specific anti-apoptotic protein processes. Pro-Ex-C is a marker for higher-risk human papilloma virus (HPV) which targets the cell cycle proteins causing their overexpression. The aim of the study was to clarify the diagnostic and predictive role of villin, Pro-Ex-C, estrogen receptor (ER) and progesterone receptor (PR) expression in endocervical and endometrioid adenocarcinoma. MATERIAL AND METHOD We evaluated villin, Pro-Ex-C, ER and PR expressions in 15 cases of endocervical adenocarcinoma and 30 cases of endometrioid adenocarcinoma. We analyzed the diagnostic and predictive role of that panel in both carcinoma subtypes. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. RESULTS Positive villin and Pro-Ex-C expressions were positively correlated with the presence and pattern of cervical stromal invasion (p < 0.05). ER was positive in all cases of endometrioid adenocarcinoma. PR was detected in most cases of endometrioid adenocarcinoma. The differences of villin, Pro-Ex-C, ER and PR expression in endocervical and endometrioid adenocarcinoma was statistically significant (p < 0.05). This methodology for distinguishing endocervical and endometrioid adenocarcinoma had a sensitivity of 100%, a specificity of 100% and a significant prognostic and predictive role. CONCLUSION In conclusion, villin, Pro-Ex-C, ER and PR expressions have diagnostic and predictive roles in endocervical and endometrioid adenocarcinoma.

The Value of HER2 neu and EphA2 expressions in Gastric Adenocarcinoma Prognosis

Background: Gastric adenocarcinoma (GAC) is a serious disease with poor outcome. Discovering novel molecular targeted therapies is a recent point of research to improve prognosis. One of the newly discovered targets is the receptor tyrosine kinases (RTKs); it is a member of trans-membrane receptors which had important roles in proliferation and apoptosis. RTKs were found to have different expression patterns in several malignancies. HER2 neu which is a member of HER family is a proto-oncogene that is formed of four receptor tyrosine kinases. Erythropoietinproducing hepatocellular (Eph) molecules are major RTKs members and one of those molecules is EphA2 which has many different functions in cancer as tumor initiation, progression, angiogenesis and spread. We aimed to explore the expression patterns of both HER2 neu and EphA2 in GAC patients using immunohistochemistry, and to correlate their expressions with clinico-pathological factors and prognosis of our patients Methods: HER2 neu and EphA2 expressions were assessed in sections from forty blocks of paraffin which were diagnosed as GAC. Then we analyzed the correlations between their expressions and disease outcome of GAC patients. Results: HER2 neu and EphA2 positive expressions in GAC were positively correlated with tumor grade and stage (p<0.001 and p=0.002 respectively), inadequate response to therapy (p<0.001 and p=0.002 respectively), increase recurrence rate of GAC (p=0.002), and with poor survival (p<0.001). Conclusion: GAC patients with high expressions of both HER2 neu and EphA2 had unfavorable prognosis.

Immunohistochemical expressions of SQSTM1/p62, Beclin-1, and SOX4 in infiltrating duct carcinoma of the breast

Background Breast cancer is the most common tumor and the second cause of death in women worldwide. Study of the molecular pathogenesis of breast cancer enables adequate management that will help to decrease its fatality. Autophagy is a lysosomal degradation process that removes damaged organelles to maintain cellular homeostasis. The role of autophagy in cancer is complicated; it may act as an inhibitor or a stimulator for cancer depending on the type of cancer. Thirty-four proteins have been detected in human cells and had 34 counterparts; yeast cells control this process. Beclin-1 is the human counterpart of the yeast Apg6/Vps30 gene; it plays an important role in autophagy. SQSTM1/p62 (Sequestosome-1) is an adapter protein that controlled the delivery of ubiquitin-bound cargo to the autophagosome. Epithelial–mesenchymal transition is the process by which epithelial cells alter their characteristics such as loss of cell–cell adhesion and downregulation of epithelial markers, followed by acquisition of mesenchymal characteristics such as increasing mobility, invasive power, and elevated resistance to apoptosis. The sex-determining region Y (SRY) box (SOX) family comprises 20 conserved transcription factors. SOX4, a member of the C subgroup of the SOX family, is characterized by an HMG box domain that binds the minor groove of the DNA helix. Aim of the work This study aimed to detect immunohistochemical expressions of SQSTM1/p62 and Beclin-1, comparing their expressions with each other and with SOX4 expression in infiltrating duct carcinoma of the breast to determine the relation between their expressions and prognosis of that type of cancer. Patients and methods Immunohistochemical expressions of SQSTM1/p62, Beclin-1, and SOX4 were evaluated in sections from 60 paraffin blocks of invasive ductal carcinoma (IDC) of the breast. The relationship between their level of expressions and prognosis of the patients was analyzed. Results The expression of SQSTM1/p62, in IDC was significantly positively correlated with size, grade, stage, local recurrence of the tumor, lymph node, and distant metastasis (P<0.001), the expression of Beclin-1 in IDC was significantly negatively correlated with size of the tumor, grade, stage, local recurrence, lymph node, and distant metastasis (P<0.001), and the expression of SOX4 in IDC was significantly positively correlated with stage, local recurrence, lymph node and distant metastases (P<0.001), and size and grade of the tumor (P=0.002). High SQSTM1/p62, SOX4 and low Beclin-1 expression were strongly correlated with worse 3-year overall survival (P<0.001) and local recurrence-free survival (P=0.007, 0.003, and 0.035, respectively). Conclusion High levels of expression of SQSTM1/p62 and SOX4 are markers of poor prognosis, whereas high levels of expression of Beclin-1 are a marker of good prognosis in IDC.