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Introduction: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment. Methods: We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples. Results: Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival. Conclusion: Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.

Background: Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease. In addition, steatosis may lead to failure of obtaining sustained virological response after hepatitis C virus eradication. Therefore, there is a trend to identify effective strategies for managing hepatic steatosis. Farnesoid X receptor (FXR) agonists are reported to play a role in NAFLD treatment. Objective: This study aimed to explore the immunohistochemical expression of FXR in NAFLD spectrum in association with the clinicopathological data. Material and method: This was a retrospective study including 50 cases of NAFLD and 23 cases of normal liver. The NAFLD group was subdivided into 11 cases of NAFL (simple steatosis) and 39 cases of non-alcoholic steatohepatitis (NASH). Results: Hepatocyte FXR nuclear expression was significantly decreased in NASH group (P=0.001) with no significant decrease in NAFL group compared to normal liver (P=0.149). Bile duct FXR expression was significantly lower in NAFL group compared to normal liver (P= 0.009) to reach the lowest level in NASH group (P= 0.017). In NAFLD group, there was an inverse correlation between hepatocyte FXR nuclear expression and the ALT/AST ratio (r=-0.349 and P=0.013). However, hepatocyte FXR nuclear expression was significantly associated with moderate grade of steatosis and severe fibrosis (P= 0.044 and P= 0.033, respectively). Conclusion: Hepatocyte FXR nuclear expression showed a stepwise decrease in its expression from normal to NASH passing with NAFL. Therefore, FXR has a protective role against NAFLD progression. Elevated liver enzymes could be used as a non-invasive method for monitoring FXR agonists' efficacy.

Molecular subtyping of urothelial carcinoma (UC) is similar to that of breast cancer and is based on the developmental biology approach. The aim of the present study is to assess the prognostic impact of CK5, CK14, and CK20 expression in urinary bladder cancer (UBC) with the potential to stratify them into different subtypes. The current study examined the immunohistochemical expression of CK5, CK14, and CK20 in 90 specimens of UBC. CK5 was expressed in 81.1% of the cases and was significantly associated with old age, muscle invasion, presence of bilharziasis, and tendency for poor overall survival. CK20 was expressed in 47.8% of the cases and was associated with nonmuscle invasion and pure UC while 50% of the cases expressed CK14 that were associated with muscle invasion and perineural invasion. Most squamous cell carcinoma and those associated with bilharziasis were belonged to Ck5+/CK20- subgroup while pure UC and those lacked bilharziasis were located in the Ck5+/CK20+ subgroup. The basal group (Ck5+/CK14+/CK20-) showed high proliferative features compared to the intermediate group (Ck5+/CK14-/CK20-). Generally, presence of CK5 is associated with adverse features especially in the group lacking CK20; however, basal and intermediate subgroups share CK5 expression but they show different proliferative capacities, so their distinction by CK14 is helpful.

ObjectivesTo evaluate the role of the epithelial–mesenchymal transition (EMT) profile, Twist, E-cadherin, and vimentin in the progression of colorectal carcinoma (CRC).BackgroundMetastases are the most common cause of death in cancer patients. EMT is one of the central mechanisms that induces invasi

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in Egypt and worldwide. Gene expression profiling classifies DLBCL into: germinal center B cell-like (GCB) and non germinal center B cell-like (non-GCB) DLBCL. Hans' algorithm has high concordance with gene expression profiling results. Regulatory T cells (Tregs) represent important modulators for the interaction between lymphoma cells and host microenvironment. FOXP3 is a popular single marker for Tregs. There is little information about the possible role of Tregs in high-grade lymphoma such as DLBCL. This study aims to assess the prognostic impact of FOXP3+ Tregs in DLBCL. The study was carried out on 70 archival cases (61 de novo DLBCL and 9 reactive follicular hyperplasia cases). DLBCL cases were classified into GCB and non-GCB groups using Hans' algorithm. All studied cases are subjected to FOXP3 immunostaining. Density of FOXP3+ Tregs was higher in reactive cases compared with DLBCL (P=0.000). In DLBCL cases, FOXP3 expression was associated with free spleen (P=0.02), early stage (P=0.05), centroblastic variant (P=0.003), and absence of necrosis (P=0.05). In germinal cases, density of FOXP3 was significantly higher in cases with good PS (P=0.02), very good and good revised international prognostic index (P=0.002), and low-risk age-adjusted international prognostic index >60 (P=0.01). Non germinal DLBCL cases with negative FOXP3 were significantly associated with splenic involvement (P=0.005). DLBCL cases with high FOXP3 have longer survival (P=0.03). T cells in the background of DLBCL may play a role in modulation of tumor progression. Their presence is associated with favorable prognostic parameters in DLBCL.

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.

Liver transplantation is the selected treatment for patients with advanced liver disease and cirrhosis, mostly as a complication of hepatitis C virus (HCV). Recurrent HCV and acute cellular rejection (ACR) of the graft are the most common causes of graft failure. The distinction between the 2 conditions is essential because they are managed differently. In some cases, the clinical and histopathologic features may overlap between recurrent hepatitis C and ACR, making differentiation difficult. The aim of this study was to investigate the role of C4d, CD68, and nuclear factor kappa-B (NF-κB) in the differentiation between ACR and recurrent HCV in the post-liver-transplant biopsy using immunohistochemistry. C4d expression in endothelial cells of portal or central veins (P=0.001) and the number of macrophages highlighted by CD68 (P=0.02) were in favor of ACR, whereas NF-κB expression by hepatocytes was in favor of recurrent hepatitis C. Vascular injury demonstrated by endothelial expression of C4d and prominent macrophage infiltration identified by CD68 expression were the distinguishing criteria for ACR and representing humoral and cellular-mediated immunity as evoking factors for graft injury. The upregulation of NF-κB in the hepatocytes of recurrent hepatitis C could be an immune response to infection or it may be induced by HCV itself.

Osteosarcoma is the most common primary malignant bone tumor in Egypt. Ezrin is involved in cell adhesion to the extracellular matrix and in cell-cell interactions facilitating metastasis. HER2/neu is overexpressed in breast cancer and other types of cancer. This study aimed to assess the expression of ezrin and HER2/neu in 57 primary osteosarcoma cases and to correlate their expression with the available clinicopathologic parameters and the overall, metastasis-free and event-free survival. Both ezrin and HER2/neu were not expressed in the normal bone and they were upregulated in 82.5% and 71.9% of osteosarcoma, respectively. Positive ezrin expression was significantly associated with young age (below 25 y) (P=0.01), high grade (P=0.001), and short survival time (P=0.0001). Positive HER2/neu expression was significantly associated with high-grade osteosarcoma (P=0.04). Membranous HER2/neu expression was the only factor that showed significant impact on metastasis-free (P=0.002) and event-free survival (P=0.002). Ezrin was significantly correlated with HER2/neu expression (P=0.02). Advanced stage (P=0.0001), metastasis (P=0.0001), and recurrence (P=0.01) were the factors affecting the overall survival of osteosarcoma patients. Ezrin and HER2/neu are overexpressed and coexpressed in osteosarcoma with adverse prognostic features such as high grade. Membranous pattern of HER2/neu seems to be more important than the cytoplasmic pattern because of its impact on metastasis-free and event-free survival. Therefore, ezrin and HER2/neu could be potential prognostic markers and treatment targets for osteosarcoma.

Purpose: Locally advanced breast cancer (LABC) is a heterogeneous entity that remains a clinical challenge. Anthracycline-based neoadjuvant chemotherapy has emerged as the standard of care for those patients. However, it is associated with serious side effects including cardiotoxicity. This study aimed to evaluate the prognostic and predictive role of topoisomerase IIα (TOP2α) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in Egyptian LABC patients after anthracycline-based neoadjuvant chemotherapy. Materials and Methods: This retrospective study was conducted on 84 LABC cases. Immunohistochemical expression of TOP2α and TIMP-1 was evaluated in pretreatment needle core biopsies. Results were correlated with clinicopathlogic parameters, response to neoadjuvant chemotherapy in postoperative specimens, disease-free survival and overall survival (OS). Results: Positive TOP2α expression was detected in 57/84 (67.9%) cases. It was significantly associated with good response to chemotherapy in breast (P=0.048) and lymph node (P=0.06) as well as prolonged OS (P=0.04). It tended to be the most independent prognostic factor for OS (P=0.06). Positive TIMP-1 expression was detected in 48/84 (57.1%) cases. It was significantly associated with poor response to chemotherapy in breast (P=0.02). The 2T profile (TOP2α+ and TIMP-1−) was significantly associated with good response to chemotherapy in breast (P=0.006). Conclusion: TOP2α and TIMP-1 are important predictive and prognostic factors in LABC patients who received anthracycline-based chemotherapy.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a separate entity by the World Health Organization in 2017 with strict inclusion and exclusion criteria. Most NIFTP cases have been reported in adults and few cases have been diagnosed in children. Here, we present a classic case of NIFTP affecting a 10-year old female child. We also review previous reports of NIFTP in children regarding size, focality, nodal metastasis, recurrence, type of operation and follow-up data. The present report adds a new case of NIFTP in the paediatric age group characterized by multifocality, absence of nodal invasion and indolent course until last follow-up, recommending less aggressive management.

Background and study aim: The association between H. pylori infection and cirrhosis in patients with hepatitis C virus has been documented in different parts of the world. Eradication treatment may prove beneficial in those patients with chronic hepatitis C. The aim of the present study was to study H. pylori infection in patients with portal hypertensive gastropathy. Patients and Methods: This study was conducted on Session [CurrentTestPartID] patients; 45 patients with portal hypertensive gastropathy (Group A). In addition to 15 patients with chronic gastritis without portal hypertension (Group B). All patients were subjected to full history tacking and complete physical examination. Routine laboratory investigation including, CBC, PT, PC, INR, SGOT, SGPT, S. Albumin, S. Bilirubin. Radiological examination including abdominal ultrasound, and Doppler study for Portal vein. Upper GIT endoscopy, and biopsies from the antrum. Histopathological examination of the biopsies for assessment of congestive gastropathy and H. pylori infestation if present. Results: This study demonstrated that the Session [CurrentTestPartID]% of patients of group A and 66% of patients of group B have H. pylori infection. There was no predilection for H. pylori infections in patients with PHG than those in patients with gastritis. In group A, 53% of patients with varices had H. pylori infection while 47% did not have H. pylori infection. Also, 76% of the non H. pylori patients had esophageal varices while Session [UserIDID]% of patients with non H. pylori subgroup had no varices. Additionally, patients of group A with mild PHG and H pylori constituted 26.5%, those with moderate PHG and H pylori constituted 47% while patients with severe PHG and H pylori constituted 26.5%. Conclusion: This study demonstrated that there is no predilection concerning the presence of H pylori infection in patients with PHG and there is no relation between the degree of PHG and the presence of H pylori infection.

Objective : Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous group of tumors with different biological and clinical characteristics that have diverse clinical outcomes and response to therapy. Stromal-1 signature of tumor microenvironment of DLBCL represents extracellular matrix deposition and histiocytic infiltrate, whereas stromal-2 represents angiogenesis that could affect tumor progression.Methods : The aim of the present study is to assess the significance of stromal-1 signature using SPARC-1 and stromal-2 signature using CD31 expression and then finally to construct biologic prognostic model (BPM) in 60 cases of DLBCL via immunohistochemistry.Results : Microvessel density (PPP=0.008), high mitotic count (P=0.045), and presence of capsular invasion (P=0.035). Percentage of SPARC expression was significantly associated with splenic involvement (P=0.03). Constructing BPM showed that 42 cases (70%) were of low biologic score (0–1) and 18 cases (30%) were of high biologic score (2–3). Low BPM cases showed less probability for splenic involvement (P=0.04) and a higher rate of complete response to therapy compared with high score cases (P=0.08).Conclusions : The DLBCL microenvironment could modulate tumor progression behavior since angiogenesis and SPARC positive stromal cells promote dissemination by association with spleen involvement and capsular invasion. Biologic prognostic models, including modified BPM, which considered cell origin of DLBCL and stromal signature pathways, could determine DLBCL progression and response to therapy.

The primary goal of HCV therapy is to achieve a sustained virological response (SVR). Many host and viral factors influence the treatment response. Cytokines play an important role in the defense against viral infections, where successful treatment of hepatitis C depends on a complex balance between pro- and anti-inflammatory responses. In the present study, we investigated the relationship between the presence and percentage of some cytokines (IL-28, IFN-γ, and TNF-α) regarding different clinicopathological parameters including response to therapy in chronic HCV patients using immunohistochemical technique. This study was carried out on 64 chronic HCV patients (34 responders and 30 non-responders). Of cases, 54% showed IL-28 expression, which was associated with low AST (p = 0.002) and low HAI score (p = 0.006). Of cases, 67 and 45% showed IFN-γ and TNF-α expression, respectively, where the median percentage of TNF-α expression was higher in grade II spotty necrosis compared to grade I. Some inflammatory cytokines expressed by intrahepatic inflammatory cells in chronic HCV patients promote inflammation and injury (pro-inflammatory) such as TNF-α. Other cytokines aid in resolving inflammation and injury (anti-inflammatory) such as IL-28. The balance between these cytokines will determine the degree of inflammatory state. None of the investigated cytokines proved its clear cut role in affecting response to therapy, however, their levels varied between responders and non-responders for further investigations to clarify.

Surface epithelial tumors of the ovary are no longer considered as a single disease but are divided into types I and II on the basis of their molecular features, cell of origin, and their behavior. A possible direct action of gonadal steroids on ovarian carcinogenesis has been suggested. The current information about the possible role of TFF1 in ovarian tumors,, together with its relationship to the estrogen receptor (ER) status, is insufficient. The aim of this study was to investigate ERα, ERβ, and TFF1 expression in type I and II ovarian tumors and their correlation with clinicopathologic parameters of each type. The present study was carried out on 97 ovarian tumors [20 benign, 15 borderline, and 62 malignant (36 type I and 26 type II tumors)]. ERα expression was significantly in favor of type II tumors (P=0.04), whereas high TFF1 expression was significantly in favor of type I tumors (P=0.02). ERα and ERβ showed a significant positive correlation in benign cases (P=0.004) and in type I tumors (P=0.006), but not in type II tumors. In type I tumors, the expression of ERα was correlated with serous carcinoma (P=0.002) and bilaterality (P=0.05), whereas TFF1 was correlated with mucinous carcinoma (P=0.02), unilaterality (P=0.04), early FIGO staging (P=0.01), and a low mitotic count (P=0.03). A high ERβ:ERα H score ratio was associated with advanced FIGO staging in both type I (P=0.05) and type II tumors (P=0.009). The difference in the expression of ERα and TFF1 between type I and II tumors may be indicative of the difference in their origin and molecular pathway. The ERβ:ERα ratio is more important in determining the net result of ER effects than the evaluation of each receptor separately, and the high ratio may promote progression to advanced stage in type I and II ovarian tumors. High TFF1 expression in ovarian mucinous carcinoma may indicate that their mucinous differentiation is toward an intestinal type rather than an endocervical type. TFF1 expression in ovarian tumors seems to occur independent of the status of the ER.

The high incidence and mortality of lung carcinoma in Egypt necessitates studying the factors that may be implicated in non-small cell lung carcinoma (NSCLC) pathogenesis and could affect patient management. The aim was to study FHIT, epidermal growth factor receptor (EGFR), and MSH2 protein expression in Egyptian patients with NSCLC. Immunohistochemical staining for FHIT, EGFR, and MSH2 was performed on 64 specimens from NSCLC patients and correlated with prognostic parameters, response to therapy, and overall survival. FHIT loss was observed in 64% of NSCLC patients and was significantly associated with SCC (P=0.003) and poor tumor grade (P=0.043). EGFR overexpression was observed in 47% of NSCLC patients and was significantly associated with SCC (P=0.002). MSH2 was reduced in 23.4% of NSCLC patients and was significantly associated with adenocarcinoma (P=0.024). In a univariate analysis, a significant relationship was seen between the poor overall survival in NSCLC patients and high T-stage (P=0.029), presence of metastasis (P=0.014), advanced-stage grouping (P=0.004), and FHIT loss (P=0.033). Further, FHIT loss was significantly related to disease progression in patients treated with chemotherapy (P=0.038). We conclude that all 3 markers play a role in the development of NSCLC in Egyptian patients. We suggest that FHIT loss be used as a predictor for progression in chemotherapy-treated NSCLC patients.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma worldwide. Both morphologically and prognostically, it represents a disease of a diverse spectrum. S-phase kinase-associated protein 2 (Skp2) is a member of mammalian F-box proteins, which displays S-phase-promoting function through ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor, p27. The aim of this study is to evaluate the prognostic value of Skp2 in DLBCL (70 cases) by immunohistochemical staining technique, and its correlation with the clinicopathological features and survival. Five (25%) control cases (reactive follicular hyperplasia) showed high Skp2 expression compared with 52.9% of DLBCL using 10% as a cutoff point with a significant difference (P=0.04). Skp2 was seen staining the large cells in proliferating germinal centers of the control group. High Skp2 expression in DLBCL was associated with several progressive parameters, such as advanced stage (P=0.036), involvement of more than one extranodal site (P=0.05), and high proliferation (P=0.0001). It was also significantly associated with the presence (P=0.007) and extent (P=0.002) of necrosis and inversely correlated with p27 expression (P=0.0001). From this study, Skp2 expression in DLBCL identified subset of cases characterized by aggressive features such as advanced stage, increased number of extranodal sites, high proliferation, and shorter survival time. The association of Skp2 with necrosis may be a reflection of its ability in promoting proliferative tumor capacity.

In this report, we describe a classic case of stroma rich neuroblastoma, nodular type in a 22 year old female presented with a pancreatic mass. This rare and unusual presentation elicits several differential diagnostic categories including solid pseudopapillary tumor, pancreatic endocrine tumor, pancreatoblastoma and PNET. In this report, we tried to differentiate between them depending on the histopathological features and using panel of epithelial and neuroendocrine markers. Although of the rarity of pancreatic neuroblastoma as a primary site of origin, however it should be considered in the differential diagnosis of pancreatic masses in children and young adult. Neuropil and ganglionic differentiation are helpful features to recognize neuroblastoma and differentiate them from other small blue cell tumors. The fatal outcome of adult neuroblastoma confirming the independence of age as a prognostic factor in this neoplasm regardless of stage and histology.

Objectives The aim of this study was to assess the impact of neoadjuvant chemoradiation on the pathologic response and survival of patients with rectal cancer. Background Colorectal cancer is one of the most common human malignancies; there are a number of potential advantages for using neoadjuvant chemoradiation. They include the ability to deliver higher doses of chemotherapy with radiation, downstage the tumor, which has been noted in 60–80% of patients, and to achieve a pathologic complete response, which occurs in 15–30% of patients. The ability to ‘shrink’ the tumor facilitates surgical resection and performs a sphincter-preserving operation, radiating tissues with a greater oxygen supply, and decreases the likelihood of developing radiation enteritis, because the small bowel is less likely to enter the pelvis. Patients and methods This study included 80 patients with operable cancer rectum. A total of 40 randomized patients were treated with neoadjuvant chemoradiotherapy (CRT) followed by surgery, and the other 40 patients underwent surgery without neoadjuvant CRT. The pathological response to neoadjuvant CRT with regard to tumor necrosis, size, negative margins, number and size of lymph nodes with operative findings with regard to resectability and blood loss were assessed and then the follow-up of patients was carried out and compared with another group. Results We detected a statistically significant difference between both groups with regard to some pathological responses, including grade of tumor differentiation, number and positivity of lymph nodes, perioperative complication, and disease-free survival but no difference in overall survival. Conclusion Neoadjuvant chemoradiation could affect the disease-free survival of patients with rectal carcinoma.

Follicular dendritic cell sarcoma (FDCS) is a rare malignant tumor that could arise in both nodal and extranodal sites, with only nine previously reported cases demonstrating cytologic features. In this report, we describe a case of FDCS in a 60-year-old female who presented with neck mass. Fine-needle aspiration cytology and subsequent core biopsy were suggestive of metastatic carcinoma. The cytologic features were epithelioid-to-spindle cell morphology, vesicular nuclei, prominent nucleoli, intranuclear inclusions, and occasional binucleated and multinucleated forms. However, absence of cytokeratin expression was against the diagnosis of metastatic carcinoma. The definitive diagnosis was reached by the demonstration of CD21 and CD23 expression. The pathologist should be aware of this rare malignant tumor, especially its cytologic features in aspirated material. The differential diagnosis in the above case was metastatic carcinoma, melanoma, and malignant granular cell tumor. The demonstration of expression of one or more dendritic cell marker is the clue for the diagnosis, which could be applied on cytological preparations with sufficient material.

Dermatofibroma is a common cutaneous benign fibrohistiocytic tumour, which is usually diagnosed without difficulty. In this report we demonstrated a signet ring variant of dermatofibroma as a rare variant of this common neoplasm together with the possible differential diagnosis.The presence of signet cells in cutaneous neoplasm does not necessarily means malignancy. Signet ring dermatofibroma is a rare variant eliciting differential diagnostic problems which can be solved by careful histopathological examination, searching for the classic areas and the help of immunohistochemistry.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphomas worldwide. The pathogenesis of lymphomas is not yet well understood. SV40 induces malignant transformation by the large T-antigen (L-TAG) and promotes transformation by binding and inactivating p53 and pRb. L-TAG can bind pRb promoting the activation of the E2F1 transcription factor, thus inducing the expression of genes required for the entry to the S phase and leading to cell transformation. This immunohistochemical study was conducted to assess the prognostic role and relationship of SV40 L-TAG and E2F1 in diffuse large B-cell lymphoma (DLBCL) of Egyptian patients. This retrospective study was conducted on 105 tissue specimens including 20 follicular hyperplasia and 85 DLBCL cases. SV40 L-TAG was identified in 3/85 (4%) of DLBCL. High Ki-67 labeling index (Ki-67 LI) and apoptotic count were associated with high E2F1 expression (pfor all). No significant association was reached between E2F1 and SV40. E2F1 expression proved to be the most and first independent prognostic factor on overall survival of DLBCL patients (HR = 5.79, 95% CI = 2.3–14.6, andp). Upregulation of E2F1 has been implicated in oncogenesis, prognosis, and prediction of therapeutic response but is not seemingly to have a relationship with the accused SV40.

In the present study we investigated whether the pathological changes induced by Cryptosporidium in the lungs are mediated through the activation of COX-2, and whether the pathway employed for this activation involves NF-kB. 70 albino rats were submitted for this work. They were categorized into 3 groups: 30 immunocompetent (IC) rats infected with Cryptosporidium oocysts, 30 immunosuppressed (IS) rats infected with Cryptosporidium oocysts, and 10 IC, non-infected rats. Immunohistochemical expression of COX2 and NF-kB in lung tissues of the rats was examined. 43.3% of IC rats showed chronic pneumonia and fibrosis, 40% COX2 positivity, and 36.67% NF-kB positivity. 96.7% of IS rats showed chronic pneumonia and fibrosis, 56.7% non-caseating granuloma with Cryptosporidium oocysts, and 66.7% positivity for both COX2 and NF-kB. Density of inflammatory infiltration was statistically correlated with quickscore of both COX2 and NF-kB in both IC and IS groups. An association between quickscores of COX2 and NF-kB was found in our studied material. These data could demonstrate that Cryptosporidium infection induces upregulation of COX2 possibly through the NF-kB pathway, which suggests the events that contribute to the pathogenesis of Cryptosporidium. These findings could indicate potential therapeutic pharmacological target-mediating treatment of lesions caused by Cryptosporidium.

Aims : To determine the prevalence of Epstein–Barr virus (EBV) infection in primary extranodal lymphoma of the head and neck (PELHN) in immunocompetent patients. PELHN represents 16.18% of all lymphoma diagnosed at the National Cancer Institute, Cairo. Although EBV infection is highly associated with lymphoma in immunocompromised patients, the situation in immunocompetent patients is still unclear. Material and methods : The study included 50 PELHN (11 cases in the nose and paranasal sinuses, 11 in the nasopharynx, 13 in the tonsils, seven in the oropharynx and eight in the oral cavity), five reactive lymph nodes, 15 normal nasopharyngeal tissue and 25 throat washes of healthy subjects from Egypt. Cases and controls were assessed for the presence of EBV by polymerase chain reaction (PCR) and in situ hybridization techniques, the presence of 30 base pair deletion of the LMP-1 (del-LMP1) gene and for the expression of p53, Ki67, bcl-2 and Bax by immunohistochemistry. This was also correlated with the clinical outcome of patients. Results : EBV was detected in 90% and 70% of the cases using EBER in situ hybridization and PCR, respectively. All cases of nasal type lymphoma were positive for EBV. del-LMP1 gene was detected in 24/35 of EBV+ cases (68.6%), whereas 11 cases had wild-type variant either alone or mixed with del-LMP1. There was a significant difference in the frequency of del-LMP1 between lymphoma and normal tissues. Overexpression of Ki67, p53 and bcl-2 was detected in 78.1%, 62.5% and 20% of cases, whereas loss of Bax was detected in 18% of the cases. Multivariate analysis showed that only p53 overexpression, del-LMP1 variant and advanced disease stage are independent prognostic factors. Conclusion : EBV infection is frequent in PELHN in Egypt. Possible pathogenic mechanisms involve deregulation of p53 and enhanced proliferation (as detected by high Ki67 index). The presence of del-LMP1 variants, p53 overexpression and advanced disease stage are poor prognostic factors associated with reduced survival and poor response to therapy.

Objectives The aim of this study was to explore the relationship between immunohistochemical expression of Twist and the relevant clinicopathological features of colorectal carcinoma (CRC) in Egyptian patients. Background In Egypt, there is an increasing incidence of CRC, especially among patients of 40 years of age or less. Worldwide, many efforts have been made to find biomarkers to predict the behavior of CRC. Epithelial-mesenchymal transition is one of the central mechanisms that induces invasion and metastasis of tumors. Twist has been shown to induce epithelial-mesenchymal transition and play a critical role in cancer metastasis. In addition, Twist proteins display oncogenic properties by preventing senescence and apoptosis. Materials and methods Using the standard immunohistochemical technique, we assessed Twist expression in 67 colorectal specimens, including 10 specimens from normal colonic mucosa, eight colonic adenoma, and 49 CRC cases, and correlated our results with the available clinicopathological parameters. Results Negative Twist cytoplasmic immunoreactivity was detected in all the normal colonic mucosa specimens, whereas 75% of adenomas and 85.7% of CRC showed positive Twist cytoplasmic expression. Negative Twist nuclear immunoreactivity was detected in all the normal colonic mucosa and adenoma specimens, whereas 44.9% of CRC showed positive nuclear Twist expression. Nucleocytoplasmic Twist expression was significantly associated with high-grade tumors, mucinous adenocarcinoma, and advanced Dukes' stage, and showed a high tendency to be associated with vascular invasion. Conclusion The negativity of Twist in normal colonic mucosa confirm Twist as an embryonic transcription factor that remains largely undetectable in healthy adult tissues and involved in oncogenesis and malignant transformation in CRC. Being negative in adenoma and expressed only in CRC, Twist nuclear translocation may be a late event in carcinogenesis. Nucleocytoplasmic Twist expression is associated with poor prognostic factors in CRC.

Sebaceous trichofolliculoma is considered as hamartomatous lesion with follicular differentiation. In this study, we demonstrated a classic histopathologic picture of sebaceous trichofolliculoma in a 65-year-old male presented with large sized right cheek swelling.

Tumor-associated macrophages (TAMs) and dendritic cells (DCs) may play a role in tumor progression as a part of the tumor microenvironment in many neoplasms, including those in Hodgkin's lymphoma. The current study investigated the relationship between the presence and density of macrophages and dendritic cells in the background of classic Hodgkin's lymphoma (CHL) and different clinicopathological parameters, including survival and response to therapy. CD68 and CD1a immunohistochemical staining were used to detect and highlight macrophages and dendritic cells, respectively, in 61 cases of CHL. CD68 was expressed in all studied cases, with no significant association with the studied parameters. In total, 54.1% (33/61) of cases showed CD1a expression. High CD1a expression (>7%) was associated with localized lymphadenopathy (p=0.01), early stage (p=0.005), and good revised international prognostic index (R-IPI) (p=0.07). Hodgkin's lymphoma cases that showed high CD68 and low CD1a were associated with adverse prognostic parameters such as advanced stage (p=0.03) and generalized lymphadenopathy (p=0.05). Old age (>60 years) (P=0.005), poor R-IPI (P=0.010), and negative CD1a expression (P=0.045) were significantly associated with poor outcome. Finally, our study demonstrated the importance of the presence and density of DCs in determining progression and prognosis in CHL. A certain interaction between TAMs and DCs may affect the progression of CHL. Further investigation is required to clarify whether TAMs release certain factors that decrease the number or function of DCs.

Giant cell tumor (GCT) of tendon sheath is a localized form of tenosynovial GCT, which preferentially affects the joints of hands and feet. Chondroid metaplasia is a rare phenomenon in tenosynovial GCT either in localized or diffuse types. The current case investigates the cytological and histopathological features of chondroid GCT of tendon sheath in a 22-year-old female presenting with wrist swelling.

Breast carcinoma in Egyptian women is a biologically more aggressive disease than those diagnosed in Western women, although a substantial number of cases are hormone responsive. G protein-coupled receptor-30 (GPR30), a seven transmembrane domain protein, is currently recognized as an estrogen receptor. This study aimed at evaluating the expression of GPR30 in breast carcinomas of Egyptian patients and its association with clinicopathologic parameters and immunohistochemical subtypes of breast carcinoma. Immunohistochemical staining for GPR30 was applied on 51 archival formalin-fixed paraffin-embedded cases of invasive ductal carcinoma. Staining was assessed using a semiquantitative scoring system taking staining intensity and extent into consideration. GPR30 was observed in 33/51 (65%) of invasive ductal carcinoma cases. GPR30 was significantly associated with larger tumor size (p = 0.009), increased number of positive lymph nodes (p = 0.04), definite lymph-vascular invasion (LVI) (p = 0.002), peri-nodal invasion (p = 0.02), and the presence of coagulative tumor cell necrosis (p = 0.02). Moreover, a significant association between positive GPR30 expression and ER positivity (p = 0.02), as well as HER2/neu positivity (p = 0.03), were also observed. Most of the luminal A and B subtypes were GPR30 positive; however, all the triple negative cases were GPR30 negative (p = 0.010). GPR30 might contribute to the aggressive behavior of Egyptian breast carcinoma. Therefore, it could be useful in the therapeutic decision making in breast cancer patients.

Objectives The aim of this work was to study the immunohistochemical expression of CD44 in colorectal carcinoma (CRC) cases. Background Cancer stem cells (CSCs) have a role in cancer initiation, progression, and metastasis of CRC through their ability of self-renewal and unlimited proliferation, and they seem to be responsible for local relapse and metastasis. Several markers for CSCs have been investigated in CRC, and CD44 was the most likely marker for colorectal CSCs. Materials and methods This retrospective study included 71 colorectal specimens (49 CRC, 13 adenoma, and nine normal cases). The studied cases were collected from the Pathology Department, Faculty of Medicine, Menoufia University, during the period from 2011 to 2015. All cases were stained with CD44 antibody. Survival data were available for 31 of 49 studied CRC cases. Results All cases of normal colonic epithelium and normal colon adjacent to CRC showed no membranous CD44 immunoreactivity; 84.6% of the studied adenoma cases showed no expression of CD44, whereas 57.1% of CRC cases showed positive expression. There was a statistically significant association between positive epithelial expression of CD44 and left-sided tumors (P = 0.01). There was a statistically significant difference between CRC and colorectal adenoma (P = 0.007) and between CRC and normal cases (P = 0.000) as regards CD44 expression. There was a highly statistically significant association between stromal expression of CD44 and absence of lymph node invasion (P = 0.002) as well as early Dukes' stage (P = 0.01). Conclusion CD44 may be involved in the pathogenesis of CRC. Stromal expression only of CD44 is associated with better prognostic factors.

Background : Ephrin A4 is one of the ephrin ligand molecules belonging to the tyrosine kinases receptor family. It was originally identified in a T-lymphoma cell line and seen to be expressed in human adult tissue as well as several tumor types. In our previous study, we showed the unique pattern of ephrin A4 immunohistochemical staining, which differed according to the type of examined bone specimens (normal bone, primary, and metastatic osteosarcoma lesions). The aim of the present study is to evaluate the prognostic impact of ephrin A4 expression in a group of primary osteosarcoma patients. Materials and Methods : Ephrin A4 immunohistochemical expression was carried out on 47 primary osteosarcoma cases. Results : Ephrin A4 was expressed in 82.9% of osteosarcoma cases with cytoplasmic localization in 58.9% of positive cases. The cytoplasmic pattern was significantly associated with aggressive histopathological types of osteosarcoma (P = 0.02), advanced stage (P = 0.04), the presence of metastasis (P = 0.03), inferior response to neoadjuvent chemotherapy (P = 0.04), and tended to be associated with a shorter event-free survival (P = 0.09). Conclusions : The cytoplasmic pattern of ephrin A4 could identify a subgroup of primary osteosarcoma patients with a high liability for progression, poor prognosis, and inferior response to chemotherapy.

Galectin-3 is a human lectin linked to malignant transformation in different organs including thyroid gland. We aimed to evaluate the diagnostic role of galectin-3 in differentiating benign from malignant thyroid lesions in cytological and histological samples.This study included a total of 79 cases; 19 multinodular goiter (MNG), 19 follicular adenoma (FA), 13 follicular carcinoma (FTC) and 28 papillary carcinoma (PTC). Galectin-3 immunostaining was applied on histological sections from all the cases (retrospective analysis) as well as for the available preoperative FNAC (28 cases) (prospective analysis).Retrospective analysis: The positivity percentage of galectin-3 was 10.5%, 92.3%, 93% for nonmalignant, FTC and PTC respectively. According to H score, glaectin-3 immunostaining was significantly lowered in FA) 1+/-2.8 as compared to papillary (158.5+/-88.6) and follicular carcinoma (150+/-83.9) (p0.0001). However, there was no statistically significant difference between FTC and PTC (p=0.56) or between classic and follicular variants of PTC (p=0.51). Sensitivity, specificity, positive and negative predictive values for galectin-3 staining were 93%, 89.5%, 90.5% and 92% respectively. Prospective analysis: There were five benign, six malignant and 17 indeterminate cytology cases. Galectin-3 immunostaining was able to detect the benign nature of 11/17 indeterminate cytology. Combination of standard cytological evaluation with galectin-3 immunostaining markedly improved sensitivity (71% versus 85%), specificity (75% versus 94%), positive predictive value (83% versus 92%) negative predictive value (60% versus 87.5%) and diagnostic accuracy (72% versus 90%).We suggest Galectin-3 as a supplementary immunostaining in histological diagnosis of difficult thyroid follicular lesions and in preoperative evaluation of indeterminate thyroid cytology to avoid unnecessary aggressive surgical interference in benign lesions.

Ephrin receptors and ephrin ligands constitute one of the largest groups of tyrosine kinases. The division of ephrin receptors into type A or type B is determined by their ligand-binding specificities. Ephrin A4 as a ligand has a broad capacity to bind and stimulate different subtypes of ephrin A receptors. Little is known about the role of ephrins generally and ephrin A4 particularly in osteosarcoma. Ephrin A4 was immunohistochemically assessed on archival material from 46 primary osteosarcoma cases, 10 metastatic pulmonary lesions and 20 normal control bone specimens. Ephrin A4 was expressed in 100% of normal bone specimens, in 84.4% of primary osteosarcoma cases and in all metastatic pulmonary lesions. Cytoplasmic and nucleocytoplasmic patterns of ephrin A4 immunoreactivity were observed, with the predominance of the latter pattern in normal bone (100%), and in 43.5% of primary osteosarcoma cases, which showed a higher intensity of expression compared with normal bone (p

HCV-associated hepatocellular carcinoma (HCC) is a common neoplasm in Egypt where genotype-4 is prevalent. In the present study the incidence and pattern of p53 mutations was assessed in relation to HCV-genotype- 4 in Egyptian HCC patients. We investigated 25 HCV positive HCCs for p53 mutations/overexpression in relation to HCV-NS3 by immunohistochemistry, SSCP and sequencing. Genotyping was done using LiPA-II and TRUGENE 5' NC' sequencing kit. Results were correlated to standard clinicopathologic prognostic factors for HCC. Thirteen cases showed p53 overexpression, and 10 showed p53 mutation (13 mutations) by sequencing (72% concordance). The highest mutation rate was in exons 6 and 7 (30%) followed by exons 5 and 8 (20%). Mutations included 3 transitions, 5 transversions, 3 deletions, and 2 insertions. All exon 7 mutations were at codon 249 specific for AFB1 (AGG--AGT, Arg--Ser) and codon 248 specific for vinyl chloride contamination (CGG--TGG, Arg--Trp). Other mutations reported are novel. Immunostaining for HCV NS3 was detected in 19 cases independent of p53 mutation. p53 aberrations were significantly associated with poor prognostic factors for HCC. However, no specific pattern for p53 mutations was observed in HCV genotype 4-associated HCC and no significant relation between p53 mutations, HCV-NS3 expressions or any HCV sub-genotype-4 sequence.

The catalytic component of telomerase, human telomerase reverse transcriptase (hTERT) has been found to be reactivated in immortalized cell lines and considered as a diagnostic marker for malignancy in different body tissues.Therefore we thought to determine whether hTERT gene detection could serve as an adjunct in the diagnosis of thyroid lesions together with evaluation of its prognostic value.The study included 50 cases of primary thyroid carcinoma including; 28 papillary carcinoma, 14 follicular carcinoma, 5 anaplastic carcinoma and 3 medullary carcinoma in addition to 5 cases of nodular hyperplasia and 5 cases of follicular adenoma. RNA was extracted from paraffin sections of those patients and hTERT gene expression was identified by Reverse Transcription-Polymerase Chain Reaction (RT-PCR).RT-PCR of hTERT gene revealed expression in 43/50 (86%) malignant thyroid cases; including 25 papillary, 11 follicular, 4 anaplastic and 3 medullary carcinoma cases. On the other hand, hTERT gene expression could not be detected in either hyperplastic nodule or in follicular adenoma cases. The diagnostic validity of hTERT gene detection in benign and malignant thyroid lesions was in the form of 88.3% accuracy, 86% sensitivity, 100% specificity, 100% positive predictive value and 90% negative predictive value. No significant association has been found between hTERT gene expression and any clinicopathologic parameters concerned in this study. In thyroid carcinoma cases, hTERT gene detection was the most independent predictor of poor survival by multivariate survival analysis.Detection of hTERT gene expression should be considered in confirmation of malignant thyroid lesions. Moreover it could be one of the helpful tools in addition to grade, tumor type, and age to stratify patients with thyroid carcinoma into different prognostic categories. Hence, inhibition of hTERT could be of use prospectively in the era of cancer therapy as an attractive weapon in thyroid carcinoma.

Objectives To evaluate immunohistochemical expression of topoisomerase II a (TOP2α) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in an attempt to identify their prognostic roles in locally advanced breast cancer (LABC). Background LABC is a heterogeneous clinical entity that remains a clinical challenge. Efforts are still needed to identify new markers in an attempt to predict response to therapy and prognosis. Patients and methods This study included 84 pretreatment needle core biopsies of LABC cases subjected to TOP2α and TIMP-1 immunohistochemical staining and the expression was correlated with some prognostic clinicopathlogical parameters of the patients studied. Results Fifty-seven of 84 cases (67.9%) showed positive TOP2 expression, with the proportion of TOP2α immunopositive cells (%score) ranging from 0 to 95%, mean ± SD of 27.84 ± 26.16%, and the median was 25%. Positive TOP2α expression was significantly associated with the presence of necrosis ( P = 0.03). There was also a near-significant association between positive TOP2α expression and high mitotic count ( P = 0.08). Forty-eight of 84 cases (57.1%) showed positive TIMP-1 expression with proportion of TIMP-1 immunopositive cells (%score) ranged from 0 to 95%, mean ± SD of 35.59 ± 32.93%, and the median was 30%. Positive TIMP-1 expression was significantly associated with a low apoptotic count ( P = 0.03). Conclusion TOP2α-positive expression in diagnostic samples of LABC patients is associated with poor prognostic features such as the presence of necrosis, whereas TIMP-1 is associated with a low apoptotic count.