Nancy Youssef Asaad

Immunohistochemical expression of GPR30 in breast carcinoma of Egyptian patients: an association with immunohistochemical subtypes

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.

Ephrin A4 expression in osteosarcoma, impact on prognosis, and patient outcome

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.

Pulmonary cryptosporidiosis: role of COX2 and NF-kB†

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.

The Prognostic Role of Ezrin and HER2/neu Expression in Osteosarcoma.

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.

The prognostic value of Skp2 expression in Egyptian diffuse large B-cell lymphoma.

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.

The Diagnostic Impact of C4d, Cd68, and Nf-κb Expression in the Differentiation Between Recurrent Hepatitis C and Acute Cellular Rejection After Liver Transplantation

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-&kgr;B) 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-&kgr;B 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-&kgr;B in the hepatocytes of recurrent hepatitis C could be an immune response to infection or it may be induced by HCV itself.

Immunohistochemical expression of topoisomerase II a and tissue inhibitor of metalloproteinases 1 in locally advanced breast 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.

Immunohistochemical profile of ephrin A4 expression in human osteosarcoma

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<0.05). The cytoplasmic pattern is the only staining pattern seen in metastatic cases, which may suggest its role in enhancement of invasion and metastasis. The differences in the distribution of the two patterns of ephrin A4 may indicate a different biological activity of this molecule depending on its localization. The nuclear localization of ephrin A4 requires further investigation to clarify the mechanism and the significance of the nuclear trafficking of ephrin A4.

Fine Needle Aspiration Cytology of Chondroid Tenosynovial Giant Cell Tumor of the Hand.

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.

The role of IL‐28, IFN‐γ, and TNF‐α in predicting response to pegylated interferon/ribavirin in chronic HCV patients

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.