BackgroundThe diagnosis of uterine smooth muscle tumors depends on a combination of microscopic features. However, a small number of these tumors still pose difficult diagnostic challenges.AimTo investigate progesterone receptor (PR) and p53 expression in leiomyomas (LMs), atypical leiomyomas (ALMs), smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcomas (LMSs) and to evaluate the potential utility of the selected immunohistochemical markers in differentiating these tumors.Materials and methodsImmunohistochemical expression of PR and p53 was investigated in 41 uterine smooth muscle tumors comprising: 15 LMS, 4 STUMP, 6 ALM and 16 LM. Quantitative evaluation of PR and p53 expression was graded on a scale from 0 to 3+.ResultsLeiomyosarcomas showed reduced PR expression. All LMs as well as ALMs and STUMP were stained intensely for PR. Conversely, LMS was strongly stained with p53, while the three non-sarcomatous groups (STUMP, ALM, LM) were either entirely negative or weakly stained for p53. Regarding both PR and p53 expression, the difference between the LMS group and the three non-sarcomatous groups was highly significant (p < 0.001). Combined high PR - low p53 expression was seen in all the 26 examined cases of the non-sarcomatous group including the STUMP cases and none of the LMS cases. Therefore, it represents a "benign" profile with 100% specificity in diagnosis of a non-sarcomatous tumor.ConclusionImmunohistochemistry for PR and p53 is valuable as an adjunct tool to morphological assessment of problematic uterine smooth muscle tumors.

Combined utility of CD56 and claudin-1 is helpful in diagnosing the FVPC and its differentiation from other follicular patterned nodules. Application of these two markers may greatly aid in the reevaluation of the WDTs-UMP and interpretation of their expected behavior.

BackgroundThe microenvironment of astrocytomas includes infiltrative inflammatory cells that are dynamic in nature, possibly reflecting tumor biology. We evaluated the inflammatory cell infiltrate in astrocytic tumors aiming for a better understanding of their immunobiology.MethodsImmunohistochemical expression of CD68, CD3, and CD20 was investigated in 21 glioblastomas, 21 anaplastic astrocytomas, 13 diffuse astrocytomas, and 18 pilocytic astrocytomas. The inflammatory infiltrate was classified based on microanatomic location as perivascular and intratumoral, and subsequently graded semiquantitatively.ResultsPerivascularly, CD68-positive infiltrate was noted in 71.4% of glioblastomas compared with 14.3% of anaplastic astrocytomas (P = 0.0001), 7.7% of diffuse astrocytomas (P = 0.0001), and 33.3% of pilocytic astrocytomas (P = 0.017). Intratumorally, 85.7% of glioblastomas exhibited CD68-positive infiltrate compared with 42.9% of anaplastic astrocytomas (P = 0.004), 38.5% of diffuse astrocytomas (P = 0.008), and 33.3% of pilocytic astrocytomas (P = 0.001). Among diffusely infiltrating astrocytomas, intratumoral CD3-positive infiltrate was only associated with glioblastoma. A CD20-positive infiltrate was only detected in the perivascular space of a single case of diffuse astrocytoma.ConclusionThese data indicate a distinct immune profile in the glioblastoma microenvironment primarily related to the prevalence of macrophages. Thus, novel glioblastoma therapies should address this key CD68-positive population and its possible role in generating an antitumor immune response.

Background: The etiology of idiopathic granulomatous mastitis (IGM) is unknown, and it is commonly misdiagnosed clinically and/or radiologically as breast cancer. The role of fine-needle aspiration cytology (FNAC) in its diagnosis is still a matter of debate. The aim of the current study is to assess the value of FNAC in the diagnosis of IGM, and to search for the presence of bacteria in IGM with cystic vacuoles, which was described recently by a few authors. Materials and Methods: Retrospective study of cytologic smears and histologic tissue sections of 65 Egyptian IGM cases was done along with microbiologic testing. A comparison of the frequency of IGM in Egypt to that of other populations was also made. Results: IGM has typical FNA features which can easily exclude malignancy. Histologically, cystic vacuoles were encountered in 35 out of 65 cases (53.9%), with only 6 (17.14%) of these cases showing Gram-positive bacilli (GPB). The frequency of IGM in Egypt is comparable to those in other Middle Eastern countries but much higher than in Western countries. Conclusion: IGM is a common breast disease in Egypt. FNAC in IGM has a high diagnostic accuracy. This study supports the few recent studies that have detected GPB in IGM with cystic vacuoles. Thus, bacteriologic examination in such cases may affect the treatment strategy.

Doxorubicin (DOX) is one of the most potent and widely used chemotherapeutic agents to treat several malignancies. However, the clinical use of DOX is seriously restricted due to its acute and chronic cardiotoxic side effects This study investigated the protective effect of (Ajwa) date aqueous extract (AJDAE) against doxorubicin-induced cardiotoxicity in rats. Sixty Wister albino male rats (150-200 gms.) were comprised in our study and divided into six equal groups: group I (untreated control), group II, group III, rats were orally received AJDAE (0.75 & 1.5 gm/ kg.bw) respectively, for 4 weeks, rats of groups IV, V and VI were intraperitoneally injected with one dose of doxorubicin (5 mg/kg.bw) at the end of the 4th week of the study to induce cardiotoxicity, rats of groups V & VI were orally received AJDAE (0.75 & 1.5 gm/ kg.bw) respectively. Cardiac enzymes, lipid profile, SOD, GR, GST, GPx, CAT and MDA in rats’ hearts homogenate, urinary 8OHdG as well as DNA integrity and histopathological changes were investigated in all studied rats.Oral administration of AJDAE (0.75 & 1.5 gm/ kg.bw) attenuated the cardiotoxicity of DOX, improved the cardiac enzymes, lipid profile, reduced the urinary 8OHdG and prohibited the depletion of endogenous antioxidants and suppressed lipid peroxidation (MDA). Moreover, AJDAE enhanced DNA integrity. Histological findings showed that AJDAE (0.75 & 1.5 gm/ kg.bw) administration reduced cardiomyocytes alterations, congestion, edema and the intense cellular stress exerted on myocardial fibers as well as restored the cardiomyocytes architecture. Our data showed that AJDAE obviously resulted in protective effects against DOX-induced cardiotoxicity in rat’s heart. It can be concluded that Ajwa date offers a considerable protection against DOX-induced cardiotoxicity.

Toxoplasma gondii is an obligate intracellular protozoan that has a major importance in public health, in addition to veterinary medicine. Therefore, the development of an effective vaccine for controlling toxoplasmosis is an important goal. Excretory/secretory antigens (ESA), were previously identified as potential vaccine candidates, proved to play important roles in the pathogenesis and immune escape of the parasite. In addition, autoclaved Toxoplasma vaccine (ATV) is a special type of killed vaccine, recently characterized. The aim of the present work was, to compare between excretory/secretory and ATV against RH strain of T. gondii in mice based on; parasitological and histopathological levels. Tachyzoites were harvested from peritoneal exudates of infected mice and were used for challenge infection and vaccine preparation. BCG was used as an adjuvant. Mice were allocated equally into five groups; they were vaccinated intradermally over the sternum. The results of this study showed that the survival time after challenge, extended up to 16 days in ESA vaccinated group and up to 15 days in autoclaved Toxoplasma vaccinated group. ESA vaccinated group exhibited a profound decrease in parasite load following parasite challenge with a higher percentage of reduction in parasite count in all examined organs than the autoclaved Toxoplasma vaccinated group. The histopathological picture of the liver in both immunized groups, revealed marked reduction in the pathological changes observed as compared to controls, especially in ESA vaccinated group. It was concluded that vaccination with ESA showed more promising results versus ATV, as demonstrated by the survival rate of vaccinated mice, tachyzoites count and histopathological examination.

Cadherin switch (CS) outlined by downregulation of E-cadherin and upregulation of N-cadherin is an established epithelial-mesenchymal transition (EMT) hallmark, being a common signature in wound healing and carcinogenesis. It is intriguing to explore the EMT-associated CS pattern in precancerous phases as well as variably aggressive bladder cancer categories. In this study, we tested CS signified by a reduction in urothelial cells E-cadherin expression and/or aberrant N-cadherin expression in proliferative epithelial changes (PEC) associating inflammation, nonmuscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC). Immunohistochemical study of both E-cadherin and N-cadherin was performed for 60 cases: 15 PEC, 8 NMIBC, and 37 MIBC. CS patterns were analyzed: abnormal CS patterns were expressed as deviated, hybrid, co-negative, and full CS patterns. E-cadherin expression was significantly preserved in PEC (86.7%) followed by NMIBC (62.5%) and then MIBC (37.8%) (P = 0.004), whereas N-cadherin showed obvious aberrant expression in MIBC (51.4%) as compared with PEC (33.3%) and NMIBC (25%). In the MIBC group, abnormal cadherin patterns were the highest (70.3%) and was associated with adverse prognostic indicators. In the context of NMIBC progression to MIBC, combined E and N-cadherin evaluation showed highest sensitivity (70.3%) and NPV (31.3%), whereas aberrant expression of N-cadherin presented highest specificity (75%) and positive predictive value (90.5%). For cancer prediction, combined E-cadherin and N-cadherin evaluation showed the highest sensitivity (64.4%); abnormal E-cadherin offered highest specificity (86.7%), positive predictive value (92.9%), and negative predictive value (40.6%). In posttherapy follow-up setting, a metastable EMT signature in the form of partial CS was noted and might reflect resistant dormant populations.

Ovarian cancer is the most fatal gynecologic malignancy and the existing second-line treatments have not been confirmed to be effective. Cancer stem cells research has a leading role to explore promising therapeutic applications. Nestin was postulated to reflect cancer stem cell properties in various tumors, correlating with poor prognosis. Furthermore, nestin is proposed as a reliable neovascularization marker. This study aimed to elucidate the status of nestin expression in various epithelial ovarian cancers (EOCs), its neoangiogenic properties, and investigate its potential association with clinicopathologic parameters. A total of 80 primary EOCs (37 serous, 20 Mucinous, 13 endometrioid, and 10 clear cell carcinomas) were immunohistochemically stained with nestin. Staining intensity and automated microvascular density (MVD) were assessed. Positive nestin expression was defined in ≈47.5% of all EOC; more commonly in ≈60% of the serous tumors. It was noticeably expressed in tumor spheroids. Nestin expression significantly correlated with overall tumor grade, lymph node, distant metastasis, and stage. Nestin neoangiogenesis was detectable in all cases (average=60.1). The nestin expression in tumor cells significantly correlated with Nestin/MVD. The average Nestin/MVD was significantly an independent predictor of high tumor stage. As a stem cell marker, nestin is expressed in cells of EOC including those growing as spherules and correlated with poor prognosis. Thus, nestin may be a novel therapeutic target for tumor angiogenesis and a combination therapy that includes nestin-targeting agents may be an effective therapeutic approach. In addition, detection of Nestin/stem cells and Nestin/MVD can be used as predictors of disease.