Evaluation of Immunohistochemical Expression of ALK-1 in Gliomas, WHO Grade 4 and Its Correlation with IDH1-R132H Mutation Status.

BACKGROUND: Glioblastoma (GB), a grade 4 glioma is the most common primary malignant brain tumor in adults. Recently, the mutation status of isocitrate dehydrogenase (IDH) has been crucial in the treatment of GB. IDH mutant cases display a more favorable prognosis than IDH-wild type ones. The anaplastic lymphoma kinase (ALK) is expressed as a receptor tyrosine kinase in both the developing central and peripheral nervous systems. Increasing lines of evidence suggest that ALK is over-expressed in GB and represents a potential therapeutic target. OBJECTIVES: The goal of the current study was to investigate ALK-1 immunohistochemical expression in gliomas, grade 4, besides its correlation with IDH1-R132H mutation status and the clinicopathological parameters of the tumors. MATERIAL AND METHODS: Seventy cases of gliomas, grade 4 were tested for immunohistochemical expression of ALK-1 & IDH1-R132H in the tumor cells. RESULTS: ALK-1 immunoexpression was detected in 22.9% of our cases and IDH1-R132H mutation was detected in 12.9% of them. ALK-1 expression (100%) was only detected in the more aggressive IDH R132H-negative GBs. ALK-1 expression was also noted in the larger-sized tumors, more in males and patients older than the mean age.  Conclusion: Our results suggest that mutations in ALK-1 may predict a more dismal prognosis since ALK expression was only noted in IDH-R132H negative GBs known to have a considerably poorer outcome compared to IDH-R132H mutant cases. GBs with detectable ALK-protein expression could potentially experience substantial clinical advantages through the utilization of newly introduced ALK inhibitors allowing personalized treatment to a subset of patients. Hence, future studies targeting ALK in IDH wildtype Glioblastomas including clinical trials on larger scales are recommended.

Immunohistochemical Evaluation of Perlecan (Heparan Sulphate Proteoglycan 2) Expression in Invasive Female Breast Carcinoma.

BACKGROUND: Breast cancer (BC) is the commonest type of female cancer worldwide and a leading cause of cancer-related deaths. Perlecan expression increases in aggressive breast cancers, pointing to a possible significance of this novel target therapy. Consequently, the current research investigates the immunohistochemical expression of Perlecan by tumor cells in female breast cancer and the correlation of such expression with the pathologic parameters of the tumors. METHODS: A retrospective cross-sectional investigation was carried out. Seventy-four formalin-fixed, paraffin-embedded breast carcinoma tissue samples from patients undergoing modified radical mastectomy (MRM) or conservative breast surgery (CBS) were collected from the pathology department at Kasr El Aini Hospital. The paraffin blocks were sectioned and immunostained with Perlecan, and their expression was investigated in tumor cells and evaluated according to the H-score and classified into low and high expression. The expression was statistically correlated with the clinicopathological parameters of the cases. RESULTS: Perlecan expression was low in 41 cases (55.4%) and high in 33 cases (44.6%). It showed a statistically insignificant correlation with all studied parameters, but increased Perlecan expression was directly associated with poor tumor prognostic factors including higher tumor grade, advanced T stage, N3 stage, advanced anatomic stage, high Ki-67 index, positive lymphovascular invasion and perineural invasion, luminal B molecular subtype, and HER2 over-expression. CONCLUSION: Perlecan expression measured by immunohistochemical staining is associated with aggressive characteristics in breast cancer, suggesting that Perlecan may help in cancer progression and can be investigated as a possible target therapy.

Possible Role of IL-6R/STAT3/MiRNA-34a Feedback Loop in Osteosarcoma.

OBJECTIVE: Osteosarcoma is considered the most common primary malignant tumor that develops from the primary osteoblasts. MiRNAs are small non-coding RNAs that play a key role in tumorigenesis. The aim of this study was to detect the possible relationship between expression levels of miRNA-34a and levels of Signal transducer and activator of transcription 3 (STAT3) and interleukin-6 receptor (IL-6R) in osteosarcoma and the possible role of this relationship in development of metastases in these patients. METHODS: A total of thirty-six (36) bone samples were included in the study. They were divided into 3 groups: Group (I): Twelve normal bone samples as control group. Group (II): Twelve patients with non-metastatic osteosarcoma. Group (III): Twelve patients with metastatic osteosarcoma. MiRNA-34a expression levels were estimated using qRT-PCR. STAT3 and IL-6R levels were measured by ELISA. RESULTS: Expression level of miRNA-34a was downregulated in osteosarcoma groups compared to control group. STAT3 and IL-6R levels were upregulated in osteosarcoma groups compared to control group. This difference in expression levels was found to be more significant in the metastatic group than the non-metastatic one (P<0.001 each). There was a significant positive correlation between STAT3 and IL-6R (r=0.868, P<0.001), and a significant inverse correlation between IL6 and miRNA-34a (r=-0.993, P<0.001). CONCLUSION: miRNA-34a, STAT3 and IL-6R feedback loop could be a potential target for treatment of osteosarcoma and can be used as prognostic indicator for this disease.

Immunohistochemical Expression of Alpha-Methyl-Coa (AMACR) and ERG in Prostatic Adenocarcinoma and Prostatic Hyperplasia: A Comparative Study.

OBJECTIVE: This observational comparative study aimed at investigating the diagnostic accuracy of ERG in differentiating benign and malignant prostatic lesions and comparing it to the diagnostic accuracy of AMACR. We also aimed at comparing AMACR and ERG expression to Gleason grade of the carcinoma cases. METHODS: Seventy- two cases (22 prostatic hyperplasia and 50 prostatic carcinoma) were collected from the pathology department at Cairo university. The cases were immunostained by antibodies against AMACR and ERG. Immunohistochemical expressions of both markers were differentially examined in benign and malignant cases, compared to each other's, as well as, to the grade group of the malignant cases. RESULTS: AMACR showed 62% sensitivity and 86.4% specificity for the diagnosis of PC, with a statistically significant differential expression in benign and malignant lesions (P=0.001). Its expression also correlated significantly with the age (p=0.007), Gleason grade (P=0.006) and perineural invasion (P=0.011). Although ERG showed 100% specificity to PC with no expression in hyperplasia cases, it showed only 22% sensitivity for PC cases. ERG expression also showed statistically significant correlation with the Gleason grade. No association between ERG and AMACR expression was detected in our study (P=0.151). Regarding the diagnostic accuracy, although ERG accuracy was much lower than that of AMACR, combining both markers yielded a higher diagnostic accuracy. CONCLUSION: Although ERG proved no superior value than AMACR in diagnosing prostatic lesions, combining both markers may lead to higher diagnostic accuracy owing to higher ERG specificity for PC.