Saleh, M. M., T. M. Abdelrahman, Y. M. Said, G. Mohamed, A. M. Shokry, and A. F. Moustafa, "Multi-parametric MRI with Diffusion-Weighted imaging in predicting response to chemotherapy in cases of osteosarcoma and Ewing's sarcoma.", The British journal of radiology, pp. 20200257, 2020. Abstract

OBJECTIVE: To evaluate the multi-parametric MRI in predicting chemotherapy response in pathologically proven cases of osteosarcoma and Ewing's sarcoma. Correlation between the tumor size changes and internal breakdown using RECIST 1.1, modified RECIST, quantitative ADC and tumor volume as well as dynamic contrast enhanced MRI.

METHODS: The study included 104 patients pathologically proved osteosarcoma (53) and Ewing`s sarcoma (51) underwent MRI examinations; beforeand after chemotherapy. All patients were assessed using the RECIST 1.1 criteria, m-RECIST, quantitative ADC, and tumor volume evaluation. 21 patients underwent DCE-MRI curve type with quantitative parameters. Correlation between the different evaluations was carried out. Results were correlated with the postoperative pathology in 42 patients who underwent surgery and for statistical evaluation, Those patients were classified into responders (≥90% necrosis) and non-responders (<90% necrosis).

RESULTS: The initial mean ADC of 104 patients of osteosarcoma and Ewing's sarcoma (0.90 ± 0.29) and (0.71 ± 0.16) respectively, differed significantly from that after treatment (1.62 ± 0.46) and (1.6 ± 0.39) respectively with (P<0.001).ADC variations (ADC%) in the non-progressive group were higher than those of the progressive group (128.3 ± 63.49 vs 36.34 ± 78.7) % with (P<0.001).ADC values and ADC variations were inversely correlated with morphologic changes, regardless of the effectiveness of chemotherapy expressed as changes in tumor size based on (RECIST 1.1, RECIST, and 3D volume). Linear regression analysis revealed a Pearson correlation coefficient of r=(-0.427, -0.498 and -0.408), respectively with (P<0.001).An increase in the ADC value was not always associated with a reduction in tumor volume. The disease control rate (defined as the percentage of CR+PR+SD patients) was 89.4% and 93.9% according to RECIST 1.1 and m-RECIST respectively.42 out of the 104 patients had postsurgical histological evaluation as regards the chemotherapeutic response divided into two groups. ADC values showed a statistically significant difference between Group A and Group B being more evident with minimum ADC% (P<0.001).

CONCLUSION: Quantitative DW imaging with ADC mapping and ADC % after chemotherapy allows a detailed analysis of the treatment response in osteosarcoma and Ewing's sarcoma. The therapeutic response can be underestimated using RECIST 1.1, so the modified RECIST should be also considered.

ADVANCES IN KNOWLEDGE: Quantitative ADC especially ADC% provided an accurate non-invasive tool in the assessment of post-therapeutic cases of osteosarcoma and Ewing's sarcoma.

Ismail, A., G. Mohamed, M. F. Amer, and F. A. L. - Z. Mohamed, "Association of SNPs in miR-196a2 with the risk of Ovarian Cancer and its relation with Clinicopathological data", Cancer Biology, vol. 8, issue 3, pp. 31-37, 2018.
Mohamed, G., I. L. Abulkheir, and M. Mourad, "FOXP3-positive regulatory T cells are correlated with improved survival in diffuse large B-cell non-Hodgkin lymphoma", Egyptian Journal of Pathology, vol. 37, issue 1, pp. 104-111, 2017.
Gad, M., A. Abou-Bakr, R. A. S. H. A. M. A. H. M. O. U. D. ALLAM, H. R. Nassar, M. H. Ibraheem, S. Talima, and G. Mohamed, "Significance of PD-L1 Expression and Tumor Infiltrating Lymphocytes in High Grade Serous Ovarian Cancer: Egyptian Experience", Indian Journal of Public health research and develeopment, vol. 11, issue 1, pp. 1718-1724, 2020.
Ibraheem, M. H., M. Ali, A. Hafez, G. Mohamed, R. Boutros, O. Talaat, and M. Gamil, "The Relationship Between Positive Sentinel Lymph Node Biopsy and Residual Axillary Lymph Nodes Status in Early Stage Breast Cancer", Journal of Cancer Science and Clinical Therapeutics, vol. 4, issue 1, pp. 1-14, 2020.
Atef, N., N. Alieldin, G. Sherif, I. Loay, A. Mostafa Mahmoud, and G. Mohamed, "Microsatellite Instability and Life Style Factors in Sporadic Colorectal Cancer.", Asian Pacific journal of cancer prevention : APJCP, vol. 21, issue 5, pp. 1471-1480, 2020. Abstract

BACKGROUND: Colorectal cancer (CRC) in Egypt is a relatively high young onset disease. As a form of heterogeneous cancer, there is interplay between genetic and environmental factors. We aimed at probing the association of life style factors and Microsatellite Instability (MSI) status that could provide more insights on carcinogenic process of CRC.

METHODS: One hundred incident sporadic CRC patients were involved. Information on risk factors of CRC was obtained and microsatellite instability status was predicted through evaluation of MMR protein expression via immunohistochemistry (IHC).

RESULTS: Median age was 47.50 years, females represented 54.0% and 36% of patients were Microsatellite Instability High (MSI-H). Most patients with right sided colon cancer (78.3%) were MSI-H while mostly stable or low MSS/MSI-L for left-sided colon and rectum (78.6%, 74.3% respectively, p<0.001). Patients with low physical activity had higher risk of MSS/MSI-L than those with moderate or high activity p =0.026. Patients with BMI greater than 30 Kg/m2 had higher MSS/MSI-L (75.5%) than those with BMI between 25-30 Kg/m2 (60.6%) and those with normal BMI.

Ismail, A., R. El-Awady, G. Mohamed, M. Hussein, and S. S. Ramadan, "Prognostic Significance of Serum Vitamin D Levels in Egyptian Females with Breast Cancer", Asian Pacific journal of cancer prevention : APJCP, vol. 19, issue 2, pp. 571-576, 2018. Abstract

Objective: To determine the frequency and prognostic significance of vitamin D deficiency in Egyptian women
with breast cancer (BC). Methods: This prospective study included 50 women with primary invasive, non-metastatic
BC. The serum level of 25-hydroxy vitamin D [25(OH)D was measured by ELISA at diagnosis, before any cancer
treatment. Vitamin D deficiency was defined as 25(OH) D<20 ng/mL. Patients were followed up for a median of 30
months (range: 18-48). Results: The median level of 25(OH)D was 29.0 ng/mL (range: 10.0-55.0 ng/mL). Fifteen
patients (30%) had vitamin D deficiency, which was positively associated with larger tumor size (p < 0.001), higher
grade (p = 0.014), advanced stage (p = 0.001), lymph node positivity (p = 0.012), and HER2/neureceptor expression
(p = 0.002). It was also linked with worse overall survival (OS) and disease free survival (DFS) (p = 0.026, and
p = 0.004, respectively). On multivariate analysis, DFS was independently affected by vitamin D deficiency with
an HR of 2.8 (95% CI: 1.6-7.0, p = 0.022) and advanced stage, i.e. stage II had worse survival compared to stage I with
an HR of 4.8 (95%CI: 1.1-21.7, p = 0.042). Conclusion: Vitamin D deficiency had a negative effect on overall and
disease-free survival in our breast cancer cases, being related to tumor size, stage, grade, nodal status and HER2/neu
receptor expression.

El-Bolkainy, T., G. Mohamed, and O. Badawy, "Precursor Lesions of the Vocal Cord: a Study on the Diagnostic Role of Histomorphology, Histometry and Ki-67 Proliferation.", Pathology oncology research : POR, vol. 26, issue 1, pp. 515-520, 2020. Abstract

The precise typing of precursor lesions of squamous cell carcinoma of vocal cord is of vital importance since it determines the line of therapy and prognosis. The aim of the present study is to evaluate the possible value of the types of dyskeratosis, histometry and cell proliferation rate in discriminating these lesions. The present retrospective study was based on 145 patients, classified according to the updated 2017 WHO system and included: Low-grade dysplasia (24 cases), high -grade dysplasia (53 cases), carcinoma insitu (33 cases) and microinvasive carcinomas (35 cases). Cell proliferation was assessed by immunoreactivity to Ki-67. For histometry and quantitation of Ki-67 proliferation rate, an image analysis system was used (Leica LAS, Wetzlar, Germany). Epithelial pearls (cell nests) were commonly observed in microinvasive carcinoma (82.9%) than high-grade dysplasia (5.9%). The median epithelial thickness, as well as, proliferation rate showed a significant increase according to the grade of the lesion. It is concluded that dyskeratosis pattern, histometry and Ki-67proliferation rate are valuable parameters to characterize precursor lesions. The presence of epithelial pearls, thickness > 450 μm and Ki-67 > 40% denote high risk lesions that require adequate excision and/or radiotherapy.

Mohamed, G., S. Talima, L. Li, W. Wei, Z. Rudzki, R. A. S. H. A. M. A. H. M. O. U. D. ALLAM, W. Simmons, Q. Tao, and P. G. Murray, "Low Expression and Promoter Hypermethylation of the Tumour Suppressor SLIT2, are Associated with Adverse Patient Outcomes in Diffuse Large B Cell Lymphoma.", Pathology oncology research : POR, vol. 25, issue 3, pp. 1223-1231, 2019. Abstract

SLIT2 has been classified as a major tumour suppressor gene due to its frequent inactivation in different cancer types. However, alterations of SLIT2 expression and relation to patient outcomes in diffuse large B cell lymphoma (DLBCL) remain undefined. The aim of this study was to investigate the expression and the methylation status of SLIT2 gene as well as its relation to patient outcomes in DLBCL. Immunohistochemical (IHC) staining was carried out to detect the expression of SLIT2 in a series of 108 DLBCL cases. Re-analysis of previously published dataset (GSE10846) that measured gene expression in DLBCL patients who had received CHOP or R-CHOP therapy was performed to identify associations between SLIT2 and patients survival. Laser capture microdissection was performed to isolate GC B cells and DLBCL primary tumor cells. Bisulfite treatment and methylation-specific PCR (MSP) analysis were done to assess SLIT2 promotor methylation status. We report that the expression of SLIT2 protein was reduced in a subset of DLBCL cases and this was significantly correlated with advanced clinical stage (p = 0.041) and was an independent predictor of worse overall survival (OS) (p = 0.012). Re-analysis of published gene expression data showed that reduced SLIT2 mRNA expression was significantly correlated with worse OS in R-CHOP-treated ABC DLBCL patients (p = <0.01). Hypermethylation of the SLIT2 promotor was significantly correlated with low SLIT2 expression (p = 0.009). Our results provide a novel evidence of reduced expression of SLIT2 that is associated with promoter hypermethylation and adverse outcomes in patients with DLBCL.

Mohamed, G., P. Murray, E. Nagy, and K. Vrzalikova, "Epstein–Barr virus, the germinal centre and the development of Hodgkin’s lymphoma", Journal of General Virology, vol. 95, issue 10.1099/vir.0.066712-0, pp. 1861–1869, 2014. 1861.full_.pdf