Publications
152 results found
Zeller C, Dai W, Curry E, et al., 2013, The DNA Methylomes of Serous Borderline Tumors Reveal Subgroups With Malignant- or Benign-Like Profiles, AMERICAN JOURNAL OF PATHOLOGY, Vol: 182, Pages: 668-677, ISSN: 0002-9440
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- Citations: 11
Ganesan R, Brown LJR, Kehoe S, et al., 2013, The role of frozen sections in gynaecological oncology: survey of practice in the United Kingdom, EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, Vol: 166, Pages: 204-208, ISSN: 0301-2115
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- Citations: 14
Wang J, El-Masry N, Talbot I, et al., 2013, Expression profiling of proliferation and apoptotic markers along the adenoma-carcinoma sequence in familial adenomatous polyposis patients, Gastroenterology Research and Practice, Vol: 2013, ISSN: 1687-6121
Familial adenomatous polyposis (FAP) patients have a germline mutation in the adenomatous polyposis coli (APC) gene. The APC protein interacts with beta-catenin, resulting in the activation of the Wnt signalling pathway. This results in alterations in cell proliferation and apoptosis. We investigated the expression of beta-catenin and related proliferation and apoptotic factors in FAP patients, exploring the expression along the adenoma-carcinoma sequence. Methods. The expression of beta-catenin, p53, bcl-2, cyclin-D1, caspase-3, CD10, and Ki-67 proteins was studied by immunohistochemistry in samples of colonic nonneoplastic mucosa ( ), adenomas ( ), and adenocarcinomas ( ) from each of the16 FAP patients. Results. The expression of beta-catenin, caspase-3, cyclin-D1, and Ki-67 was increased in both adenomas and carcinomas in FAP patients, compared with normal mucosa. p53 and CD10 expression was only slightly increased in adenomas, but more frequently expressed in carcinomas. Bcl-2 expression was increased in adenomas, but decreased in carcinomas. Conclusion. This is the first study investigating collectively the expression of these molecules together in nonneoplastic mucosa, adenomas, and carcinomas from FAP patients. We find that beta-catenin and related proliferative and apoptotic factors (cyclin-D1, bcl-2, caspase-3, and Ki-67) are expressed early in the sequence, in adenomas. However, p53 and CD10 are often expressed later in the sequence, in carcinomas.
Balasubramaniam ES, Van Noorden S, El-Bahrawy M, 2012, The expression of interleukin (IL)-6, IL-8, and their receptors in fallopian tubes with ectopic tubal gestation, FERTILITY AND STERILITY, Vol: 98, Pages: 898-904, ISSN: 0015-0282
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- Citations: 20
Wang J, Hollingshead J, El-Masry N, et al., 2012, Expression of EGFR, HER2, phosphorylated ERK and phosphorylated MEK in colonic neoplasms of familial adenomatous polyposis patients., J Gastrointest Cancer, Vol: 43, Pages: 444-455
PURPOSE: The expression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis in sporadic colorectal carcinoma (CRC). EGFR inhibitors are approved for the treatment of refractory CRC. The aim of this study was to investigate the expression of EGFR and HER2 and downstream extracellular signal regulated kinase (ERK) and mitogen activated protein kinase (MAPK) in non-neoplastic colonic mucosa, adenomas and carcinomas from familial adenomatous polyposis coli (FAP) patients, exploring the expression along the adenoma-carcinoma sequence. METHODS: The expression of EGFR, HER2, phosphorylated MAPK/ERK kinase (pMEK) and phosphorylated ERK (pERK) proteins was studied by immunohistochemistry in samples of colonic non-neoplastic mucosa (n = 65), adenomas (n = 149) and adenocarcinomas (n = 16) from each of the 16 FAP patients. RESULTS: For HER2, only weak cytoplasmic expression was seen in 8% of adenomas, 6% of carcinomas and 3% of the non-neoplastic mucosa. EGFR was expressed in non-neoplastic mucosa, adenomas and carcinomas with a statistically significant increase in expression in adenomas compared with non-neoplastic mucosa (p < 0.001). There was also a statistically significant increase in nuclear staining intensity for pERK (p < 0.001) and pMEK (p < 0.001) in adenomas compared to non-neoplastic mucosa. CONCLUSIONS: This is the first study investigating the expression of these receptors in non-neoplastic mucosa, adenomas and carcinomas from FAP patients. HER2 is not upregulated in the tumours of FAP patients, while EGFR appears to be upregulated in most adenomas and carcinomas, with associated upregulation of pERK and pMEK. We conclude that EGFR and downstream members of its signalling pathway, but not HER2, may be potential therapeutic targets in FAP patients.
Ewington L, Taylor A, Sriraksa R, et al., 2012, The expression of interleukin-8 and interleukin-8 receptors in endometrial carcinoma, CYTOKINE, Vol: 59, Pages: 417-422, ISSN: 1043-4666
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- Citations: 23
Guppy NJ, El-Bahrawy ME, Kocher HM, et al., 2012, Trefoil Factor Family Peptides in Normal and Diseased Human Pancreas, PANCREAS, Vol: 41, Pages: 888-896, ISSN: 0885-3177
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- Citations: 18
Mckie AB, Vaughan S, Zanini E, et al., 2012, The OPCML Tumor Suppressor Functions as a Cell Surface Repressor–Adaptor, Negatively Regulating Receptor Tyrosine Kinases in Epithelial Ovarian Cancer, Cancer Discovery
Wang J, El-Bahrawy M, 2011, The diagnostic accuracy of cervical biopsies in determining cervical lesions: an audit., Pathologica, Vol: 103, Pages: 331-336, ISSN: 0031-2983
OBJECTIVE: The present audit was carried out to assess the diagnostic accuracy of cervical punch biopsy during colposcopy in comparison with diagnosis from subsequent cone excision. DESIGN AND SETTING: Retrospective analysis was performed by examining the histopathology reports for paired cervical punch biopsies and cervical cone excisions for cases reported from April 2004 to March 2005 (when cervical biopsies and cones were reported by general pathologists) and from January to December 2008 (when reporting by specialist gynaecological pathologists was instituted). SAMPLE: 150 women had both cervical punch and cone biopsies performed in the 2004-2005 period, while 149 women had both biopsies performed in 2008. MAIN OUTCOME MEASURES AND RESULTS: In 2004-5, the rate of consistent diagnosis was 68.7%, compared with 75.8% in 2008. This was due to a decrease in the rates of overdiagnosis (16.7% vs. 14.8%) and underdiagnosis (14.7% vs. 9.4%), which was statistically significant. The sensitivity rates for 2004-5 and 2008 were 87.5% and 89.7%, and the specificity rates for the same periods were 39.8% and 39.4% respectively. CONCLUSIONS: This audit highlights the importance of planning patient management on the basis of co-ordinated information from smear results, history, colposcopy findings and cervical biopsies. The introduction of specialist gynaecological histopathology reporting has significantly improved the rates of consistent diagnosis.
Adam J, Hatipoglu E, O'Flaherty L, et al., 2011, Renal Cyst Formation in Fh1-Deficient Mice Is Independent of the Hif/Phd Pathway: Roles for Fumarate in KEAP1 Succination and Nrf2 Signaling, CANCER CELL, Vol: 20, Pages: 524-537, ISSN: 1535-6108
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- Citations: 422
Horimoto Y, Hartman J, Millour J, et al., 2011, ERβ1 Represses FOXM1 Expression through Targeting ERα to Control Cell Proliferation in Breast Cancer, AMERICAN JOURNAL OF PATHOLOGY, Vol: 179, Pages: 1148-1156, ISSN: 0002-9440
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- Citations: 29
Bardella C, El-Bahrawy M, Frizzell N, et al., 2011, Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status, JOURNAL OF PATHOLOGY, Vol: 225, Pages: 4-11, ISSN: 0022-3417
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- Citations: 188
Ewington LJ, Taylor A, Sriraksa R, et al., 2011, The Expression of Interleukin-8 and the Interleukin-8 Receptors (CXCR1 and CXCR2) in Endometrial Carcinoma, 6th Joint Meeting of the British Division of the International-Academy-of-Pathology-and-the-Pathological-Society-of-Great-Britain-and-Ireland, Publisher: WILEY-BLACKWELL, Pages: S14-S14, ISSN: 0022-3417
El-Bahrawy M, 2011, Expression of p16 in post-radiotherapy cervical biopsies, HISTOPATHOLOGY, Vol: 58, Pages: 1174-1176, ISSN: 0309-0167
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- Citations: 1
Gungor H, Saleem A, Agarwal R, et al., 2011, Pharmacokinetic (PK)/pharmacodynamic (PD) analysis of escalating repeat doses of the AKT inhibitor GSK2141795 (GSK795) in patients (pts) with ovarian cancer, ASCO 2011
Background: GSK795 is a potent, ATP-competitive, pan AKT inhibitor. The purpose of this study was to characterize the relationship between AKT inhibition by GSK795 and downstream effects in platinum resistant ovarian cancer pts. Methods: Pts with recurrent platinum-resistant ovarian cancer received 25, 50 or 75mg of oral GSK795 daily. Dynamic FDG-PET scans and paired tumor biopsies (PTB) were performed prior to first dose and at 2 and/or 4 weeks post treatment. Semi-quantitative (SUV) and quantitative (Ki, MRglu) PET PD parameters were derived. PTB were analyzed by immunohistochemistry (IHC) for PD marker expression. PK samples were obtained in parallel. Response was monitored by RECIST and CA125 criteria. Results: 12 pts have been treated on study: 4 at 25mg, 4 at 50mg and 4 at 75mg. After completion of the 2 or 4 week post-treatment PD assessment, all eligible pts underwent intra-subject dose escalation to 75mg. The most common drug-related adverse events ( 10%) were decreased appetite (18%) and vomiting (18%), all G1/2. Mean Cmax and AUC24 increased with increasing doses and increased 1.2-fold from Week 2 to Week 4 where 2 and 4 week doses were the same. Median Tmax was 4 h. Overall tumor FDG metabolism decreased in 71% of tumors with treatment, although inter- and intra-patient variability in tumor uptake measurements following therapy was seen. There was no clear temporal or dose-response effect in FDG uptake. IHC analysis of PTB from 5 pts dosed at either 50 or75mg indicated that pAKT levels increased in 2/2 pts dosed at 75mg, pPRAS40 levels decreased in 4/5 pts, and Ki67 levels decreased in 4/5 pts after treatment with GSK795. 8/12 pts had stable disease and 4/12 had progressive disease by RECIST criteria at week 4. Currently 4 pts are still on the study, 2 > 24 weeks, with tumor regressions of 26% and 11% and CA125 decreases of 70% and 58% respectively. Conclusions: A dose response relationship between changes in FDG-PET and GSK795 was not observed in pts
Gungor H, Saleem A, Agarwal R, et al., 2011, Pharmacokinetic (PK)/pharmacodynamic (PD) analysis of escalating repeat doses of the AKT inhibitor GSK2141795 (GSK795) in patients (pts) with ovarian cancer., JOURNAL OF CLINICAL ONCOLOGY, Vol: 29, ISSN: 0732-183X
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- Citations: 7
Sriraksa R, Zeller C, El-Bahrawy MA, et al., 2011, CpG-island methylation study of liver fluke-related cholangiocarcinoma, British Journal of Cancer, Vol: 104, Pages: 1313-1318, ISSN: 0007-0920
Background:Genetic changes have been widely reported in association with cholangiocarcinoma (CCA), while epigenetic changes are poorly characterised. We aimed to further evaluate CpG-island hypermethylation in CCA at candidate loci, which may have potential as diagnostic or prognostic biomarkers.Methods:We analysed methylation of 26 CpG-islands in 102 liver fluke related-CCA and 29 adjacent normal samples using methylation-specific PCR (MSP). Methylation of interest loci was confirmed using pyrosequencing and/or combined bisulfite restriction analysis, and protein expression by immunohistochemistry.Results:A number of CpG-islands (OPCML, SFRP1, HIC1, PTEN and DcR1) showed frequency of hypermethylation in >28% of CCA, but not adjacent normal tissues. The results showed that 91% of CCA were methylated in at least one CpG-island. The OPCML was the most frequently methylated locus (72.5%) and was more frequently methylated in less differentiated CCA. Patients with methylated DcR1 had significantly longer overall survival (Median; 41.7 vs 21.7 weeks, P=0.027). Low-protein expression was found in >70% of CCA with methylation of OPCML or DcR1.Conclusion:Aberrant hypermethylation of certain loci is a common event in liver fluke-related CCA and may potentially contribute to cholangiocarcinogenesis. The OPCML and DcR1 might serve as methylation biomarkers in CCA that can be readily examined by MSP.
Hollingshead JRF, Wang J, El-Masry N, et al., 2011, Expression of the Phosphorylated ERK and MEK MAPKs and Upstream Growth Factor Receptors in Adenomas and Carcinomas of Patients with Familial Adenomatous Polyposis, 199th Scientific Meeting of the Pathological-Society-of-Great-Britain-and-Ireland, Publisher: WILEY-BLACKWELL, Pages: S17-S17, ISSN: 0022-3417
Wang JEH, El-Bahrawy M, 2011, An Audit on the Diagnostic Accuracy of Cervical Biopsies in Determining Cervical Lesions, 199th Scientific Meeting of the Pathological-Society-of-Great-Britain-and-Ireland, Publisher: WILEY-BLACKWELL, Pages: S14-S14, ISSN: 0022-3417
Tan DSP, Iravani M, McCluggage WG, et al., 2011, Genomic Analysis Reveals the Molecular Heterogeneity of Ovarian Clear Cell Carcinomas, CLINICAL CANCER RESEARCH, Vol: 17, Pages: 1521-1534, ISSN: 1078-0432
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- Citations: 99
Mashali N, Awad AT, Trevisan G, et al., 2011, Renal leiomyoma., Pathologica, Vol: 103, Pages: 22-24, ISSN: 0031-2983
Renal leiomyomas are rare benign tumours, which are usually small in size and incidentally discovered in most of cases. We report a case of giant renal leiomyoma encasing the right kidney in a 55 year old lady. We review the spectrum of features seen in reported leiomyomas on imaging and gross appearance. We discuss the differential diagnosis and highlight the fact that renal leiomyoma, although rare, must be considered in the differential diagnosis of spindle cell lesions of the kidney and that this tumour may present as a huge renal mass.
El-Bahrawy M, 2011, α-Fetoprotein-Producing Non-Germ Cell Tumors of the Urological System., Rev Urol, Vol: 13, Pages: 14-19
Elevated serum levels of α-fetoprotein (AFP), a fetal serum protein, occur mainly in the development of hepatocellular carcinoma (HCC) or germ cell tumors, mainly yolk sac tumor. Rarely, other tumors of the urological system produce AFP. This article reviews the AFP-producing non-germ cell tumors of the urological tract reported to date. These include different types of tumors of the adrenal glands, kidney, ureter, urinary bladder, and testis. It is important for pathologists, urologists, and oncologists to be aware of such cases as the diagnosis affects the management plan for the patient.
Ashrafian H, O'Flaherty L, Adam J, et al., 2010, Expression Profiling in Progressive Stages of Fumarate-Hydratase Deficiency: The Contribution of Metabolic Changes to Tumorigenesis, CANCER RESEARCH, Vol: 70, Pages: 9153-9165, ISSN: 0008-5472
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- Citations: 50
Qureshi YA, Guppy NJ, Otto WR, et al., 2010, The expression and co-localisation of trefoil factor family peptides and mucins in normal and diseased pancreas, Annual Meeting of the Society-of-Academic-and-Research-Surgeons, Publisher: JOHN WILEY & SONS LTD, Pages: 28-28, ISSN: 0007-1323
Smith R, Moss J, Shore I, et al., 2010, Juvenile granulosa cell tumour with hepatocyte-like cells and raised serum alpha-fetoprotein, HISTOPATHOLOGY, Vol: 57, Pages: 637-641, ISSN: 0309-0167
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- Citations: 1
El-Bahrawy M, 2010, Alpha-fetoprotein-producing non-germ cell tumours of the female genital tract, EUROPEAN JOURNAL OF CANCER, Vol: 46, Pages: 1317-1322, ISSN: 0959-8049
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- Citations: 35
Slesser AAP, Paige A, Gabra H, et al., 2010, The expression of WWOX in pancreatic adenocarcinoma, 6th International Conference on Clinical Cancer Prevention (SG-CAP 2010), Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 10-10, ISSN: 1359-6349
El-Bahrawy MA, Khorsandy S, Williamson R, et al., 2010, Spindle Cell Solid Pseudopapillary Tumor of the Pancreas <i>A Newly Described Variant</i>, PANCREAS, Vol: 39, Pages: 255-257, ISSN: 0885-3177
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- Citations: 2
Hussain F, Wang J, Ahmed R, et al., 2010, The expression of IL-8 and IL-8 receptors in pancreatic adenocarcinomas and pancreatic neuroendocrine tumours, CYTOKINE, Vol: 49, Pages: 134-140, ISSN: 1043-4666
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- Citations: 30
Barker D, Sharma R, McIndoe A, et al., 2010, An Unusual Case of Sex Cord Tumor With Annular Tubules With Malignant Transformation in a Patient With Peutz-Jeghers Syndrome, INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY, Vol: 29, Pages: 27-32, ISSN: 0277-1691
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- Citations: 17
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