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2. Diagnosis of Burkitt lymphoma using an algorithmic approach--applicable in both resource-poor and resource-rich countries

Author

Naresh, Kn, Ibrahim, Ha, Lazzi, S, Rince, P, Onorati, M, Ambrosio, Mr, BILHOU-NABERA, C, Amen, F, Reid, A, Mawanda, M, Calbi, V, Ogwang, M, Rogena, E, Byakika, B, Sayed, S, Moshi, E, Mwakigonja, A, Raphael, M, Magrath, I, and Leoncini, L.

Subjects
Adult, Diagnosis, Differential, Gene Expression Profiling, Health Resources, Humans, Lymphoma, Large B-Cell, Diffuse, Child, Burkitt Lymphoma, Algorithms, In Situ Hybridization, Fluorescence, Decision Support Techniques, Immunophenotyping
Abstract

Distinguishing Burkitt lymphoma (BL) from B cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma (DLBCL) and BL (DLBCL/BL), and DLBCL is challenging. We propose an immunohistochemistry and fluorescent in situ hybridization (FISH) based scoring system that is employed in three phases - Phase 1 (morphology with CD10 and BCL2 immunostains), Phase 2 (CD38, CD44 and Ki-67 immunostains) and Phase 3 (FISH on paraffin sections for MYC, BCL2, BCL6 and immunoglobulin family genes). The system was evaluated on 252 aggressive B-cell lymphomas from Europe and from sub-Saharan Africa. Using the algorithm, we determined a specific diagnosis of BL or not-BL in 82%, 92% and 95% cases at Phases 1, 2 and 3, respectively. In 3·4% cases, the algorithm was not completely applicable due to technical reasons. Overall, this approach led to a specific diagnosis of BL in 122 cases and to a specific diagnosis of either DLBCL or DLBCL/BL in 94% of cases that were not diagnosed as BL. We also evaluated the scoring system on 27 cases of BL confirmed on gene expression/microRNA expression profiling. Phase 1 of our scoring system led to a diagnosis of BL in 100% of these cases.

Published
2011

4. Routine assessment of hormonal receptor and her-2/neu status underscores the need for more therapeutic targets in Kenyan women with breast cancer

Author

Nyagol, J., Nyong O, A., Byakika, B., Muchiri, L., Cocco, M., DE SANTI MM, Spina, D., CRISTIANA BELLAN, STEFANO LAZZI, Kostopoulos, I., Luzi, Pietro, and Lorenzo LEONCINI

Subjects
Adult, Receptor, ErbB-2, Breast Neoplasms, Adenocarcinoma, Fluorescence, Lobular, Cohort Studies, ErbB-2, Predictive Value of Tests, Ductal, Receptors, 80 and over, Biomarkers, Tumor, Humans, Breast, Aged, Aged, 80 and over, Carcinoma, Ductal, Breast, Carcinoma, Lobular, Female, In Situ Hybridization, Fluorescence, Kenya, Middle Aged, Receptors, Estrogen, Receptors, Progesterone, In Situ Hybridization, Progesterone, Tumor, Carcinoma, Estrogen, Biomarkers, Receptor
Abstract

To report the expression of estrogen receptors, progesterone receptors and human epidermal growth factor receptor (Her-2/neu) in 158 Kenyan women with breast cancer and correlation with other prognostic indicators in this high-risk group. This study stressed the importance of routine assessment of the steroid receptors and Her-2/neu as a mode of therapeutic selection of patients for antihormonal or targeting monoclonal antibody (Herceptin) therapy, directed at the juxtamembrane domain of Her-2/neu protein in the developing countries such as Kenya.The study population consisted of 158 female patients with histologically confirmed breast carcinoma seen at the pathology department of The Nairobi Hospital. An immunohistochemical (IHC) study of ER, PR and Her-2/neu was conducted, followed by fluorescent in situ hybridization (FISH) validation for Her-2/neu gene amplification in cases initially scored as positive 2+ with IHC. Mastectomy samples registered at the pathology department of The Nairobi Hospital were used for this study. The study was approved by the institution's ethical review committee and informed consent obtainedfrom the concerned patients.In the studied cohort, positivity for both hormonal receptors and Her-2/neu was noted in 10 (6.33%) cases and negativity in 44 (27.85%) cases. Conversely, Her-2/neu negativity was noted in 32 (20.25%) cases with both steroid receptors positive and Her-2/neu positivity with both steroid receptors negative in 20 (12.66%) cases. Overall, no predictive factor was found in the Her-2/neu amplified 31/153 (20.26%) cases completely assessed with IHC and FISH. Grade III invasive ductal carcinomas, however, had a high prevalence of Her-2/neu overexpression. Association of both menopausal status (p = 0.044) and progesterone receptor status (p = 0.004) with high grade tumors were found to be statistically significant at 95% CI (p0.5). Consistent with other studies, Her-2/neu overexpression in this cohort was 20.26%.Her-2/neu positivity may activate ER expression through signaling kinases, and the combined target of mitogenic estrogen plus the monoclonal antibody therapy against Her-2/neu-overexpressing tumors expand chances of survival for patients in developing countries such as Kenya. The cost factor for these tests, selection for appropriate combined therapies and lack of awareness were noted as limiting factors for access to basic health care service and resulted in advanced tumor grade at time of patient presentation.

Published
2006

5. MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation.

Author

Leucci, E., Cocco, M., Onnis, A., Falco, G. De, Cleef, P. van, Bellan, C., Rijk, A.F. van, Nyagol, J., Byakika, B., Lazzi, S., Tosi, P., Krieken, H. van, Leoncini, L., Leucci, E., Cocco, M., Onnis, A., Falco, G. De, Cleef, P. van, Bellan, C., Rijk, A.F. van, Nyagol, J., Byakika, B., Lazzi, S., Tosi, P., Krieken, H. van, and Leoncini, L.

Abstract

Contains fulltext : 69103.pdf (publisher's version ) (Closed access), The molecular feature of Burkitt lymphoma (BL) is the translocation that places c-Myc under the control of immunoglobulin gene regulatory elements. However, there is accumulating evidence that some cases may lack an identifiable MYC translocation. In addition, during the EUROFISH project, aiming at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split-signal as well as a dual-fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level. Several studies have reported their involvement in cancer and their association with fragile sites in the genome. They have also been shown to control cell growth, differentiation, and apoptosis, suggesting that these molecules could act as tumour suppressors or oncogenes. Our results demonstrated a modulation of specific miRNAs. In particular, down-regulation of hsa-let-7c was observed in BL cases, compared to normal controls. More interestingly, hsa-mir-34b was found to be down-regulated only in BL cases that were negative for MYC translocation, suggesting that this event might be responsible for c-Myc deregulation in such cases. This hypothesis was further confirmed by our in vitro experiments, which demonstrated that increasing doses of synthetic hsa-mir-34b were able to modulate c-Myc expression. These results indicate for the first time that hsa-mir-34b may influence c-Myc expression in Burkitt lymphoma as the more common aberrant control exercised by the immunoglobulin enhancer locus.

Published
2008

8. Lymphomas in sub-Saharan Africa--what can we learn and how can we help in improving diagnosis, managing patients and fostering translational research?

Author

Naresh KN, Raphael M, Ayers L, Hurwitz N, Calbi V, Rogena E, Sayed S, Sherman O, Ibrahim HA, Lazzi S, Mourmouras V, Rince P, Githanga J, Byakika B, Moshi E, Durosinmi M, Olasode BJ, Oluwasola OA, Akang EE, Akenòva Y, Adde M, Magrath I, and Leoncini L

Subjects
Africa South of the Sahara epidemiology, Delivery of Health Care standards, Disease Management, Humans, International Cooperation, Lymphoma therapy, Lymphoma diagnosis, Lymphoma epidemiology, Quality Improvement, Translational Research, Biomedical methods
Abstract

Approximately 30 000 cases of non-Hodgkin lymphoma (NHL) occur in the equatorial belt of Africa each year. Apart from the fact that Burkitt lymphoma (BL) is very common among children and adolescents in Africa and that an epidemic of human immunodeficiency virus (HIV) infection is currently ongoing in this part of the world, very little is known about lymphomas in Africa. This review provides information regarding the current infrastructure for diagnostics in sub-Saharan Africa. The results on the diagnostic accuracy and on the distribution of different lymphoma subsets in sub-Saharan Africa were based on a review undertaken by a team of lymphoma experts on 159 fine needle aspirate samples and 467 histological samples during their visit to selected sub-Saharan African centres is presented. Among children (<18 years of age), BL accounted for 82% of all NHL, and among adults, diffuse large B-cell lymphoma accounted for 55% of all NHLs. Among adults, various lymphomas other than BL, including T-cell lymphomas, were encountered. The review also discusses the current strategies of the International Network of Cancer Treatment and Research on improving the diagnostic standards and management of lymphoma patients and in acquiring reliable clinical and pathology data in sub-Saharan Africa for fostering high-quality translational research., (© 2011 Blackwell Publishing Ltd.)

Published
2011
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9. Histology of specimens taken by prostatectomy and needle biopsy.

Author

Ngugi PM and Byakika B

Subjects
Aged, Aged, 80 and over, Humans, Male, Middle Aged, Prostate anatomy & histology, Prostate-Specific Antigen, Prostatic Hyperplasia pathology, Prostatic Neoplasms diagnosis, Retrospective Studies, Transurethral Resection of Prostate, Biopsy, Needle, Prostate pathology, Prostatectomy, Prostatic Neoplasms pathology
Abstract

Objectives: To determine the histology of the prostate in prostatectomy done for benign prostatic hypertrology (BPH), and prostate needle biopsy done for raised prostatic specific antigen (PSA)., Design: A retrospective study., Settings: Nairobi Hospital, Kenyatta National Hospital and Upper Hill Medical Centre., Subjects: The records of all the patients who had prostatectomy for BPH or trans-rectal needle biopsy of the prostate for raised prostatic specific antigen by the author and whose histology was determined at the Nairobi Hospital between May 2004 and December 2006., Results: A total of 108 specimens from 108 patients were sent to the laboratory. The ages of the patients ranged from 48 years to 83 years with a mean of 71.3 years. Of the 108 specimens submitted 82 were benign prostatic hypertrophy and 26 were carcinoma of the prostate. Out of 78 prostatectomy specimens ten (12.8%) had prostate cancer. In the needle biopsy group 16 out of 30 (53%) had prostate cancer. In total there were 82 (76%) patients with histology of benign prostate enlargement and 26 (24%) with histology of prostate cancer., Conclusion: Prostate cancer is a common disease in Kenya and a lot of it is important cancer as it will progress and cause death. In this poor resource setting it is possible to make diagnosis of prostate cancer even in the absence of transrectal ultrasound (TRUS) to help biopsy the prostate. The higher the prostatic specific antigen in asymptomatic patients the higher the yield of prostate cancer on biopsy of the prostate.

Published
2007
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