Breast cancer molecular diagnostics in Rwanda: a cost-minimization study of immunohistochemistry versus a novel GeneXpert® mRNA expression assay

Objective To compare the financial and time cost of breast cancer biomarker analysis by immunohistochemistry with that by the Xpert® STRAT4 assay. Methods We estimated costs (personnel, location, consumables and indirect) and time involved in breast cancer diagnosis at the Butaro Cancer Centre of Excellence, Rwanda, using time-driven activity-based costing. We performed a cost-minimization analysis to compare the cost of biomarker analysis for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status with immunohistochemistry versus STRAT4. We performed sensitivity analyses by altering laboratory-specific parameters for the two methods. Findings We estimated that breast cancer diagnosis in Rwanda costs 138.29 United States dollars (US$) per patient when conducting biomarker analysis by immunohistochemistry. At a realistic immunohistochemistry antibody utilization efficiency of 70%, biomarker analysis comprises 48.7% (US$ 67.33) of diagnostic costs and takes 33 min. We determined that biomarker analysis with STRAT4 yields a reduction in diagnosis cost of US$ 7.33 (10.9%; 7.33/67.33), and in pathologist and technician time of 20 min (60.6%; 20/33), per patient. Our sensitivity analysis revealed that no cost savings would be made in laboratories with antibody utilization efficiencies over 90%, or where only estrogen and/or progesterone receptor status are assessed; however, such operational efficiencies are unlikely, and more laboratories are pursuing human epidermal growth factor receptor-2 analysis as targeted therapies become increasingly available. Conclusion Breast cancer biomarker analysis with STRAT4 has the potential to reduce the required human and capital resources in subSaharan African laboratories, leading to improved treatment selection and better clinical outcomes.

Immunohistochemical Study and Clinicopathologic Correlation of Cox-2 and Her-2 Expression in Colorectal Carcinoma: A 5-Year Retrospective Study

BACKGROUND: Colorectal cancer (CRC) is the fourth most common cancer in Nigeria, and it affects mostly persons in their middle age. In a bid to gain some insight into the molecular characteristics of CRC in our environment, we set out to investigate the expression of COX-2 and HER-2 among Nigerian subjects. OBJECTIVES: To evaluate the expression of COX-2 and HER2 and determine their correlation with clinicopathologic parameters in surgically resected histologically diagnosed cases of colorectal cancer. METHODS: Fifty-three paraffin-embedded tissue blocks of colorectal resections and corresponding patient information were retrieved from the archives of the Anatomic and Molecular Pathology Department of Lagos University Teaching Hospital.A 4-micron slide section was obtained from each specimen and immunohistochemistry for COX-2 and HER-2 expression was performed. RESULTS: Mean age of cases was 53.9years with an almost equal M:F ratio of 1.12:1. Half of the cases were moderately differentiated adenocarcinoma and 17% were high grade tumors.Eighty three percent of the tumours showed positive cytoplasmic COX-2 expression and extremely low membranous HER-2 positivity was observed in 2%. There was no significant correlation between COX-2 expression and age, gender, tumour location, tumour size, depth of invasion or lymph node status.However, COX-2 expression revealed a significant correlation with tumour grade (p= 0.013). CONCLUSION: This study detects a high COX-2 and low HER2 expression in colorectal cancer using immunohistochemistry,suggesting a possible role for COX-2 in CRC pathogenesis.This report should trigger further investigations of both markers vis-à-vis the management of CRC in our environment. WAJM 2022; 39(11): 1134­1140.

Immunohistochemical Survey of Invasive Ductal Carcinoma of the Breast, using ER, PR, HER2 and KI-67 biomarkers, in Uyo, Nigeria

Background: Breast's Invasive Ductal Carcinoma (IDC), which is the commonest type of malignancy in females worldwide, can be characterized using immunohistochemistry in view of personalized cancer therapy. In this study, we aimed to determine the pattern of immunohistochemical profiles of IDC using oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 receptor (HER2) and proliferative index (Ki-67) biomarkers in our tertiary healthcare facility in Uyo, Akwa Ibom State, Nigeria given the dearth of its data in our environment. Materials and methods: We carried out a retrospective hospital-based immunohistochemical study of archival IDC tissue blocks over a four- and half-year period. Using systematic random sampling method, 64 formalin fixed paraffin embedded (FFPE) IDC tissue blocks were selected for this study. We carried out immunohistochemical evaluation using ER, PR, HER2 and Ki-67 biomarkers. Subsequently, we presented the results and classification schemes as text, tables, graphs, and photomicrographs. Results: We found that the proportion of expressions were ER-negative (88.7%), PR-negative (87.3%), HER2-negative (68.3%) and Ki-67 (<20%) being 83.6% respectively. The immunohistochemical-based classification which was done using combined immunohistochemical profiles of ER/PR/HER2 and ER/PR/HER2/Ki-67 biomarkers respectively, revealed five immunohistochemical-based subtypes. These subtypes were ER-positive luminal A (ER+/±PR+/HER2-) [5.56%], ER-positive luminal B (ER+/±PR+/HER2+) [5.56%], HER2-overexpression (ER-/±PR+/HER2+) [16.66%], Triple negative (ER-/PR-/HER2-) [66.67%] and Unclassified subtypes (ER-/PR+/HER2-) [5.56%]. Furthermore, these five subtypes were further subcategorized into low (Ki-67 <20%) and high (Ki-67 ≥20%) proliferation subtypes accordingly. Conclusion: The commonest pattern of immunohistochemical profile expression of IDC in Uyo was found to be the Triple negative subtype.

Immunohistochemical expression of cyclooxygenase-2 (COX-2) in breast cancer

Background: breast cancer (BC) is the most common type of diagnosed cancers in women. It is still the second leading cause of cancer-related death among women after lung cancer all over the world. Breast cancer is the first of top ten cancers in Egypt. It ranks as the first malignancy affecting females, contributing 30% of all female cancers. It affects 1 in 14 women during their life time. Aim: This study investigated the association between cyclooxygenase-2 (COX-2) expression in female breast cancer versus the expression of ER, PR, as well as its association with other established prognostic indicators like age, tumor size, lymph nodal status, stage, grade, lymphovascular invasion, insitu component and histological subtype, and aims to validate the role of overexpression of COX-2 as a prognostic marker in female patients with breast cancer in Egypt. Results: High significant correlation was found between lymph node metastasis, negative ER and PR cases and COX-2 expression. No significant correlation could be detected between age, tumor size, site, histologic type, grade, insitu component, LVI and COX-2 expression. Conclusion: Cyclooxygenase-2 has poor prognostic parameter in breast cancer, as it is over expressed in majority of breast carcinoma, especially with lymph node metastasis, ER and PR negative hormone receptor

Profil histo-épidemiologique des adénopathies cervicales chroniques au Congo - Brazzaville

Les adénopathies cervicales chroniques sont celles qui évoluent depuis plus de trois semaines de façon non résolutive. Elles posent un problème de diagnostic étiologique et peuvent annoncer une affection grave. Matériel et méthodes : Il s'est agi d'une étude descriptive et rétrospective allant du 01 juillet 2007 au 31 juillet 2017, soit une période de 10ans. Cette étude s'est déroulée dans les services d'ORL du CHU-B et de l'Hôpital Général Adolphe SICE. Résultats : Au total 100 cas d'adénopathies cervicales chroniques ont été colligés en 10 ans, soit une prévalence de 1,8%. Le sex-ratio était de 1,17 et la tranche d'âge la plus représentée était celle de 20 à 29 ans avec une moyenne d'âge de 30,8±15,8 ans. La plupart des patients avaient une poly-adénopathie cervicale et une fièvre comme signe associé (64% des cas). Les lésions histopathologiques en cause étaient la tuberculose ganglionnaire (49%), les lymphomes ganglionnaires (21%), les adénites réactionnelles (15%), les métastases des carcinomes (11%) l'histiocytose ganglionnaire (2%) et la maladie de CASTLEMAN (2%).Conclusion : La pathologie ganglionnaire cervicale au Congo reste dominée par la tuberculose, suivie des proliférations lymphoïdes malignes et réactionnelles. L'examen anatomo-pathologique standard est complété par une étude immunohistochimique pour un diagnostic étiologique plus précis

Breast cancer molecular subtypes among Moroccan women

Introduction: Breast cancer remains despite the therapeutic progress, the leading cause of death by cancer among women. It represents a group of very heterogeneous clinical, histopathological and molecular diseases. Molecular heterogeneity has been demonstrated by genomic analysis, even for similar histology cancers. Four subgroups of breast carcinomas are distinguished: Luminal A, Luminal B, HER2 over expression and Basal - like. The Immuno-histo-chemical analysis useip (estrogen receptors) RE, the PR (progesterone receptors), the ((Human Epidermal Growth Factor Receptor-2), the Ki67 (proliferation marker) HER2, CK5/6) has shown a subdivision into subgroups similar to those found by genomic analysis. These subgroups are different from the point of view of clinical course and response to adjuvant treatment.Objectives: The aim of this work is to study the molecular profile of the breast cancers by immunostaining on Moroccan series to a classification with a prognostic value allowing a treatment tailored to each group of patients. Furthermore, the molecular subgroups were correlated to other clinical and histological factors. Material and methods: It is a prospective study of the laboratory of Anatomy and Pathologic cytology of the children's Hospital, the service I of the maternity hospital in Rabat and in cooperation with the United Nations Centre of pathological anatomy. To do this, 88 cases of breast cancer together were diagnosed between January 1, 2010 and December 31, 2014, taking a period of five years. All tissue samples made subject study of Immuno-histo-chemistry with the following markers: RE, PR, HER2 and Ki67. Only negative triple cases (HR and HER2 negative) benefited from an additional marking with CK5/6 and EGFR to set the basal profile.Results: Series of 88 cases of mammary carcinomas observed on operating parts, ranged in age between 28 and 84 years old, with an average of 51 ± 12, 8. Carcinoma infiltrating non-specific (DOCTORS) was the most frequent (87.5%). Ranks histo-prognostic Scarff Bloom and Richardson (SBR) 2 and 3 respectively accounted for 45.5 and 51.1% of cases and only 2, 3% of the DOCTORS were grade 1. The Luminal B (53.4%) was under the most common molecular group, followed by Luminal A (23.9%), HER2 + (15.9%) and triple negative (6.8%). The correlation of molecular type of tumors with different prognostic factors showed only one significant connection with the SBR grade

Triple-negative breast cancer among ghanaian women seen at Korle-Bu teaching hospital

Background. Women with African ancestry in the United States and in continental Africa have been found to have exceptionally increased frequencies of triple-negative breast cancer (TNBC); prompting speculation that this risk may have an inherited basis and may at least partially explain breast cancer outcome disparities related to racial/ethnic identity. Our goal was to evaluate the breast cancers diagnosed in one of the largest health care facilities in western Africa; and to compare the frequencies as well as risk factors for TNBC versus non-TNBC. Methods. We reviewed all breast cancer cases that had immunohistochemistry (Novolink Detection system); in 2010. Results. The overall study population of 223 breast cancer cases was relatively young (median age 52.4?y); and most had palpable tumors larger than five centimeters in diameter. More than half were TNBC (130 cases; 58.3%). We observed similar frequencies of young age at diagnosis; stage at diagnosis; and tumor grade among cases of TNBC compared to cases of non-TNBC. Conclusion. Ghanaian breast cancer patients tend to have an advanced stage distribution and relatively young age at diagnosis. The triple-negative molecular marker pattern is the most common seen among these women; regardless of age; tumor grade; and stage of diagnosis. Additional research is necessary regarding the causes of TNBC; so that we can elucidate the reasons for its increased prevalence among women with African ancestry

L'immunohistochimie dans le diagnostic des tumeurs des tissus mous

Les tumeurs des tissus mous (TTM) sont un ensemble heteroclite; rare et de diagnostic histopathologique parfois difficile. L'immunohistochimie constitue un moyen complementaire d'un apport decisif. Nous rapportons ici une serie de 36 TTM; dont le diagnostic comparatif a ete fait entre Dakar et Bordeaux avec parfois utilisation de l'immunohistochimie (IHC) dans cette derniere ville pour la confirmation du diagnostic definitif. L'IHC a permis de redresser le type histologique dans 100 % des tumeurs benignes (2/2) et dans 60 % des tumeurs malignes (6/10). Bien etant une aide incontournable; l'IHC ne peut ni remplacer ni preceder un examen histologique standard qui represente la cle du diagnostic a condition que le pathologiste soit experimente

Classification moleculaire du cancer du sein au Maroc

La classification moleculaire des cancers du sein basee sur l'expression genique puis sur le profil proteique a permis de distinguer cinq groupes moleculaires: luminal A; luminal B; Her2/neu; basal-like et non-classees. L'objectif de cette etude realisee au CHU Hassan II de Fes est de classer 335 cancers du sein infiltrant en groupes moleculaires; puis de les correler avec les caracteristiques clinicopathologiques. Methodes Etude retrospective etalee sur 45 mois; comportant 335 patientes colligees au CHU pour le diagnostic et le suivi. Les tumeurs sont analysees histologiquement et classees apres une etude immunohistochimique en groupes: luminal A; luminal B; Her2+; basal-like et non-classees. Resultats 54.3 des tumeurs sont du groupe luminal A; 16des tumeurs sont du groupe luminal A; 16 luminal B; 11.3 Her2+; 11.3 basal-like et 7 non-classees. Le groupe luminal A renferme le plus faible taux de grade III; d'emboles vasculaires ainsi que de metastases ; alors que le groupe des non-classees et basal-like representent un taux eleve de grade III; une faible proportion d'emboles vasculaires et d'envahissement ganglionnaire. Ces facteurs sont significativement eleves dans les groupes luminal B et Her2+ avec un taux de survie globale de 78 et 76 respectivement. Dans le groupe luminal A; la survie globale des patientes est elevee (87) alors qu'elle n'est que de 49 dans le groupe des triples negatifs (basal-like et non-classes). Conclusion Le groupe luminal B est different du luminal A et il est de pronostic pejoratif vis a vis du groupe Her2+. Les caracteristiques clinicopatho- logiques concordent avec le profil moleculaire donc devraient etre pris en consideration comme facteurs pronostiques

Apport de l'immunohistochimie dans le diagnostic des lymphomes B agressifs chez les patients infectes ou non par le VIH en Republique democratique du Congo

Objectif. Determiner la contribution potentielle des techniques immunohistochimiques au diagnostic; et dans la prise en charge therapeutique des lymphomes-B agressifs chez des patients infectes ou non par le VIH; en R D Congo; dans le but de vulgarisation de cette approche; complementaire a l'etude morphologique; et indispensable pour le sous-typage de lymphomes; en particulier; de lymphomes-B agressifs. Methodes. Etude transversale et retrospective de 101 blocs de paraffine portant le diagnostic de lymphome et analyses entre 2005 et 2010; par des techniques morphologiques et immunohistochimiques; dans six laboratoires specialises de notre pays. Resultats. Les 81 blocs retenus; etaient tous CD20 positifs et CD3 negatifs; mais le profil etait variable pour d'autres marqueurs etudies. Le lymphome de Burkitt a ete identifie sur 40 blocs; incluant 7 sujets VIH+ (17;5); les lymphomes B diffus a grandes cellules; sur 35; avec 11; chez les VIH+ (31;4).Six lymphomes de forme intermediaire; dont 3; chez des sujets VIH+ (50). Conclusion. Cette etude a permis de classifier les lymphomes-B agressifs dans notre contexte; grace a l'immunohistochimie; justifiant le recours aux anticorps anti-CD20 pour leur traitement

Gastrointestinal Stromal Tumours at the University of NigeriaTeaching Hospital Enugu; Nigeria: an Immunohistochemical Study of GITMesenchymal Tumours

Mesenchymal tumours of the gastrointestinal tract (GIT) are uncommon. Recent progress in the understanding of the biology and origin of these tumours has led to their reclassification. A new subclass designated Gastrointestinal Stromal Tumours (GIST) is diagnosed based on the presence of a mutational over expression of c-kit protein that is thought to be critical in the pathogenesis of these tumours.This newclass of tumoursmay form the majority of gastrointestinal mesenchymal tumours. Even though the diagnosis of GIST is mainly based on positive staining with CD117; a minority of tumours with histological characteristics of GIST are CD117 negative and are classified asCD117 negativeGIST. In this first reviewof mesenchymalGITtumours fromNigeria;we present 11 cases ofmesenchymal tumours of the gastrointestinal tract seen within a six-year period at our centre. Immunohistochemistry was performed on 7 of themin which histological appearances suggested GIST. Only two cases had all the criteria defined in the consensus conference on the diagnosis ofGIST. Our findings; albeit in a very small sample; contrastswith what obtains in developed countries in the proportion of GIT mesenchymal tumours that are truly GIST. This raises a question to be answered on the true nature and proportion of gastrointestinal strumal tumours among GITtumours inNigerian patients

p53 Expression in Colorectal Carcinoma in Relation to Histopathological Features in Ugandan Patients

Background: It has been shown that colorectal carcinoma is increasing in incidence in African countries. This could be due to change in life style. Molecular patho- genesis of colorectal cancer commonly involves mutation in p53 gene which leads to expression of p53 protein in tumor cells. Expression of p53 protein has been associated with poor clinical outcome and reduced survival in patients. Objective: This was a retrospective laboratory based study carried out in the Department of Pathology Makerere University; Kampala; Uganda. The aim of the study was to evaluate the expression of p53 protein in colorectal carcinoma in Ugandan patients; specifically its association with histological types; degree of differentiation; sites of the tumor and demographic characteristics of the patients. Methods: Immuno- histochemistry was carried out on 109 patient's paraffin embedded tissue blocks of colorectal carcinoma diagnosed in the Pathology Department; Faculty of Medicine Makerere University Kampala during the period 1995 to 2005. The indirect immunoperoxidase method using monoclonal antibody p53 DO-7 and Envision + Dual link system-HRP to detect p53 expression was used. Haematoxylin and eosin stain was used for evaluation of histological types and degree of differentiation of the tumors. Topography of the tumors and demographic data were obtained from accompanying histological request forms. Results: Out of 109 patient's tissue blocks that were studied; 61 cases (56) expressed p53 protein in the nucleus of malignant cells. Right sided colonic tumors were commoner (53.2) than left sided colonic tumors (46.8). p53 protein was expressed more in left sided colonic tumors with a significant difference (p0.05); it was also expressed more in well differentiated tumors and non mucinous adenocarcinomas but with no significant difference (p0.05). p53 expression was not affected by age or sex. Conclusion: Frequency of p53 protein expression in Ugandan patients did not differ from that reported in the other parts of the world. It was expressed more in the left sided colonic tumors and this could support the hypothesis that right and left colonic tumors could have different pathogenesis and probably also responsible for difference in prognosis in these two topographic sites

Immunocytochemistry in the diagnosis of small blue cell tumours of childhood

Objective: This study attempts to define a limited; cost effective; reliable primary panel of antibodies for immunohistology; as an adjunct to morphological features; for the diagnosis of Small Blue Cell Tumors (SBCT) which would be convenient for use in low resource settings to improve their diagnostic accuracy. The choice of antibodies is based on the common childhood tumors in Ibadan and limited by financial constraints and availability of antibodies. Materials et methods: Twenty-five representative cases of previously diagnosed small blue cell tumours of childhood were selected from the file of the Department of Pathology; University College Hospital; Ibadan. The retrieved blocks were cut and stained with antibodies to desmin; leucocyte common antigen; cytokeratin; chromogranin; neuron-specific-enolase; vimentin and neurofilament using the avidin-biotin technique as previously described. Results: Of the 25 cases studied 24 (96) gave interpretable immunostaining reaction and the immunophenotype of these were defined. The staining quality equaled that produced on the control well-fixed positive control sections. The final diagnosis of six of the 25 cases changed based on immunostaining. Four cases previously diagnosed as lymphoma were confirmed to be rhabdomyosarcoma (3 cases) and neuroblastoma; one case each of rhabdomyosarcoma and neuroblastoma were both reclassified as lymphoma. Conclusion: Based on our findings; the use of a small first-line panel of antibodies to leucocyte common antigen; desmin and neuron-specific-enolase are ideal for immunohistochemical discrimination of SBCT; as an adjunct to morphology; in low-resource settings

Comparison of immunohistochemical and modified Giemsa stains for demonstration of Helicobacter pylori infection in an African population

Modified Giemsa staining has been favoured by many researchers because it is easy to perform but; like many other stains; demonstration of the bacteria depends on its morphology. It has been arged in some research circles that some of the organisms in the gastric mucosa may not be true H.pylori. Immunohisochemical techniques have been developed and make use of anti H.pylori antibody; which reacts; with somatic antigens of the whole bacteria and have been found to correlate well with the presence of the bacteria. Objective: to ascertain the efficacy of modified Giemsa stain in an African setting where H.pylori seems quite prevalent. Study design: A laboratory - based study of two diagnostic tests in which modified Giemsa stain was compared with immunohistochemistry. Methods: A total of 48 consecutive autopsy cases with no upper gastro intestinal diseases had their gastric mucosa stained for demonstration of H.pylori using both modified Giemsa and immunohistochemical staining techniques. Results: Twenty-seven cases of H.pylori were demonstrated by both techniques and 14 cases were not identified by the two staining methods. In 2 cases immunostain could not demonstrate the bacteria but they were identified with modified Giemsa stain while in 5 cases the bacteria were identified by immunostain but not with modified Giemsa stain. The sensitivity of modified Giemsa stain was 85(CI 66.5-98.8) while the specificity was 89(CI 60.4-97.8). The positive predictive value of modified Giemsa stain was 93CI 75 - 98.8) while the negative predictive value was 74(CI 48.6-89.9). The kappa statistic comparing the 2 stains was 0.69 (p-value 0.00001) giving a good agreement between the two tests. Conclusion: With the above results the modified Giemsa stain; which is readily available in most African laboratories; is recommended for diagnosis of H.pylori; a prevalent infection in Africa