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.

The End of the Road for Prostate Specific Antigen Testing?

Many candidate biomarkers for diagnosis of prostate cancer have been investigated; but prostate-specific antigen (PSA) testing remains the frontline test for both mass screening and individual clinical testing. Although the PSA test is cost-effective; analytically reliable; and flexibly high throughput; it has a very weak correlation with prostate malignancy. This has resulted in over-diagnosis and over-treatment of patients leading to costly economic; social; and psychological impacts. PSA testing lacks the ability to molecularly characterize prostate diseases and define aggressiveness and lethality; which are necessary to influence choice of treatment. Therefore; newer molecular tests are beginning to replace the PSA tests. The prostate cancer antigen 3 test has shown superiority and is now widely used. The recently reported sarcosine urine test; the already delineated TMPRSS2: ETS fusion genes; the glutathione-S-transferase P1 serum marker; and enhancer of zeste homolog 2 biomarker may also help improve diagnosis and prognostication of prostate cancer. The analytical trend is toward a multiplex testing format using molecular and/or proteomic techniques that are reliable; accurate; reproducible; and ensure rapid quantitation. Therefore; validation of these newer biomarkers and their assays are necessary for both large-scale clinical trials and clinical utility

Intérêt des marqueurs tumoraux sériques dans les cancers digestifs

Les marqueurs tumoraux sont des composés produits par les cellules cancéreuses ou leur environnement se retrouvant en quantité suffisante dans le sang, les urines et les liquides d'effusion. Les marqueurs les plus utilisés en pathologie digestive sont l'antigène carcino-embryonnaire (ACE), l'alpha foetoproteine (_FP) et le CA19-19. Le but de notre travail est de discuter l'intérêt de ces trois marqueurs dans le dépistage, le suivi et le pronostic des cancers gastriques, pancréatiques, colorectaux et hépatiques.La faible sensibilité et l'existence de faux positifs rendent parfois ces marqueurs impropres à une stratégie de dépistage. Par contre, seul l'_FP a une valeur diagnostique dans les hépato carcinomes pour les populations à haut risque. L'ACE et le CA19-9 ont une bonne sensibilité et une spécificité relative qui leur permettent de suivre l'évolution des cancers digestifs en particulier les cancers colorectaux. Ils constituent les meilleurs marqueurs pour évaluer le pronostic, l'efficacité thérapeutique et pour dépister les récidives de façon précoce. Leur association est justifiée et permet d'atteindre 91% de spécificité et 76% de sensibilité.Devant la place occupée par la biologie dans le diagnostic, le pronostic et le suivi des cancers digestifs par le dosage des marqueurs tumoraux, nous nous devons que de reconnaître tant leurs performances que leurs limites

Calcium; Inorganic Phosphates; Alkaline and Acid Phosphatase Activities in Breast Cancer Patients in Calabar; Nigeria

Background: Breast cancer is the commonest malignancy of women in Nigeria. Change in serum levels of some biochemical parameters could assist diagnosis and follow-up of breast cancer. Objective: To determine serum levels of calcium; inorganic phosphates; alkaline phosphatase (ALP) and acid phosphatase (ACP) activities in patients with breast cancer; and change in the serum levels over time. Methods: Total serum calcium and inorganic phosphates; and serum ALP and ACP activities were determined in 25women with breast cancer and 25 age-matched controls using colorimetric and enzymatic methods; over 6 months with bimonthly analysis. Results: The serum calcium level; increases in serum calcium levels; ALP and ACP activities in the study group with time (p0.05); whereas no significant increase was observed in the control group.Conclusion: Breast cancer patients have higher calcium levels and higher ALP and ACP activities. The increase in the levelsof these parameters with the levelsofthese parameters with time shows that they could be of importance in monitoring treatment and disease progress in a resource-poor setting

Value of P53 protein as a tumor marker in patients with transitional cell bladder cancer

Objective: The aim of this work is to determine the value of P53 as a biochemical marker in patients with bladder cancer. Patients and Methods: This study was conducted on 30 patients with transitional cell carcinoma (TCC) of different grades and 10 healthy men as a control group who had been admitted to the Urology Department; Benha Faculty of Medicine between August 1999 and November 2001. The mean age of the patients was 56.3 years (range 38-80 years). They were evaluated by history taking; clinical examination; laboratory investigations; radiological examination and cysto-scopy-guided biopsies. P53 was determined in the serum preoperatively and postoperatively after 21 days and 6 months; as well as in the tissue specimens taken by transurethral resection or by radical cystectomy. Results: The mean serum P53 value in the control group was 10.0 + 1.83 Pg/ml. In the patients with grade-1 tumors it was 25.6 + 4.8 Pg/ml compared to 44.8 + 14.73 Pg/ml and 131.1 + 15.28 Pg/ml for grade-2 and grade-3 tumors; respectively (P 0.05). In tumors larger than 2 cm the mean serum P53 value was 87.54 + 10.81 Pg/ml; while in tumors less than 2 cm it was 32.91 + 2.32 Pg/ml (P 0.05). The mean serum P53 value in a single tumor was 27.8 + 7.1 Pg/ml compared to 102.3 + 20.4 Pg/ml in multiple tumors (P 0.05). On follow-up after 21 days the mean serum P53 value was 14.0 + 2.71 Pg/ml in grade-1 tumors; 17.0 + 3.79 Pg in grade-2 and 55.3 + 12.4 Pg/ml in grade-3 tumors (P 0.05). Eleven patients developed recurrence; their mean serum P53 was 125.6 + 13.46 Pg/ml preoperatively and significantly decreased to 59.9 + 18.2 Pg/ml postoperatively; but then rose again to 91.5 + 20.1 Pg/ml. The mean P53 in the tissues of the control group was 11.3 + 2.31 Pg/ml; while the tissues of the cancer patients showed values of 29.8 + 4.42 Pg/ml; 46.6 + 11.08 and 140.2 + 14.85 Pg/ml for grade-1; grade-2 and grade-3 tumors; respectively (P 0.05). Conclusion: P53 seems to be a promising tumor marker for transitional cell bladder cancer and a valuable tool for identifying subgroups of patients that may have a poor prognosis

Serum transforming growth factor Beta1 and prostate specific antigen as markers for localized and metastatic prostate cancer

Objectives: To assess any additional benefits of the estimation of serum TGF Beta1 over serum PSA for differentiating localized from metastatic prostatic carcinoma. Patients and Methods: Forty-seven prostate cancer patients (23 with and 24 without metastases) and ten controls were included in the study. Serum PSA was estimated using the chemiluminescent immunometric assay; and serum TGF Beta1 was assessed using the enzyme immunoassay.Results: The mean serum PSA in the localized and metastatic disease groups were significantly higher than that in the control group (p0.001; p0.001 respectively); while the mean serum TGF Beta1 in the metastatic disease group only was significantly higher than in the control: group (p0.01). The mean serum PSA and TGF Beta1 in the metastatic disease group were significantly higher than the values in the localized disease group (p0.001; p0.001 respectively). Serum PSA was directly correlated with Gleason score in both patient groups (localized group: r