Serum tumour marker CA 125 in monitoring of ovarian cancer during first-line chemotherapy

The value of the serum tumour marker CA 125 to date has been in the monitoring of ovarian cancer patients for response to therapy and for recurrence of disease. However, despite the availability of serial data on CA 125, the problem of interpreting a change over time is still unsolved. The aim of this study was to assess the ability of CA 125 to monitor patients with ovarian cancer during postoperative chemotherapy. 255 patients with stage IC-IV ovarian cancer were allocated to the tumour marker monitoring study. The evaluation of CA 125 information was based on the analytical imprecision, the normal intra-individual biological variation, the sampling interval, and the cut-off value. Additionally, a new assessment criterion based upon an increment of 2.5 times the baseline CA 125 concentration confirmed by a third measurement was elaborated and the utility investigated. The efficiency of CA 125 for identifying progression and non-progression during first-line chemotherapy was 91.9%. The median lead time for true positive results was 41 days. Using the new elaborated criterion the efficiency of CA 125 for identifying progression and non-progression during first-line chemotherapy was 90.5%. The median lead time for true positive results was 35 days. CA 125 gave reliable prediction of progressive disease during postoperative chemotherapy. The results indicate a high applicability of the presented progression criteria during CA 125 monitoring of patients with changing activity of ovarian cancer. © 2001 Cancer Research Campaign www.bjcancer.co

Gender-partitioned patient medians of serum albumin requested by general practitioners for the assessment of analytical stability

AbstractBackground:Recently, the use of separate gender-partitioned patient medians of serum sodium has revealed potential for monitoring analytical stability within the optimum analytical performance specifications for laboratory medicine. The serum albumin concentration depends on whether a patient is sitting or recumbent during phlebotomy. We therefore investigated only examinations requested by general practitioners (GPs) to provide data from sitting patients.Methods:Weekly and monthly patient medians of serum albumin requested by GP for both male and female patients were calculated from the raw data obtained from three analysers in the hospital laboratory on examination of samples from those &gt;18 years. The half-range of medians were applied as an estimate of the maximum bias. Further, the ratios between the two medians were calculated (females/males).Results:The medians for male and female patients were closely related despite considerable variation due to the current analytical variation. This relationship was confirmed by the calculated half-range for the monthly ratio between the genders of 0.44%, which surpasses the optimum analytical performance specification for bias of serum albumin (0.72%). The weekly ratio had a half-range of 1.83%, which surpasses the minimum analytical performance specifications of 2.15%.Conclusions:Monthly gender-partitioned patient medians of serum albumin are useful for monitoring of long-term analytical stability, where the gender medians are two independent estimates of changes in (delta) bias: only results requested by GP are of value in this application to ensure that all patients are sitting during phlebotomy.</jats:sec

Separate patient serum sodium medians from males and females provide independent information on analytical bias

AbstractBackground:During monitoring of monthly medians of results from patients undertaken to assess analytical stability in routine laboratory performance, the medians for serum sodium for male and female patients were found to be significantly related.Methods:Daily, weekly and monthly patient medians of serum sodium for both male and female patients were calculated from results obtained on samples from the population &gt;18 years on three analysers in the hospital laboratory. The half-range of medians was applied as an estimate of the maximum bias. Further, the ratios between the two medians were calculated.Results:The medians of both genders demonstrated dispersions over time, but they were closely connected in like patterns, which were confirmed by the half-range of the ratios of medians for males and females that varied from 0.36% for daily, 0.14% for weekly and 0.036% for monthly ratios over all instruments.Conclusions:The tight relationship between the gender medians for serum sodium is only possible when raw laboratory data are used for calculation. The two patient medians can be used to confirm both and are useful as independent estimates of analytical bias during constant calibration periods. In contrast to the gender combined median, the estimate of analytical bias can be confirmed further by calculation of the ratios of medians for males and females.</jats:sec

Proteomic Analyses Reveal High Expression of Decorin and Endoplasmin (HSP90B1) Are Associated with Breast Cancer Metastasis and Decreased Survival

BACKGROUND: Breast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample screening with mass spectrometry, as it allows direct comparison of protein expression between normal and pathological states. The purpose of this study was to use a systematic and objective method to identify biomarkers with possible prognostic value in breast cancer patients, particularly in identifying cases most likely to have lymph node metastasis and to validate their prognostic ability using breast cancer tissue microarrays. METHODS AND FINDINGS: Differential proteomic analyses were employed to identify candidate biomarkers in primary breast cancer patients. These analyses identified decorin (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour microenvironment and in pathways related to tumorigenesis. This study indicates that high expression of Decorin is associated with lymph node metastasis (p&lt;0.001), higher number of positive lymph nodes (p&lt;0.0001) and worse overall survival (p = 0.01). High expression of HSP90B1 is associated with distant metastasis (p&lt;0.0001) and decreased overall survival (p&lt;0.0001) these patients also appear to benefit significantly from hormonal treatment. CONCLUSIONS: Using quantitative proteomic profiling of primary breast cancers, two new promising prognostic and predictive markers were found to identify patients with worse survival. In addition HSP90B1 appears to identify a group of patients with distant metastasis with otherwise good prognostic features

Different percentages of false-positive results obtained using five methods for the calculation of reference change values based on simulated normal and ln-normal distributions of data

Background Reference change values provide objective tools to assess the significance of a change in two consecutive results for a biomarker from an individual. The reference change value calculation is based on the assumption that within-subject biological variation has random fluctuation around a homeostatic set point that follows a normal (Gaussian) distribution. This set point (or baseline in steady-state) should be estimated from a set of previous samples, but, in practice, decisions based on reference change value are often based on only two consecutive results. The original reference change value was based on standard deviations according to the assumption of normality, but was soon changed to coefficients of variation (CV) in the formula (reference change value = ± Z ċ 2½ ċ CV). Z is being dependent on the desired probability of significance, which also defines the percentages of false-positive results. The aim of this study was to investigate false-positive results using five different published methods for calculation of reference change value. Methods The five reference change value methods were examined using normally and ln-normally distributed simulated data. Results One method performed best in approaching the theoretical false-positive percentages on normally distributed data and another method performed best on ln-normally distributed data. The commonly used reference change value method based on two results (without use of estimated set point) performed worst both on normally distributed and ln-normally distributed data. Conclusions The optimal choice of method to calculate reference change value limits requires knowledge of the distribution of data (normal or ln-normal) and, if possible, knowledge of the homeostatic set point. </jats:sec