Interlaboratory reproducibility of semiautomated cell cycle analysis of flow cytometry DNA-histograms obtained from fresh material of 1,295 breast cancer cases.

Conflicting prognostic results have been published as to the DNA variables, such as DNA ploidy, DNA index, and % S-phase cells for breast cancer patients. These variables can be obtained by interpreting DNA histograms by cell cycle analysis. Explanations for these conflicting results might be found on the level of the interpretation of the DNA histograms. In a previous study, the semi automated cell cycle analysis computer program MultiCycle (Phoenix Flow Systems, San Diego, CA) showed high intralaboratory reproducibility. However, what types of DNA histograms may cause disagreements was still unclear. The aim of this study was to determine the interlaboratory reproducibility of MultiCycle-based cell cycle analysis of 1,295 flow cytometric DNA histograms derived from fresh frozen breast cancer material and to clarify potential sources of interobserver variation when analyzing DNA histograms. DNA ploidy classification into diploid, hyperdiploid, tetraploid, hypertetraploid, and multiploid showed an interlaboratory agreement of 94% (kappa value = 0.92). The 6% discrepancies (n = 74) were caused by tetraploid peaks, as established in one laboratory, which shifted outside the tetraploid region on reanalysis by the other laboratory (37%), shoulders sometimes interpreted as peaks (24%), small peaks not always recognized as such (24%), fitting failures (10%), and overlooking of tetraploid peaks (5%). Furthermore, the cell cycle analysis variables showed variable reproducibility. The % S-phase cells of the first, second, and third cell cycle showed overall a moderate reproducibility (0.62 or = 0.94), and the % G2/M-phase cells of the first, second, and third cell cycle were poorly reproducible (0.22 < or = R < or = 0.68). When a cut-point was used at the mean value of 7% for the average % S-phase cells, the number of "threshold discrepancy cases" was 6%. Sources of variation for cell cycle analysis were variations in the debris correction procedures, disagreement about the modes of the aneuploid peaks, disagreement about small peaks, shoulders sometimes interpreted as peaks, and overlooking of tetraploid peaks

Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years.

Item does not contain fulltextPURPOSE: To validate the independent strong prognostic value of mitotic activity index (MAI) in lymph node (LN) -negative invasive breast cancer patients younger than 55 years in a nationwide multicenter prospective study. PATIENTS AND METHODS: Analysis of routinely assessed MAI and other prognosticators in 516 patients (median follow-up, 118 months; range, 8 to 185 months), without systemic adjuvant therapy or previous malignancies. RESULTS: Distant metastases occurred in 127 patients (24.6%); 90 (17.4%) died as a result of metastases. MAI ( or = 10) showed strong association with recurrence (hazard ratio [HR], 3.12; 95% CI, 2.17 to 4.50; P or = 10. This effect was independent of age, estrogen receptor (ER) status, and tumor diameter (which were significant prognosticators). In multivariate analysis with regard to patient age, tumor diameter, grade, ER status, and the St Gallen criterion, MAI proved to be an independent and the strongest prognosticator. Tubular formation (TF) and nuclear atypia (NA), as constituents of (expert revised) grade, had no (for TF) or limited (for NA, P = .048) additional prognostic value to the MAI. In the group with MAI less than 10, MAI less than 3 versus more than 3 had additional value but the classical threshold of 0 to 5 v 6 to 10 did not. With this additional subdivision of MAI as less than 3, 3 to 9, and more than 9, NA lost its additive prognostic value. CONCLUSION: The MAI is the strongest, most widely available, easily assessable, inexpensive, well-reproducible prognosticator and is well suited to routinely differentiate between high- and low-risk LN-negative breast cancer patients younger than 55 years

Assessment of HER2 status in breast cancer biopsies is not affected by accelerated tissue processing

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The prognostic value of proliferation in lymph-node-negative breast cancer patients is age dependent.

Item does not contain fulltextIn lymph-node-negative invasive breast cancer patients70 years) without systemic adjuvant therapy and long follow-up (median: 108 months). The MAI decreases with age and the prognostic value of MAI varied by age group. For patientsor=10 versus<10 for MFS and OS were 3.1 and 4.4, respectively (P<.0001 for both), but only 1.9 and 1.9 (P=.004 and .006) for patients aged 55-70 years, while over 70 years, MAI was not significant (P=.11). The prognostic value of proliferation was age-dependent. Prognostic breast cancer studies must clearly indicate the age group being studied

Serum CA-125 in relation to adnexal dysplasia and cancer in women at hereditary high risk of ovarian cancer

Purpose: Serum CA-125 level is commonly used as indicator for ovarian cancer recurrence. However, its value for the prediction of neoplastic lesions is unknown. The aim of this study was to investigate whether CA-125 concentrations are indicative of adnexal dysplasia and cancer in women at hereditary high risk of ovarian/tubal cancer. Patients and Methods: CA-125 was obtained from 424 women at hereditary high risk of ovarian/tubal cancer attending the VU University Medical Center (Amsterdam, the Netherlands) between 1993 and 2005. Serum samples obtained at the second-to-last (n = 64) and last (n = 98) visit before surgery were tested in women who underwent adnexal surgery for diagnostic (n = 9) or prophylactic (n = 89) reasons. Serum samples obtained from 370 age-matched healthy women were used as controls. Results: Both the absolute value (P < .0001) and the serial change (P < .0001) of CA-125 were predictive for ovarian cancer (n = 8). For adnexal dysplasia (n = 23), the absolute value of CA-125 (P = .003) was predictive, but the serial change in CA-125 was not (P = .32). The odds ratio for adnexal dysplasia versus nondysplasia in the highest tertile (CA-125 levels ≥ 14 U/mL) compared with the lowest tertile (CA-125 < 10 U/mL) was 6 (95% CI, 1.32 to 36.66). Conclusion: In patients at hereditary high risk for adnexal cancer, both the absolute value of serum CA-125 and the change in serial CA-125 are predictors for ovarian cancer. Remarkably, the absolute value of CA-125 is also predictive for adnexal dysplasia. CA-125 values should, therefore, be taken into account in the decision toward prophylactic bilateral salpingo-oophorectomy