Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients

Study of the prognostic impact of multidrug resistance gene expression in the management of breast cancer in the context of adjuvant therapy. This study involved 171 patients treated by surgery, adjuvant chemotherapy±radiotherapy±hormonal therapy (mean follow-up: 55 months). We studied the expression of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised, semiquantitative rt–PCR method performed on frozen samples of breast cancer tissue. Patients were classified as presenting low or high levels of expression of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff–Bloom–Richardson (SBR) grade, age and hormonal status. The impact of gene expression levels on 5-year disease-free survival (DFS) and overall survival (OS) was studied by univariate and multivariate Cox analysis. No statistically significant correlation was demonstrated between MDR1, MRP1 and GSTP1 expressions. On univariate analysis, DFS was significantly decreased in a context of low GSTP1 expression (P=0.0005) and high SBR grade (P=0.003), size ⩾5 cm (P=0.038), high T stage (P=0.013), presence of intravascular embolus (P=0.034), and >3 N+ (P=0.05). On multivariate analysis, GSTP1 expression and the presence of ER remained independent prognostic factors for DFS. GSTP1 expression did not affect OS. The levels of MDR1 and MRP1 expression had no significant influence on DFS or OS. GSTP1 expression can be considered to be an independent prognostic factor for DFS in patients receiving adjuvant chemotherapy for breast cancer

Fractal Characteristics of May-Grünwald-Giemsa Stained Chromatin Are Independent Prognostic Factors for Survival in Multiple Myeloma

The use of computerized image analysis for the study of nuclear texture features has provided important prognostic information for several neoplasias. Recently fractal characteristics of the chromatin structure in routinely stained smears have shown to be independent prognostic factors in acute leukemia. In the present study we investigated the influence of the fractal dimension (FD) of chromatin on survival of patients with multiple myeloma.We analyzed 67 newly diagnosed patients from our Institution treated in the Brazilian Multiple Myeloma Study Group. Diagnostic work-up consisted of peripheral blood counts, bone marrow cytology, bone radiograms, serum biochemistry and cytogenetics. The International Staging System (ISS) was used. In every patient, at least 40 digital nuclear images from diagnostic May-Grünwald-Giemsa stained bone marrow smears were acquired and transformed into pseudo-3D images. FD was determined by the Minkowski-Bouligand method extended to three dimensions. Goodness-of-fit of FD was estimated by the R(2) values in the log-log plots. The influence of diagnostic features on overall survival was analyzed in Cox regressions. Patients that underwent autologous bone marrow transplantation were censored at the day of transplantation.Median age was 56 years. According to ISS, 14% of the patients were stage I, 39% were stage II and 47% were stage III. Additional features of a bad prognosis were observed in 46% of the cases. When stratifying for ISS, both FD and its goodness-of-fit were significant prognostic factors in univariate analyses. Patients with higher FD values or lower goodness-of-fit showed a worse outcome. In the multivariate Cox-regression, FD, R(2), and ISS stage entered the final model, which showed to be stable in a bootstrap resampling study.Fractal characteristics of the chromatin texture in routine cytological preparations revealed relevant prognostic information in patients with multiple myeloma

Quality control initiative on the evaluation of the dysmegakaryopoiesis in myeloid neoplasms: Difficulties in the assessment of dysplasia.

Evaluation of megakaryocyte morphology is difficult but can be essential for the diagnosis of myelodysplastic syndromes (MDS) and other myeloid neoplasms. We agreed upon descriptions and provided images of megakaryoblasts and of normal and dysplastic megakaryocytes, which were used as a basis for assessing the concordance of expert morphologists in their recognition. We showed a high rate of concordance for the recognition of micromegakaryocytes and confirmed their strong association with hematologic neoplasia, including MDS. Concordance was also found to be good for the recognition of multinucleated megakaryocytes, which showed a significant association with MDS. However cytoplasmic abnormalities were found not to be useful in MDS recognition. The occurrence of appreciable numbers of nonlobulated and hypolobulated megakaryocytes in individuals without a myeloid neoplasm was confirmed. We demonstrated that subjects without a myeloid neoplasm can have some megakaryocytes that are assessed as 'dysplastic' or 'possibly dysplastic' and that to avoid over diagnosis of dysplasia, 'possibly dysplastic' forms should be excluded from the count of dysplastic cells. Our results demonstrate that the nature as well as the presence of megakaryocyte dysplasia is important in the diagnosis of MDS; although evaluation of 30 megakaryocytes is strongly recommended, it may be possible to recognize diagnostically important dysplasia when fewer megakaryocytes are present but highly diagnostic forms are seen