Significance of ETV6 rearrangement in acute promyelocytic leukemia with t(15;17)/promyelocytic leukemia/retinoic acid receptor alpha.

Acute promyelocytic leukemia (APL) is a common subtype of acute myeloid leukemia in China. Since the application of arsenic trioxide and all-trans retinoic acid in the treatment of APL, the prognosis has greatly improved. However, ~20% of patients with APL relapse upon completing chemotherapy. Decreasing the relapse rate and incidence of early mortality may pose the greatest challenges for the future management of APL. Recently, Ets variant 6 (ETV6) was reported to be involved in a variety of translocations associated with hematological malignancies of myeloid and lymphoid origin. To date, little is known about the clinical implication of ETV6 rearrangement in APL. In the present study, ETV6 rearrangement was examined by split-signal fluorescence in situ hybridization in 258 adults with APL, and its association with the clinical features and outcomes of the patients was analyzed. The data suggested that ETV6 rearrangement may be an independent unfavorable prognostic factor for overall survival in APL patients.

Expression of SATB1 and HER2 in breast cancer and the correlations with clinicopathologic characteristics.

BACKGROUND: Special AT-rich sequence binding protein 1 (SATB1) is found acting as a "genome organizer" that functions as a landing platform to regulate tissue-specific gene ex-pression. In breast cancer cell lines it has been proven that SATB1 could upregulate the expression of the HER2. In this paper, the relevance of SATB1 and HER2 expression was assessed in human breast cancer tissues, and their influence on tumor histological grade and patients' survival was explored. METHODS: Using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), 169 patients with breast cancer were assessed for SATB1 expression, HER2 amplification and hormone-receptor (HR) expression. The effects of SATB1 expression on HER2 and HR expression as well as their association with clinicopathologic characteristics were further analyzed by statistical evaluation. RESULTS: SATB1 expression was correlated with HER2 expression in breast cancer(r = 0.191; p = 0.013). SATB1, HER2 and SATB1/HER2 co-expression was negatively correlated with HR expression (r = -0.228, p = 0.003; r = -0.338, p = 0.000; r = -0.527, p = 0.000, respectively). SATB1 and HER2 single positive and their co-expression were all significantly correlated with higher histological grade (r = 0.239, p = 0.002; r = 0.160, p = 0.038; r = 0.306, p = 0.003, respectively). Multivariate cox regression analyses showed that SATB1 and HER2 were independent risk factors for breast cancer patients, while HR was a protective factor for patients' survival. Comparing to SATB1 or HER2 single positive expression, SATB1/HER2 co-expression tended to have even worse prognosis. CONCLUSIONS: SATB1 and HER2 performed a synergistic effect in breast cancer. Their expression correlated with poorly differentiated breast cancer and indicated an unfavorable prognosis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1400555050159723 .

Evaluation of biomarker changes after administration of various neoadjuvant chemotherapies in breast cancer.

To assess the changes in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 expression in breast cancer patients after various neoadjuvant chemotherapies. Data from 138 locally advanced breast cancer patients with histological diagnoses were reviewed. Seventy patients (group 1) were given 4 cycles of 500 mg/m(2) cyclophosphamide and 50 mg/m(2) pirarubicin every 21 days. Sixty-eight patients (group 2) were given 4 cycles of 500 mg/m(2) cyclophosphamide and 75 mg/m(2) docetaxel every 21 days. The biomarker changes of the operated tumor tissues were compared with the initial core biopsies. ER, PR, HER2 and Ki-67 expression changed by 28.6%, 22.9%, 17.1% and 54.3%, respectively, after neoadjuvant chemotherapy in group 1 and 16.2%, 22.1%, 13.2% and 70.6%, respectively, after neoadjuvant chemotherapy in group 2. There were significant differences between the groups regarding ER and Ki-67 status changes, and these changes can be used to inform treatment strategies.

[Polymorphic analysis of 5 Y-SNP loci in Han population of Jinan].

OBJECTIVE: To investigate polymorphism distribution of the 5 Y-SNP loci in Jinan Han population, and evaluate their potential in forensic application. METHODS: Genotyping of 5 Y-SNP loci (M89, M9, M122, M134, M95) were executed in the sample of 103 unrelated Chinese male individuals in Jinan Han population by using fragment length discrepant allele specific PCR (FLDAS-PCR). RESULTS: In 5 Y-SNP loci, genetic polymorphism were identified in Jinan Han population, and the ranges of gene diversity(GD) were 0.093 3-0.491 2. Twenty different haplotypes were observed and the haplotypes diversity (HD) was 0.867 9. Six different haplogroups were detected according to international association of Y chromosome nomenclature. CONCLUSION: Five Y-SNP loci and their haplogroups in Jinan Han population are highly polymorphic, which can provide more information for the genetic structure analysis and forensic genetics research in the region.

[Analysis and clinical significance of ETV6 rearrangement in myelodysplastic syndromes patients].

OBJECTIVE: To identify the ETV6 gene rearrangement in patients with myelodysplastic syndromes (MDS) and explore its relationship with prognosis and disease stages. METHODS: ETV6 rearrangement in 58 MDS cases were detected by conventional cytogenetics and Split-signal FISH. RT-PCR was used to detect 9p24-12p13 balance translocation with special designed primers ETV6F1/F2 and JAK2R1/R2. The relationship between ETV6 rearrangement and prognosis and disease staging in MDS patients was analyzed. RESULTS: ETV6 rearrangement were found in 4 (6.9%) of 58 cases, among which ETV6/JAK2 fusion was identified by RT-PCR in 1 (1.7%) case. The mean follow-up duration was 12 months. All 4 patients (100%) with rearrangement transformed into acute leukemia, with a median survival time (MS) of 7 months; while 10 patients (17%) in the non-translocation group transformed to acute leukemia, with a MS of 28 months. In addition, all 4 patients (100%) with rearrangement were in advanced stage of MDS( RAEB), while 17 cases (31.5%) in non-rearrangement group were in that stage. CONCLUSIONS: ETV6 rearrangement has higher expression rate (6.9%), and is closely associated with disease stage and prognosis in MDS.

[Preliminary study of multivariable model in predicting response to immunosuppressive therapy in patients with aplastic anemia].

OBJECTIVE: To evaluate the potential usefulness of a multivariable model in predicting the response to immunosuppressive therapy (IST) in patients with aplastic anemia (AA), and its application to the clinical practice. METHODS: PB T cells subpopulation and BM T cells intracellular IFN-gamma and IL-4 were serially analyzed by flow cytometry (FCM) before and during treatment. HLA-DRB1 * 1501 phenotype was analyzed by PCR-SSP. The predictive potentials of different parameter combinations for clinical responsiveness were statistically assessed. RESULTS: In all evaluated parameters, CD8+ cell intracellular IFN-gamma had the relatively best diagnostic value with sensitivity and specificity of 94.3% and 62.5%, and positive and negative predictive value of 84.6% and 83.3% respectively. Positive CD8+ cell intracellular IFN-gamma plus Tc1/Tc2 < 50 could increase the positive predictive value to 92.3%. A multivariable model consisting of absolute neutrophil count (ANC), BM T cell intracellular IFN-gamma, Tc1/Tc2 ratio and HLA-DRB * 1501 phenotype of the patients was finally established. CONCLUSION: The multivariable model is superior to each of the single parameters in terms of predictive power of IST therapeutic outcome, and its higher accuracy and the clinical application make it potentially useful in practice.

[Clinical implications of combined measurement bone marrow T cells intracellular IFNgamma and HLA-DRB1*1501 measurement in predicting the response to immunosuppressive therapy for aplastic anemia].

OBJECTIVE: To evaluate the clinical implication of combined measurement of bone marrow (BM) T lymphocyte intracellular IFNgamma with HLA-DRB1*1501 in predicting the response to immunosuppressive therapy (IST) in patients with aplastic anemia (AA). METHODS: Enrolled into the present study were 51 idiopathic AA patients treated with cyclosporine A (CsA) based IST. BM CD(8)(+) T lymphocyte intracellular IFNgamma was determined with flow cytometry and HLA-DRB1*1501 detected with PCR-sequence specific primer before treatment. The relationship between laboratory indices and clinical response were investigated and the potential usefulness of parameters in predicting the response to IST for AA was evaluated. RESULTS: These HLA-DRB1*1501 shows sensitivity of 45.7% (16/35) and specificity of 87.5% (14/16) respectively. Intracellular IFNgamma has sensitivity of 94.3% (33/35) and specificity of 62.5% (10/16), respectively. With combination of intracellular IFNgamma with HLA-DRB1*1501, the parallel test increases the sensitivity of 97.1% (34/35) and the negative predictive value of 90.0% (9/10). On the other hand, the serial test improves the specificity and positive predictive value which both achieve 93.7% (15/16). It could be calculated through a logistic regression equation that the probabilities of prediction of four subgroups of patients whose results are both positive reaction, a positive intracellular IFNgamma plus negative HLA-DRB1*1501, a negative intracellular IFNgamma plus positive HLA-DRB1*1501 and both negative reaction are 89.0%, 77.4%, 34.5% and 18.2%, respectively. CONCLUSIONS: Combination of BM T cells intracellular IFNgamma stain and HLA-DRB1*1501 phenotype can be a useful predictor for AA patients in immunosuppressive therapy. The patients with both positive results of the two tests may have more possibilities to response to IST. It may have an important implication for the majority of AA patients whose intracellular IFNgamma stain has a positive reaction.