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2.
Breast Cancer Res Treat ; 152(2): 247-52, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26041687

ABSTRACT

Assessing hormone receptor status is an essential part of the breast cancer diagnosis, as this biomarker greatly predicts response to hormonal treatment strategies. As such, hormone receptor testing laboratories are strongly encouraged to participate in external quality control schemes to achieve optimization of their immunohistochemical assays. Nine Dutch pathology departments provided tissue blocks containing invasive breast cancers which were all previously tested for estrogen receptor and/or progesterone receptor expression during routine practice. From these tissue blocks, tissue microarrays were constructed and tested for hormone receptor expression. When a discordant result was found between the local and TMA result, the original testing slide was revised and staining was repeated on a whole-tissue block. Sensitivity and specificity of individual laboratories for testing estrogen receptor expression were high, with an overall sensitivity and specificity [corrected] of 99.7 and 95.4%, respectively. Overall sensitivity and specificity of progesterone receptor testing were 94.8 and 92.6%, respectively. Out of 96 discordant cases, 36 cases would have been concordant if the recommended cut-off value of 1% instead of 10% was followed. Overall sensitivity and specificity of estrogen and progesterone receptor testing were high among participating laboratories. Continued enrollment of laboratories into quality control schemes is essential for achieving and maintaining the highest standard of care for breast cancer patients.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Tissue Array Analysis/methods , Female , Humans , Quality Assurance, Health Care , Reproducibility of Results , Sensitivity and Specificity , Tissue Array Analysis/standards
3.
Hum Immunol ; 67(4-5): 303-10, 2006.
Article in English | MEDLINE | ID: mdl-16720210

ABSTRACT

Several risk factors including immune deficiencies, infections, and autoimmune diseases have been established for non-Hodgkin's lymphoma (NHL). For diffuse large B cell lymphoma (DLBCL), the most common type of lymphoma, no risk factors have been described, which may be due to the intrinsic heterogeneity of this disorder. Previously we reported that, in contrast to nodal DLBCLs, the majority of testicular DLBCLs manifested complete loss of HLA-DR and -DQ expression associated with homozygous deletions of the corresponding genes. To determine the correlation between HLA class II polymorphisms and these lymphomas, we applied DNA typing for HLA-DRB1 and HLA-DQB1 on 50 Dutch patients with testicular and 48 with nodal DLBCL and compared the frequencies with a cohort of healthy Dutch controls. Both the patients with nodal and those with testicular DLBCL manifested significantly higher frequencies of HLA-DRB1*15 than the controls (p < 0.018, odds ratio 2.09 and p < 0.013, odds ratio 2.12, respectively). Moreover, a positive association was seen with HLA-DRB1*12 (p = 0.043, odds ratio 4.17) in the patients with testicular DLBCL, and a negative association was seen with HLA-DRB1*07 (p = 0.022, odds ratio 0.13) in the patients with nodal DLBCL. Homozygous deletions of the HLA-DR/DQ region, evaluated by interphase fluorescence in situ hybridization were seen in 20 of 48 testicular tumors. No preferential loss or retention of a particular HLA-DR or -DQ allele was seen because all alleles were at least once retained or involved in a homozygous deletion.


Subject(s)
HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Histocompatibility Antigens Class II/genetics , Lymphoma, B-Cell/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Testicular Neoplasms/genetics , Gene Frequency , HLA-DQ beta-Chains , HLA-DRB1 Chains , Humans , Male , Netherlands , Polymorphism, Genetic , Sequence Deletion
4.
Blood ; 96(10): 3569-77, 2000 Nov 15.
Article in English | MEDLINE | ID: mdl-11071656

ABSTRACT

In B-cell lymphomas, loss of human leukocyte antigen (HLA) class I and II molecules might contribute to immune escape from CD8(+) and CD4(+) cytotoxic T cells, especially because B cells can present their own idiotype. Loss of HLA expression and the possible underlying genomic alterations were studied in 28 testicular, 11 central nervous system, and 21 nodal diffuse large B-cell lymphomas (DLCLs), the first two sites are considered as immune-privileged sites. The analysis included immunohistochemistry, loss of heterozygosity analysis, and fluorescent in situ hybridization (FISH) on interphase cells and isolated DNA fibers. Total loss of HLA-A expression was found in 60% of the extranodal cases and in 10% of the nodal cases (P <.01), whereas loss of HLA-DR expression was found in 56% and 5%, respectively (P <.01). This was accompanied by extensive loss of heterozygosity within the HLA region in the extranodal DLCLs. In 3 cases, retention of heterozygosity for D6S1666 in the class II region suggested a homozygous deletion. This finding was confirmed by interphase FISH that showed homozygous deletions in the class II genes in 11 of the 18 extranodal lymphomas but in none of the 7 nodal DLCLs (P <.001). Mapping by fiber FISH showed variable deletions that always included HLA-DQ and HLA-DR genes. Hemizygous deletions and mitotic recombinations often involving all HLA genes were found in 13 of 18 extranodal and 2 of 7 nodal lymphomas. In conclusion, a structural loss of HLA class I and II expression might help the B-cell lymphoma cells to escape from immune attack.


Subject(s)
Gene Deletion , Genes, MHC Class II/genetics , Lymphoma, B-Cell/genetics , Major Histocompatibility Complex/genetics , Adolescent , Adult , Aged , Central Nervous System Neoplasms/genetics , Central Nervous System Neoplasms/immunology , Central Nervous System Neoplasms/metabolism , Chromosome Mapping , Chromosomes, Human, Pair 6/genetics , Cytogenetic Analysis , Female , Genes, MHC Class II/immunology , HLA-A Antigens/genetics , HLA-A Antigens/metabolism , HLA-DQ Antigens/genetics , HLA-DQ Antigens/metabolism , HLA-DR Antigens/genetics , HLA-DR Antigens/metabolism , Homozygote , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Loss of Heterozygosity , Lymph Nodes/pathology , Lymphoma, B-Cell/immunology , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/metabolism , Major Histocompatibility Complex/immunology , Male , Middle Aged , Testicular Neoplasms/genetics , Testicular Neoplasms/immunology , Testicular Neoplasms/metabolism
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