Background:KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases.Methods:Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13.Results:KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation.Conclusion:We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6–98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0% 95% CI 0.7–4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

No abstract

No abstract

Purpose and Experimental Design: Loss of human leukocyte antigen (HLA) expression on tumor cells is frequent in diffuse large B-cell lymphoma (DLBCL) arising in immune-privileged sites, such as the testis and central nervous system, and is associated with small homozygous deletions of HLA-DQ/HLA-DR and larger hemizygous deletions of the MHC region. To better understand the significance of down-regulation of HLA class II expression in relation to the homozygous and hemizygous deletions, we analyzed global gene expression patterns in a series of 26 testicular DLBCL after characterization of these deletions. Results: Low levels of HLA-DR mRNA in whole testicular DLBCL samples were associated with a strong down-regulation of numerous immune-related genes specific for T cells, macrophages, antigen presentation and processing, lymphocyte activation, chemokines and chemokine receptors, and the complement system. The number of CD3 + tumor-infiltratingTcells was also significantly lower in low expressors of HLA-DR mRNA. Interestingly, hemizygous and homozygous deletions in the MHC region did not have any additional effect on global gene expression. Conclusion:In conclusion, we found that loss of HLA class II mRNA expression in testicular DLBCL is associated with a significant change in global gene expression patterns. This effect is independent of the mechanism causing the down-regulation of HLA class II genes in the lymphoma cells.Diffuse large B-cell lymphomas (DLBCL) are a heterogeneous group of non-Hodgkin's lymphomas, of which 40% present at extranodal sites. Many extranodal DLBCL behave clinically essentially different from nodal DLBCL. A subset of extranodal DLBCL arises in immune-privileged sites (IP-DLBCL), such as the central nervous system or the testis. Among the extranodal DLBCL, testicular DLBCL stand out with a characteristic high relapse rate to the central nervous system and contralateral testis (1) and a very poor prognosis. In addition, patients with a low-risk International Prognostic Index have a very poor outcome (2).We previously described the loss of HLA class I and II expression on tumor cells in >50% of the primary IP-DLBCL of the testis and central nervous system (3 -6). In both IP-DLBCL subtypes, small homozygous deletions affected the HLA-DR and HLA-DQ genes, whereas larger hemizygous deletions affected the whole MHC region, including class I and III regions, as well. The specificity of this down-regulation in testicular DLBCL was confirmed in a recent immunohistochemical study on a large series of primary extranodal DLBCL presenting at various sites (7). In another recent study on predominantly primary nodal (non-IP) DLBCL, Rimsza et al. (8) showed that loss of expression of HLA class II is highly discriminative for the clinical behavior of the disease and by far the most significant single prognostic factor. Furthermore, loss of HLA-DR expression correlated with a low number of CD8 + T cells, suggesting that a presumed loss of tumor surveillance may have a negative effect on pati...