ERG expression in multiple myeloma-A potential diagnostic pitfall.

INTRODUCTION: ERG expression has been described as a frequent event in prostate cancer indicating poor prognosis and promoting oncogenesis. It has also been demonstrated in Ewing's sarcoma, acute myeloid leukemia and acute T-lymphoblastic leukemia but could not be found in other epithelial tumors, Hodgkin's or Non-Hodgkin's lymphoma. We aimed to analyze ERG expression in multiple myeloma, following an index case of a patient with metastases of unknown origin in the spine strongly expressing ERG, which were thought to be of prostatic origin but turned out to be plasmacytic lesions. MATERIAL AND METHODS: We subsequently selected 12 formalin-fixed, paraffin-embedded tissue samples of multiple myeloma from our archives and performed immunohistochemical staining for ERG. RESULTS: All 12 analyzed cases showed strong nuclear expression of ERG in >90% of tumor cells (myeloma cells). CONCLUSIONS: This report highlights a potential and critical diagnostic pitfall in biopsy specimens where morphology is only of limited assistance in reaching the correct diagnosis. It urges pathologists to exercise caution in cases where strong ERG-positivity implicates the presence of a prostatic neoplasia and illustrates the need for further immunohistochemical examination.

Expression of cyclooxygenase-2 has no impact on survival in adenocarcinoma of the esophagogastric junction but is associated with favourable clinicopathologic features.

BACKGROUND: COX-2 expression induces carcinogenesis and is thought to be an adverse prognostic factor in gastric carcinomas while the prognostic value of DNA mismatch repair (MMR) is still controversial. Concerning adenocarcinomas of the esophagogastric junction, no comprehensive data regarding either factors are available as of yet. OBJECTIVE: We assessed expression of COX-2, MLH1 and MSH2 in adenocarcinoma of the esophagogastric junction in relation to patients' survival and various clinicopathologic features. DESIGN: Immunohistochemical studies (using antibodies against COX-2, MLH1 and MSH2) were performed in a study population of 228 tumours. Follow-up data was available for all patients with a mean follow-up time of 42.8 months. RESULTS: 78 (34.2%) tumours were COX-2 negative, 148 (64.9%) showed COX-2 positivity. Assessment of COX-2 expression and clinicopathologic features revealed an inverse correlation with depth of tumour invasion and number of metastatic lymph nodes (p=0,021 and p=0,004, respectively). No correlation with other features could be demonstrated. 62 cases (27.2%) showed loss of DNA repair enzymes MLH1 and/or MSH2. MMR differed significantly between COX-2 positive and negative cases (p=0,028). Kaplan-Meier survival analyses revealed no impact on patients' survival for COX-2 expression or MMR status (p=0.837 and p=0.972, respectively). CONCLUSIONS: Expression of COX-2 in adenocarcinomas of the esophagogastric junction seems to have no prognostic effect or impact on patients' survival but is associated with favourable clinicopathologic factors. MMR deficiency was more frequent in COX-2 negative tumours, but MMR status had no impact on survival and patients' outcome whatsoever.

High Density of Tumor-infiltrating B-Lymphocytes and Plasma Cells Signifies Prolonged Overall Survival in Adenocarcinoma of the Esophagogastric Junction.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have been shown to be of prognostic significance in a variety of tumors. Not only T-cell, but also B-cell infiltration is commonly associated with improved survival. MATERIALS AND METHODS: We assessed the density of tumor-infiltrating B-cells, as well as that of plasma cells, in 210 adenocarcinomas of the esophagogastric junction through immunohistochemical analysis using antibodies against CD20 and CD138. RESULTS: No correlation between density of B-cells or plasma cells and various clinicopathologic features could be established. High density of tumor-infiltrating B-cells, as well as plasma cells, showed significantly better overall survival (OS) compared to patients with no infiltrates (p=0.047 and p=0.022, respectively). Cox proportional hazard analysis could verify B-cell infiltration as an independent prognostic factor (hazard ratio (HR)=0.683; 95% confidence interval (CI)=0.517-0.901; p=0.007). CONCLUSION: Plasma cell and B-cell infiltration correlates with prolonged OS and might identify a patient subset with favorable disease course.

Evaluation of general and coronary atherosclerosis and malignant disease demonstrates inverse correlations for specific cancer types as well as cancer in general.

CONTEXT: Historical data has shown that cancer in general has been associated with less atherosclerosis while recently several studies have demonstrated more heterogeneous relations. However, most investigations were carried out clinically or radiographically and updated exhaustive, comprehensive autopsy studies are lacking. In our study, we aimed to assess the relationship between malignancy and grade of atherosclerosis in different locations (general, coronary) in a large study population over the course of 14 years. METHODS: 2370 patients (autopsy reports) were analyzed retrospectively in regard to various parameters including demographics, organ weights, distribution and severity of atherosclerosis and presence or absence of malignancy. RESULTS: Our study shows that malignant disease is usually associated with less general and coronary atherosclerosis (p=0.002 and p<0.001). Especially breast, colorectal and pancreatic cancer as well as lymphomas/lymphoid leukaemia and sarcomas were associated with significantly less general and coronary AS (p-values<0.001-0.031). In addition, a positive correlation between coronary atherosclerosis and heart weight could be detected (ρ=0.302, p<0.001). As a common observation, male sex was associated with increased severity of general and coronary atherosclerosis in both cancer and non-cancer groups (p<0.001). CONCLUSIONS: We demonstrated that an inverse correlation between atherosclerosis and cancer in general is still sound today despite tremendous changes and advances in therapy strategies and diagnostics. Additionally, we could highlight that the effect was most pronounced in breast, colorectal and pancreatic cancer, sarcomas and lymphomas/lymphoid leukaemia.

Dysregulation of microRNAs in angioimmunoblastic T-cell lymphoma.

BACKGROUND: Angioimmunoblastic T-cell lymphomas (AITLs) are the second most frequent peripheral T-cell lymphomas in humans worldwide and histomorphologically well characterized. MicroRNAs are a group of small non-coding RNAs that can negatively regulate gene expression on a posttranscriptional level. Their dysregulation has been shown to be of importance in numerous tumour entities. MATERIALS AND METHODS: As a first step towards understanding the possible influence of microRNA-dysregulation in AITL, we analyzed the expression signatures of 760 microRNAs in 30 nodal AITLs in comparison to reactive lymphadenitis with T-zone hyperplasia. RESULTS: We found miR-34a, miR-146a and miR-193b to be up-regulated, as well as miR-140-3p, let-7g, miR-30b and miR-664 to be down-regulated in AITL to a significant level. CONCLUSION: The microRNA-signatures of AITL reveal some overlap to autoimmune diseases, virus-triggered lymphomas and angiogenic factors that, coupled with future studies, will potentially provide better understanding of this disease.

Oncogenic mutations and chromosomal aberrations in primary extranodal diffuse large B-cell lymphomas of the thyroid--a study of 21 cases.

CONTEXT: Primary extranodal diffuse large B-cell lymphomas of the thyroid (ptDLBCL) constitute a rare entity, which until now was not fully explored. OBJECTIVE: Due to recently published data genetically linking ptDLBCL to a subset of thyroid carcinoma, we assessed the occurrence of oncogenic mutations and copy number alterations. DESIGN: A high-resolution array-based comparative genomic hybridization approach was applied to quantify genomic aberrations in a study population of 21 ptDLBCL patients. In addition, we investigated the frequency of mutations involving the BRAF, NRAS, and MYD88 genes in correlation with immunohistochemical data. RESULTS: Chromosomal gains were recurrently detected at 6p21.33-p21.31, 6p22.2, 12p13.31, 14q31.1, 14q32.33, 19p13.3, and 22q11.22; numeric losses were most frequently observed at 6p21.3-p21.31, 10q26.3, 19p13.3, 20q13.33, and 21q11.2. Aberrations affecting 6p22.2 and 14q32.33 as well as 22q11.22 differed slightly between germinal center B-cell (GCB) and non-GCB groups. Statistically significant deviations were detected at 20q13.33 and 21q11.2. These specific alterations do not seem to occur in thyroid carcinomas or other DLBCL, according to previously published literature. Analysis of BRAF and NRAS showed mutation frequencies of 4.8 and 9.5%, respectively. No MYD88 mutations could be detected in any of the analyzed cases. Fluorescence in situ hybridization demonstrated breakage events involving the BCL2, BCL6, and cMYC locus in 14.3, 9.5, and 9.5%, respectively. CONCLUSIONS: Our study revealed ptDLBCL to be predominantly composed of the GCB type, harboring no MYD88 mutations and showing infrequent mutations in the BRAF and NRAS genes. Additionally, array comparative genomic hybridization showed no overlapping alterations between ptDLBCL and thyroid carcinomas or other nodal or extranodal DLBCL.