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Current prostate cancer risk classifications rely on clinicopathological parameters resulting in uncertainties for prognostication. To improve individual risk stratification, we examined the predictive value of selected proteins with respect to tumor heterogeneity and genomic instability. We assessed the degree of genomic instability in 50 radical prostatectomy specimens by DNA-Image-Cytometry and evaluated protein expression in related 199 tissue-microarray (TMA) cores. Immunohistochemical data of SATB1, SPIN1, TPM4, VIME and TBB5 were correlated with the degree of genomic instability, established clinical risk factors and overall survival. Genomic instability was associated with a GS ≥ 7 (p = 0.001) and worse overall survival (p = 0.008). A positive SATB1 expression was associated with a GS ≤ 6 (p = 0.040), genomic stability (p = 0.027), and was a predictor for increased overall survival (p = 0.023). High expression of SPIN1 was also associated with longer overall survival (p = 0.048) and lower preoperative PSA-values (p = 0.047). The combination of SATB1 expression, genomic instability, and GS lead to a novel Prostate Cancer Prediction Score (PCP-Score) which outperforms the current D'Amico et al. stratification for predicting overall survival. Low SATB1 expression, genomic instability and GS ≥ 7 were identified as markers for poor prognosis. Their combination overcomes current clinical risk stratification regimes. [ABSTRACT FROM AUTHOR]

In this retrospective study, we analyzed the association between tumor budding and perineural invasion as well as their prognostic role in pancreatic ductal adenocarcinoma. A total of N = 119 patients resected for pancreatic ductal carcinoma from 1996 to 2015 were included. Clinical and standard histopathological parameters were retrieved from the patient's records. One representative hematoxylin and eosin section from the tumor region was examined for perineural invasion and tumor budding using light microscopy. Tumor budding was assessed independently using two different methods: in the first approach, the number of buds was counted over three fields of 0.237 mm2 at 40-fold magnification; in the second approach, tumor budding was quantified according to the recommendation of the International Tumor Budding Consensus Conference (ITBCC) over a field of 0.785 mm2 at 20-fold magnification. Linear and logistic regression was applied to delineate association between perineural invasion, tumor budding, and other parameters; Kaplan-Meier and Cox regression were used in the survival analysis. Regardless of the quantification approach, high tumor budding was a significant negative prognostic factor in the univariable Cox regression (> 5 buds/0.237 mm2, hazard ratio (HR) 1.66, 95% confidence interval (CI) 1.06-2.61, p = 0.027; ≥ 10 buds/0.785 mm2, HR 1.68, 95% CI 1.07-2.64, p = 0.024). In the multivariable model adjusting for stage and standard histopathological parameters, lymph vessel invasion (HR = 2.43, 95% CI 1.47-4.03, p = 0.001) and tumor budding > 5 buds/0.237 mm2 (HR = 1.70, 95% CI 1.07-2.7, p = 0.026) were independent negative prognostic factors, while adjuvant therapy was a positive prognostic factor (HR = 0.54, 95% CI 0.33-0.86, p = 0.009). No significant prognostic value could be delineated for perineural invasion. In conclusion, tumor budding is an independent negative prognostic factor in pancreatic ductal adenocarcinoma associated with lymph node metastasis. The prognostic role of perineural invasion remains uncertain. [ABSTRACT FROM AUTHOR]

Classical Hodgkin lymphoma is dominated by the non-neoplastic microenvironment, while the neoplastic Hodgkin-Reed-Sternberg cells compose only a minority of cells in the lymphoma tissue. Both the Hodgkin-Reed-Sternberg cells due to their expression of CD30 and PD-L1 and the microenvironment with abundant T cells and expression of PD1 are specifically targeted by new treatment concepts. We aimed to understand the dynamics of therapeutic targets in patients treated with conventional chemotherapy. We analyzed sequential biopsy specimens obtained at diagnosis and at relapse from the same patient for morphology, immunophenotype, and microenvironmental components. The morphological subtype changed between primary and relapse biopsy in 20% of cases. The immunophenotype was stable with respect to CD30, CD3, and LMP1 but variable with respect to CD15 and CD20 expression. Gene expression revealed 8 upregulated and 20 downregulated genes at relapse (p ≤ 0.05) with a consistent logarithmic fold change direction in at least 75% of all cases. For PD1, we found discrepant results between gene expression analysis (decrease at relapse) and number of PD1-positive cells assessed by immunohistochemistry (unchanged at relapse). PD-L1 in the neoplastic cells appeared unchanged between primary diagnosis and relapse. The expression of the therapeutic targets CD30, PD1, and PD-L1 can reliably be assessed in tumor specimen at first diagnosis and is unchanged under conventional chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The risk, prevention, and treatment of colorectal neoplasia in inflammatory bowel disease (IBD) are still a matter of debate. The aim of this study was to analyze the occurrence of colorectal neoplasia in IBD patients who underwent proctocolectomy. Methods: The study population comprised of 123 IBD patients who underwent proctocolectomy because of neoplasia, therapy refractivity, or complications between January 2000 and July 2011. Results: One hundred fourteen (92.7 %) patients were pre-operatively diagnosed with ulcerative colitis, 5 (4.1 %) with colitis indeterminata, and 4 (3.3 %) with colonic Crohn's disease. Colectomy was indicated in 39 (31.7 %) patients because of a neoplasia, in 68 (55.3 %) because of a refractory course of the disease, and in 16 (13.0 %) because of complications. Neoplasia was found in 36 patients on a histopathologic evaluation of the colectomy specimens. Ten (8.1 %) patients post-operatively showed a pre-operatively not described advanced neoplasia. In three (2.4 %) of these patients, the detection of advanced neoplasia (two high-grade intraepithelial neoplasias (IENs), one carcinoma) was a complete de novo finding. Carcinoma had not been diagnosed pre-operatively in six (4.9 %) patients. A multifocal distribution of neoplasia was seen in 66.7 % of patients with neoplasia. The median duration of disease was 15.5 years in case of neoplasia opposed to 6.0 years in those without neoplasia detection. Conclusion: Our data demonstrate a high rate of pre-operatively undetected high-grade IENs and carcinoma and a frequent multifocal occurrence in IBD patients with long-standing inflammation of the colon. This should be kept in mind for treatment decisions particularly in patients with a chronic refractory course of the disease. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine neoplasia (NEN) with unknown primary site (NEN-CUP tumors) may have a poor prognosis. We evaluated the clinical presentation, therapy, outcome, and risk factors for adverse outcomes in patients who had these tumors. Methods: In 243 patients who had NEN, a retrospective review was performed in 38 patients who had NEN-CUP tumors. The 38 patients who had NEN-CUP tumors were evaluated in three groups: group 1 (surgery; primary tumor detected; ten patients); group 2 (surgery; no primary tumor detected; ten patients); and group 3 (no surgery; 18 patients). Risk factors were evaluated with univariate and multivariate analyses. Results: Most patients who had NEN-CUP tumors [32 patients (84 %)] had World Health Organization (WHO) performance score of 0 or 1, and most tumors [24 patients (63 %)] were well differentiated (WHO grade, G1 or G2; Ki-67 index, ≤20 %). Univariate analysis showed that greater survival was significantly associated with lower patient age, lower WHO performance score, lower WHO grade, lower number of metastatic sites, treatment with surgery, and no treatment with chemotherapy. Multivariate analysis showed that low WHO performance score (hazard ratio 7.63, 95 % confidence interval (CI) 2.63-22.19) and treatment with surgery (hazard ratio 0.10, CI 0.028-0.381) were significant independent predictors of improved survival. Conclusions: In patients with NEN-CUP tumors, surgical treatment is an independent predictor of better survival. Therefore, surgical treatment may be indicated in patients with good general health status and well-differentiated NEN-CUP tumors. [ABSTRACT FROM AUTHOR]

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Purpose: Research projects and clinical trials strongly rely on high-quality biospecimens which are provided by biobanks. Since differences in sample processing and storage can strongly affect the outcome of such studies, standardization between biobanks is necessary to guarantee reliable results of large, multicenter studies. The German Cancer Aid Foundation (Deutsche Krebshilfe e.V.) has therefore initiated the priority program 'tumor tissue banks' in 2010 by funding four biobank networks focusing on central nervous system tumors, melanomas, breast carcinomas, and colorectal carcinomas. The latter one, the North German Tumor Bank of Colorectal Cancer ( ColoNet) is managed by surgeons, pathologists, gastroenterologists, oncologists, scientists, and medical computer scientists. Methods and results: The ColoNet consortium has developed and harmonized standard operating procedures concerning all biobanking aspects. Crucial steps for quality assurance have been implemented and resulted in certification according to DIN EN ISO 9001. A further achievement is the construction of a web-based database for exploring available samples. In addition, common scientific projects have been initiated. Thus, ColoNet's repository will be used for research projects in order to improve early diagnosis, therapy, follow-up, and prognosis of colorectal cancer patients. Apart from the routine sample storage at −170 °C, the tumor banks' unique characteristic is the participation of outpatient clinics and private practices to further expand the sample and clinical data collection. Conclusion: The first 2 years of funding by the German Cancer Aid Foundation have already led to a closer scientific connection between the participating institutions and to a substantial collection of biospecimens obtained under highly standardized conditions. [ABSTRACT FROM AUTHOR]

The mechanisms underlying the transformation from chronic Helicobacter pylori gastritis to gastric extranodal marginal zone lymphoma (MALT lymphoma) are poorly understood. This study aims to identify microRNAs that might be involved in the process of neoplastic transformation. We generated microRNA signatures by RT-PCR in 68 gastric biopsy samples representing normal mucosa, gastritis, suspicious lymphoid infiltrates, and overt MALT lymphoma according to Wotherspoon criteria. Analyses revealed a total of 41 microRNAs that were significantly upregulated ( n = 33) or downregulated ( n = 8) in succession from normal mucosa to gastritis and to MALT lymphoma. While some of these merely reflect the presence of lymphocytes (e.g. miR-566 and miR-212) or H. pylori infection (e.g. miR-155 and let7f), a distinct set of five microRNAs (miR-150, miR-550, miR-124a, miR-518b and miR-539) was shown to be differentially expressed in gastritis as opposed to MALT lymphoma. This differential expression might therefore indicate a central role of these microRNAs in the process of malignant transformation. [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dendritic cell neoplasms of the World Health Organization classification comprise Langerhans cell histiocytosis, Langerhans cell sarcoma, interdigitating dendritic cell sarcoma, follicular dendritic cell sarcoma, and dendritic cell sarcoma, not otherwise specified. Several studies based on immunohistochemical and ultrastructural analysis tried to further clarify the origin of these neoplasms which are thought to derive from mesenchymal or bone marrow precursors. Lymphatic vessel endothelium hyaluronan receptor-1 (LYVE-1) was recently described as a marker for lymphatic endothelium which is expressed on normal liver blood sinusoid lining cells, spleen endothelium, activated tissue macrophages, blood vessels in the lung, endothelial cells of lymphatic sinuses, and in fibroblastic reticular cells in lymph nodes. We present a case of LYVE-1-positive reticulum cell neoplasm in an axillary lymph node. To the best of our knowledge, there has been no report about LYVE-1 expression in histiocytic or dendritic cell neoplasms so far. Due to the assumed specificity of this antibody, we propose designation of this reticulum cell sarcoma as lymphatic sinus lining cell sarcoma which might finally represent another subtype of reticulum cell sarcomas. [ABSTRACT FROM AUTHOR]

Introduction: Tissue microarrays comprise numerous small representative tissue samples from hundreds of different cases assembled on a single histologic slide, and therefore allow high throughput analysis of multiple specimens at the same time. Mast cells are paracrine cells found ubiquitously in connective tissue. Expression of the serine proteases tryptase and chymase, as well as KIT protein, the receptor for stem cell factor (SCF), has been demonstrated in mast cells. Because little is known about the role of mast cells in the placenta, we investigated the number and expression of chymase, tryptase, and KIT protein in placental mast cells using newly developed tissue microarrays. Materials and methods: Tissue microarrays were prepared from archival paraffin tissue blocks of 90 placentae, including 15 normal ones as a control group. Gestational age of the placentae ranged from 7 to 42 weeks. Sections of formalin-fixed paraffin-embedded material were prepared on chemically activated cover-slides. The slides were cut in 4-mm² squares containing representative areas, and transferred to a tissue microarray. Hematoxylin and eosin (H&E), chloroacetate esterase (CAE), toluidine blue, periodic acid—Schiff (PAS), and immunohistochemical staining were performed. The number of mast cells and expression of chymase, tryptase, and KIT protein were evaluated in each case. Results: Mast cell numbers in placentae with inflammation/abortion exceeded that of normal placentae. Although statistically not significant, we furthermore observed an increase in chymase-positive mast cells in the group of placentae associated with fetal malformations/chromosomal aberrations compared with normal placentae. Discussion: Novel tissue microarray technique has been introduced into placental research, and allows multiple placental tissue samples to be effectively analyzed simultaneously. This study indicated an increased number of chymase-positive mast cells in placentae with fetal malformation/chromosomal aberration. Activation of angiotensin II by chymase may play a role in fetal malformation. Moreover, it has been speculated that mast cells may only express chymase (MCC). Our findings denote the presence of placental MCC. However, further studies are needed to elucidate more precisely the role of mast cell chymase in the placenta. [ABSTRACT FROM AUTHOR]

Umbilical anomalies are a rare presentation in fetal and neonatal period. We report a case of a patent urachus with an allantoic cyst diagnosed prenatally at 14 weeks of gestation and its spontaneous course throughout ongoing pregnancy. Thoroughly ultrasound examination enabled comprehensive counselling of the parents and together with pediatricians and pediatric surgeons determining the appropriate postnatal surgical management. [ABSTRACT FROM AUTHOR]

The article discusses research about the incidence of lymphoepithelial lesions (LEL) in gastrointestinal follicular lymphoma (GI-FL). It evaluated histomorphologically 31 cases of GI-FL and performed immunohistochemical stains for all cases. Results suggest that LELs might be quite different in GI-FL and that LELs are not exclusive to mucosa-associated Lymphoid Tissue (MALT) lymphomas.