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Egevad L, Ahmad A S, Algaba F, Berney D M, Boccon-Gibod L, Comperat E, Evans A J, Griffiths D, Grobholz R, Kristiansen G, Langner C, Lopez-Beltran A, Montironi R, Moss S, Oliveira P, Vainer B, Varma M & Camparo P (2013) Histopathology 62, 247-256 Standardization of Gleason grading among 337 European pathologists Aims: The 2005 International Society of Urological Pathology (ISUP) modification of Gleason grading recommended that the highest grade should always be included in the Gleason score (GS) in prostate biopsies. We analysed the impact of this recommendation on reporting of GS 6 versus 7. Methods and results: Fifteen expert uropathologists reached two-thirds consensus on 15 prostate biopsies with GS 67 cancer. Eighty-five microphotographs were graded by 337 of 617 members of the European Network of Uropathology (ENUP), representing 19 countries. There was agreement between expert and majority member GS in 12 of 15 cases, while members upgraded in three cases. Among members and the expert consensus, a GS >6 was assigned by 64.5% and 60%, respectively. Mean member GS was higher than consensus GS in nine of 15 cases. A Gleason pattern (GP) 5 was reported by 0.35.6% in 10 cases. Agreement between consensus and member GS was 58.289.3% (mean 71.4%) in GS 6 cases and 46.363.8% (mean 56.4%) in GS 7 cases (P = 0.009). Conclusions: While undergrading of prostate cancer used to be prevalent, some now tend to overgrade. Minimum diagnostic criteria for GP 4 and 5 in biopsies need to be better defined. Image libraries reviewed by experts may be useful for standardization.

Primary melanocytic tumours are uncommon neoplasms of the central nervous system. Although similarities with uveal melanomas have been hypothesized, data on their molecular features are limited.In this study, we investigated the mutational status of BRAF(V600E) , KIT, GNAQ, GNA11, N-RAS and H-RAS in a series of 19 primary melanocytic tumours of the central nervous system (CNS).We identified six cases harbouring mutations in the hotspot codon 209 of the GNAQ gene and two cases with mutations in the hotspot codon 209 of the GNA11 gene. Two mutations in codon 61 of N-RAS were also found. In the single strand conformation polymorphism (SSCP) analysis, no shifts corresponding to BRAF(V600E) mutations or suggesting activating mutations in the KIT gene were observed.In primary melanocytic tumours of the CNS, GNA11 and N-RAS mutations represent a mechanism of MAPK pathway activation alternative to the common GNAQ mutations. On the other hand, BRAF(V600E) mutations and activating KIT mutations seem to be absent or very rare in these tumours.

Whole slide imaging (WSI) has been used in conjunction with virtual microscopy (VM) for training or proficiency testing purposes, multicentre research, remote frozen section diagnosis and to seek specialist second opinion in a number of organ systems. The feasibility of using WSI/VM for routine surgical pathology reporting has also been explored. In this review, we discuss the utility and limitations of WSI/VM technology in the histological assessment of specimens from the prostate. Features of WSI/VM that are particularly well suited to assessment of prostate pathology include the ability to examine images at different magnifications as well as to view histology and immunohistochemistry side-by-side on the screen. Use of WSI/VM would also solve the difficulty in obtaining multiple identical copies of small lesions in prostate biopsies for teaching and proficiency testing. It would also permit annotation of the virtual slides, and has been used in a study of inter-observer variation of Gleason grading to facilitate precise identification of the foci on which grading decisions had been based. However, the large number of sections examined from each set of prostate biopsies would greatly increase time required for scanning as well as the size of the digital file, and would also be an issue if digital archiving of prostate biopsies is contemplated. Z-scanning of glass slides, a process that increases scanning time and file size would be required to permit focusing a virtual slide up and down to assess subtle nuclear features such as nucleolar prominence. The common use of large blocks to process prostatectomy specimens would also be an issue, as few currently available scanners can scan such blocks. A major component of proficiency testing of prostate biopsy assessment involves screening of the cores to detect small atypical foci. However, screening virtual slides of wavy fragmented prostate cores using a computer mouse aided by an overview image is very different from screening glass slides using a microscope stage. Hence, it may be more appropriate in this setting to mark the lesional area and focus only on the interpretation component of competency testing. Other issues limiting the use of digital pathology in prostate pathology include the cost of high quality slide scanners for WSI and high resolution monitors for VM as well as the requirement for fast Internet connection as even a subtle delay in presentation of images on the screen may be very disturbing for a pathologist used to the rapid viewing of glass slides under a microscope. However, these problems are likely to be overcome by technological advances in the future.

Einleitung: Die Prognose des duktalen Pankreaskarzinoms (PaCa) bleibt schlecht. Die Standardtherapie stellt die potentiell kurative Resektion mit nachfolgender adjuvanter Chemotherapie dar. Eine zuverlässige Vorhersage des Überlebens wie auch des Ansprechens auf eine adjuvante Therapie könnte[for full text, please go to the a.m. URL], 128. Kongress der Deutschen Gesellschaft für Chirurgie

In this study we aimed to evaluate the protein expression of class I histone deacetylases (HDAC) in testicular germ cell tumours (GCT) and to analyse differences between the histological subtypes of testicular GCT. 325 testicular GCT were included in a tissue microarray with each histological subtype of the tumour being separately represented on this array. Expression of class I HDAC isoforms 1, 2 and 3 was assessed by immunohistochemistry. While HDAC2 and 3 were highly expressed in all histological subtypes of GCT, HDAC1 was almost consistently expressed at lower levels. We observed significant differences in the expression of the respective HDACs between seminoma and non-seminoma GCT tissue components. Interestingly, choriocarcinomas showed generally high expression values for all three class I HDAC isoforms. Relevant correlations with clinicopathological parameters could not be demonstrated. Contrasting published findings on other tumour entities, no immediate practical diagnostic or prognostic value for HDAC1-3 in GCT could be inferred. However, the high expression levels might still be indicative for a treatment response to HDAC inhibitors which ought to be evaluated in further studies.

Einleitung: Matrix-Metalloproteinasen 2- und 9 (MMP-2,MMMP-9) sind an der Degradierung der Basalmembran beteiligt. Wir beobachteten, dass eine fischölreiche Omega-3-Fettsäure-haltige Diät den histologischen Schweregrad der akuten Pankreatitis (AP) vermindert. Daher untersuchten wir nun,[for full text, please go to the a.m. URL], 127. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: In einer vorhergehenden Studie haben wir nach 24 Stunden (h) unter einer parenteralen Ernährung mit Omega-3-Fettsäuren (Fischöl) eine Verminderung des histopathologischen Schweregrades der akuten nekrotisierenden Pankreatitis gegenüber einer Ernährung mit Omega-6-[for full text, please go to the a.m. URL], 126. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: Infolge einer progredienten Inflammation und Nekrotisierung ist die Prognose der akuten nekrotisierenden Pankreatitis zumeist infaust. In der Literatur wird diskutiert, dass Cyclooxigease-2 einen inhibierenden Einfluß auf die Inflammation bei der akuten nekrotisierenden Pankreatitis[for full text, please go to the a.m. URL], 126. Kongress der Deutschen Gesellschaft für Chirurgie

Background/Aims: The human Anterior Gradient-2 (AGR2) is strongly upregulated in various human cancers, including pancreatic ductal adenocarcinomas (PDAC), but its prognostic value in PDAC has not yet been studied. Methods: We analysed 19 microdissected PDAC cases at the mRNA level, and also 148 cases at the protein level by immunohistochemistry based on tissue microarray, using a monoclonal AGR2 antibody, and statistical analyses were applied to test for prognostic associations. Results: Overexpression of AGR2 mRNA was found to be elevated in most pancreatic cell lines and in microdissected pancreatic cancer compared to microdissected normal ductal cells. AGR2 protein was expressed in 109/148 (73.7%) of PDAC, with a higher expression in female patients (p=0.040), whereas no significant associations with other clinical-pathological parameters were found. A prognostic value of AGR2 could not be demonstrated in univariate analyses. Conclusion: Although a prognostic value of AGR2 seems unlikely, further studies are warranted to investigate the biological role of AGR2 in pancreatic adenocarcinomas.

The WNT signalling pathway plays a central role during embryonic development of multi-cellular organisms, especially for the temporal and spatial specification of organs (e.g. WNT4 in kidney development), a process called pattern formation. Interestingly, genes of the WNT pathway are deregulated in a variety of solid tumours, being considerably up- or down-regulated compared to their expression in the corresponding normal tissue. Some members like WNT1 have demonstrated oncogenic properties in animal models. The SFRP1 gene on chromosome 8 p12 is a negative regulator of the WNT pathway. SFRP1 protein is supposed to bind WNT1 molecules thereby inhibiting the activation of frizzled receptors and the WNT pathway. Characterising an SFRP1-specific antibody we could show that loss of SFRP1 is an extremely common event in breast cancer, i.e. SFRP1 was considerably down-regulated in 73% (n = 1967) of analysed invasive breast cancers. SFRP1 loss is associated with unfavourable prognosis in early breast cancer (pT1 tumours). To analyse the cause of SFRP1 inactivation in breast cancer we performed a parallel expression and promoter methylation analysis in human breast cancer and tumour cell lines. RT-PCR techniques and methylation-specific PCR (MSP) were applied. All tumorigenic cell lines analysed exhibited complete promoter methylation and did not express detectable amounts of SFRP1 mRNA. SFRP1 expression could be restored in these cell lines after treatment with 5-Aza-2'-deoxycytidine, a demethylating agent. Human primary breast cancer was methylated in nearly 75% of cases. Our results indicate that epigenetic inactivation by methylation is the predominant mechanism of SFRP1 gene silencing in breast cancer.