Although young patients present with more aggressive histopathological subtypes and less early stages, cancer-related survival is not less favourable compared with older patients.

BackgroundAccurate histopathological evaluation of resected lymph nodes (LN) is essential for the reliable staging of colorectal carcinomas (CRC). With conventional sectioning and staining techniques usually only parts of the LN are examined which might lead to incorrect tumor staging. A molecular method called OSNA (One Step Nucleic Acid Amplification) may be suitable to determine the metastatic status of the complete LN and therefore improve staging.MethodsOSNA is based on a short homogenisation step and subsequent automated amplification of cytokeratin 19 (CK19) mRNA directly from the sample lysate, with result available in 30-40 minutes. In this study 184 frozen LN from 184 patients with CRC were investigated by both OSNA and histology (Haematoxylin & Eosin staining and CK19 immunohistochemistry), with half of the LN used for each method. Samples with discordant results were further analysed by RT-PCR for CK19 and carcinoembryonic antigen (CEA).ResultsThe concordance rate between histology and OSNA was 95.7%. Three LN were histology+/OSNA- and 5 LN histology-/OSNA+. RT-PCR supported the OSNA result in 3 discordant cases, suggesting that metastases were exclusively located in either the tissue analysed by OSNA or the tissue used for histology. If these samples were excluded the concordance was 97.2%, the sensitivity 94.9%, and the specificity 97.9%. Three patients (3%) staged as UICC I or II by routine histopathology were upstaged as LN positive by OSNA. One of these patients developed distant metastases (DMS) during follow up.ConclusionOSNA is a new and reliable method for molecular staging of lymphatic metastases in CRC and enables the examination of whole LN. It can be applied as a rapid diagnostic tool to estimate tumour involvement in LN during the staging of CRC.

Most myenteric neurons contain one of the two generating enzymes for major excitatory and inhibitory neurotransmitters: choline acetyltransferase (ChAT) or neuronal nitric oxide synthase (NOS). Two minor groups of myenteric neurons contain either both enzymes or neither. Our study had two aims: (1) to compare the proportions of neurons stained for ChAT and/or NOS in human small and large intestinal whole-mounts by co-staining with an antibody against the human neuronal protein Hu C/D (HU); (2) to characterize these neurons morphologically by co-staining with a neurofilament (NF) antibody. In small intestinal whole-mounts co-stained with HU, we counted more ChAT-positive (ChAT+) than NOS+ neurons (52% vs. 38%), whereas the large intestine exhibited fewer ChAT+ than NOS+ neurons (38% vs. 50%). Neurons co-reactive for both ChAT and NOS accounted for about 3% in both regions, whereas neurons negative for both enzymes accounted for 7% in the small intestine and 8% in the large intestine. Co-staining with NF revealed that, in both small and large intestine, ChAT+/NOS+ neurons were either spiny (type I) neurons or displayed smaller perikarya that were weakly or not NF-stained. Of all spiny neurons, almost one third was co-reactive for ChAT and NOS, whereas nearly two thirds were positive only for NOS. Neurons negative for both ChAT and NOS were heterogeneous in size and NF reactivity. Thus, neither the co-existence nor the co-absence of ChAT and NOS in human myenteric neurons is indicative for particular neuron types, with several qualitative and quantitative parameters showing a wide range of interindividual variability.

Chronic hepatitis C patients with the MTP -493T allele reveal higher grades of steatosis, indicating a relevant contribution to liver fat accumulation, particularly in HCV non-3 patients.

The oncofetal protein, insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3), has been analyzed in many different tumors. Various studies have found that IMP3 is a marker for malignancy and is correlated with increased tumor aggressiveness and reduced overall survival. The diagnosis of pancreatic ductal adenocarcinoma (PDAC) in core needle biopsies can be challenging, and immunohistochemical markers are needed. We studied IMP3 expression in 177 core needle biopsies of the pancreas, including 112 PDACs, 55 cases with chronic sclerosing pancreatitis, and 10 biopsies with tumor-free pancreatic tissue without inflammation. An additional 18 biopsies of PDAC metastases (16 liver biopsies and 2 lymph node biopsies) were analyzed. To study IMP3 expression in large tissue sections, 45 pancreatic resection specimens (26 with PDAC and 19 with chronic sclerosing pancreatitis) were investigated. In contrast to normal or inflamed pancreatic tissue, which was negative in 47 of 65 (72.3%) cases and weakly positive in 15 of 65 (23.1%) cases, strong IMP3 expression was found in 99 of 112 (88.4%) PDACs. Therefore, sensitivity and specificity of IMP3 expression in the differential diagnosis of PDAC and chronic sclerosing pancreatitis using core needle biopsies were found to be 88.4% and 94.6%, respectively. These results were confirmed in the pancreas resection specimens. Furthermore, strong IMP3 expression was found in 17 of 18 (94.4%) of the PDAC metastases that were analyzed. Our study shows that IMP3 is an easy to use and potentially new immunohistochemical marker for the diagnosis of PDAC in core needle biopsies.