Bray S E, Paulin F E M, Fong S C, Baker L, Carey F A, Levison D A, Steele R J C & Kernohan N M (2010) Histopathology56, 240–250 Gene expression in colorectal neoplasia: modifications induced by tissue ischaemic time and tissue handling protocol Aims: The heterogeneity within individual distinct cancer types in terms of behaviour, response to therapy and prognosis is well recognized. A major goal of translational research projects has therefore been to define clinically significant subgroups of individual tumour types by analysis of mRNA as well as protein expression. An essential premise of such investigations is that expression of these key molecules is a true reflection of conditions present within the neoplastic cells in vivo. The aim was to investigate the effect of methods of tissue handling and storage on expression of mRNA.Methods and results: mRNA expression in 60 biopsy samples obtained from 10 patients with colorectal tumours was examined. The mRNA expression profile and the level of expression of specific mRNA species were significantly affected by the procedures used for collection and storage of tissue samples. Significant variation in the level of expression (both increased and decreased) of transcripts was detectable after 15 min, and by 120 min there was a fourfold increase in the number of genes with a more than twofold change in the level of expression.Conclusions: Reliable interpretation of results of gene expression at the mRNA level requires standardized protocols for tissue procurement.

We sought to determine whether seliciclib (CYC202, R‐roscovitine) could increase the antitumor effects of doxorubicin, with no increase in toxicity, in an MCF7 breast cancer xenograft model. The efficacy of seliciclib combined with doxorubicin was compared with single agent doxorubicin or seliciclib administered to MCF7 cells and to nude mice bearing established MCF7 xenografts. Post‐treatment cells and tumors were examined by cell cycle analysis, immunohistochemistry and real‐time PCR. Seliciclib significantly enhanced the antitumor effect of doxorubicin without additional murine toxicity. MIB1 (ki67) immunohistochemistry demonstrated reduced proliferation with treatment. The levels of p21 and p27 increased after treatment with doxorubicin or seliciclib alone or in combination, compared to untreated controls. However, no changes in p53 protein (DO1, CM1), survivin or p53 phosphorylation (SER 15 ) were observed in treated tumors compared with controls. In conclusion, the CDK inhibitor seliciclib (R‐roscovitine) enhances the antitumor effect of doxorubicin in MCF7 tumors without increased toxicity with a mechanism that involves cell cycle arrest rather than apoptosis. © 2008 Wiley‐Liss, Inc.

Follicular lymphoma (FL) is a common subtype of low grade B-cell non-Hodgkin lymphoma (NHL). Although this form of lymphoma often pursues an indolent course, in some cases it may behave in a more aggressive manner. Clinical and histological parameters have been shown to correlate with an adverse prognosis but a number of cytogenetic abnormalities may also be associated with aggressive disease. Although, the t(14;18) in itself does not affect outcome in cases of FL, secondary abnormalities that occur in a complex polyploid karyotype may identify cases with a poor prognosis. It is unusual to find both t(14;18) and C-MYC translocation in the same tumour; those cases in which it has been described include examples of high-grade B-cell NHL (either de novo or transformed FL) or B-cell acute lymphoblastic lymphoma. In this report, three cases of FL are described in which both t(14;18) and a C-MYC translocation were identified at presentation. We also summarize four further cases from the literature. This is a small series but one which raises the possibility that the presence of a C-MYC translocations at presentation may identify a particularly aggressive subtype of FL. Further studies are required to investigate the true incidence of this aberration, the impact on C-MYC regulation, clinical course and response to treatment.

Kikuchi's disease is a rare self- limiting lymphoproliferative condition of unknown aetiology, characterised by acute or subacute necrotising lymphadenitis. It is a benign condition that can mimic malignant lymphoma. In this report, a case of Kikuchi's disease associated with a chromosomal abnormality is described. This is the first report in the literature of such a case and it highlights an important learning point; benign lymphoproliferative conditions can be associated with chromosomal abnormalities that are more typically associated with malignant lymphoproliferative conditions such as malignant lymphoma. The report illustrates the necessity for interpreting cytogenetic data in the relevant clinical and histopathological context in a multidisciplinary setting to avoid misdiagnosis and inappropriate treatment.

There is a leading article in this issue of Medical Teacher entitled ‘Learning Syndromes Afflicting Beginning Medical Students: Identification and Treatment––Reflections after Forty Years of Teaching’. This is one of these rare articles which clearly articulates things that a reader may have only partly understood previously, or only subconsciously known. It is an article which looks at how medical students study, and is written by an obviously perceptive individual who has been teaching medical students and thinking about what he has been doing for over 40 years. In the article he identifies various study strategies used by medical students, and he gives each approach to learning a name which reflects the underlying problem of that particular approach–– and then the good bit––he analyses what is wrong with that approach and suggests ways of dealing with the problem. Though some of the flawed study patterns or syndromes are more readily recognizable than others, I am sure that all of them will ring a bell with most medical teachers and many students. For example, there is the Oh yeah?? Syndrome in which the student thinks he or she knows and fully understands the topic under discussion because they have come across it before either at school or in an earlier course. Such an attitude often leads to a failure to appreciate the new depth of understanding and knowledge required, minimal study time devoted to the topic, and a consequent poor performance at assessment. The suggested solution is not rocket science but sound common sense––namely warning the students about this possible situation and reminding them that they need to learn the material to the depth of understanding required by the medical course. In fact the advice offered by the author for dealing with all of these syndromes is very straightforward in most cases, and I am sure will be of value to any medical student who reads it. Though the article is written in a North American context, the problems identified and the solutions are universally relevant. I think this article should be made compulsory reading for course organizers in all medical schools and all new medical students.

In surgical practice, patients present with intestinal symptoms which may be due to a benign or malignant tumour within the bowel. The symptoms, histological type of tumour, and frequency of occurrence vary according to the region of the bowel affected; some tumour types are more common in specific locations in the bowel. By far the most common tumours (benign and malignant) seen in surgical practice are those of epithelial origin occurring in the large bowel. Small bowel tumours and non-epithelial (e.g. mesenchymal, lymphoid) tumours occur, but with a lower frequency. Benign tumours do not invade or metastasize. They produce their symptoms due to a mass effect which can cause luminal narrowing, compression of surrounding structures, mechanical obstruction and/or a focus for torsion or intussusception. They can also release factors into the systemic circulation such as gastrin, causing Zollinger–Ellison Syndrome, characterized by intractable gastric acid secretion, severe peptic ulceration of the duodenum and jejunum and hypergastrinaemia, or serotonin, causing carcinoid syndrome, respectively. Malignant tumours can invade locally, but can also spread to sites outside the bowel. Signs and symptoms can be due to the mass effect similar to that seen with benign tumours, but also can be due to invasion of surrounding structures and other organs (e.g. liver). This review aims to give a general overview of the pathology of tumours occurring throughout the bowel, mainly focusing on those commonly seen in surgical practice.

Individual pathologists deal with thousands of diagnostic biopsy and excision specimens annually. At each stage, procedures are in place to limit the possibility of human error, which could result in specimen transposition or contamination. One specimen contaminating another is usually easily identified and rarely causes diagnostic difficulty; however, when it does, the consequences can be very serious. We discuss 5 cases in which concerns over specimen identity and tissue contamination arose and the methodology by which we resolved those concerns. Polymerase chain reaction analysis of each case was carried out using a panel of 12 polymorphic microsatellite markers, specific for chromosomes 13, 18, and 21. These markers are routinely used in the molecular genetics diagnostic laboratory for rapid trisomy screening. In each case, the question of error was satisfactorily resolved. Using this approach, we prevented the real possibility of patients undergoing second invasive procedures. We suggest that this or a similar methodology become a routine part of pathology practice.

Endocrine Soft Tissue Skin Renal Respiratory System Nervous System Male Genital Tract Lymphoreticular System Liver and Biliary Tract Upper Aerodigestive Tract Gastrointestinal Tract Female Genital Tract Bone Bone Marrow Breast Gynaecological Cytology Fine Needle Aspiration Cytology

Immunohistochemical methods using antibodies to cell cycle-related antigens may be used as a means of assessing various aspects of proliferation in tissue, and have the important advantage of preserving the spatial orientation of proliferating cells in histological sections. Currently, the most widely available antibodies for this purpose are antibodies to bromodeoxyuridine (BrdU), Ki67 and antibodies to proliferating cell nuclear antigen (PCNA). BrdU is a thymidine analogue incorporated during the S phase of the cell cycle, which can be introduced by ‘in vivo’ administration or by ‘in vitro’ incubation, and monoclonal antibodies are available to display its localization. Ki67 demonstrates a nuclear antigen expressed in all phases of the cell cycle, except G0 and early G1, but can only be applied to frozen tissue. PCNA is a nuclear antigen which is essential for DNA synthesis, two commercially available antibodies to PCNA work in paraffin-embedded tissue, but may have different staining characteristics under different conditions of fixation. The main advantages and disadvantages of these different techniques are discussed, together with their main applications to date.