Pathology research international最新文献

Colorectal cancer (CRC) is a heterogeneous disease, developing through a multipathway sequence of events guided by clonal selections. Pathways included in the development of CRC may be broadly categorized into (a) genomic instability, including chromosomal instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP), (b) genomic mutations including suppression of tumour suppressor genes and activation of tumour oncogenes, (c) microRNA, and (d) epigenetic changes. As cancer becomes more advanced, invasion and metastases are facilitated through the epithelial-mesenchymal transition (EMT), with additional genetic alterations. Despite ongoing identification of genetic and epigenetic markers and the understanding of alternative pathways involved in the development and progression of this disease, CRC remains the second highest cause of malignancy-related mortality in Canada. The molecular events that underlie the tumorigenesis of primary and metastatic colorectal carcinoma are detailed in this manuscript.

Colorectal cancer (CRC) is one of the most common causes of death, despite decades of research. Initially considered as a disease due to genetic mutations, it is now viewed as a complex malignancy because of the involvement of epigenetic abnormalities. A functional equivalence between genetic and epigenetic mechanisms has been suggested in CRC initiation and progression. A hallmark of CRC is its pathogenetic heterogeneity attained through at least three distinct pathways: a traditional (adenoma-carcinoma sequence), an alternative, and more recently the so-called serrated pathway. While the alternative pathway is more heterogeneous and less characterized, the traditional and serrated pathways appear to be more homogeneous and clearly distinct. One unsolved question in colon cancer biology concerns the cells of origin and from which crypt compartment the different pathways originate. Based on molecular and pathological evidences, we propose that the traditional and serrated pathways originate from different crypt compartments explaining their genetic/epigenetic and clinicopathological differences. In this paper, we will discuss the current knowledge of CRC pathogenesis and, specifically, summarize the role of genetic/epigenetic changes in the origin and progression of the multiple CRC pathways. Elucidation of the link between the molecular and clinico-pathological aspects of CRC would improve our understanding of its etiology and impact both prevention and treatment.

Historical Background. The ISG criteria for Behcet's, created in 1990, have excellent specificity, but lack sensitivity. The International Criteria for Behcet's Disease (ICBD) was created in 2006, as replacement to ISG. The aim of this study was to compare their performance. ISG and ICBD Criteria. For ISG oral aphthosis is mandatory. The presence of any two of the following (genital aphthosis, skin lesions, eye lesions, and positive pathergy test) will diagnose/classify the patient as BD. For ICBD, vascular lesions were added, while oral aphthosis is no more mandatory. Getting 3 or more points diagnose/classify the patient as BD (genital aphthosis 2 points, eye lesions 2 points, and the remaining each one point). Performance and Comparison of ISG and ICBD. Their sensitivity, specificity, and accuracy (percent agreement), were tested in three independent cohort of patients from Far-East (China), Middle-East (Iran), and Europe (Germany). The sensitivity for ISG was respectively 65.4%, 78.1%, 83.7% and for ICBD 87%, 98.2%, and 96.5%. The specificity for ISG was 99.2%, 98.8%, 89.5% and for ICBD 94.1%, 95.6%, and 73.7%. The accuracy for ISG was 74.2%, 85.5%, 85.5% and for ICBD 88.9%, 97.3%, and 89.5%. Conclusion. ICBD has better sensitivity, and accuracy than ISG.

Aims. Our objective was to examine Apo J protein expression in a total of 27 early liveborn neonatal deaths (less than 7 days of age) selected from the Scottish Perinatal Study (gestation of 25-42 weeks) comparing a group with histological pontosubicular necrosis (PSN) (n = 12) to a control group lacking PSN (n = 15). Methods. Using immunohistochemistry we evaluated postmortem pons and hippocampus from patients with PSN versus controls. Results. In the group with PSN, 11/12 (92%) cases showed positive Apo J neurones in the hippocampus/pons compared with 6/15 (40%) cases without PSN (P = 0.014, odds ratio 27.5, 95% confidence interval 2.881-262.48, using exact logistic regression)-independent of gestation, presence or absence of clinical asphyxia, duration of labour, or postnatal age. Clinical asphyxia was present in 10/15 (67%) without PSN compared with 11/12 (92%) with PSN. Neuronal Apo J positivity was present in 15/21 (71%) of clinically asphyxiated cases compared with 2/6 (33%) of the cases with no evidence of clinical asphyxia (P = 0.154, odds ratio 5, 95% confidence interval 0.71 to 34.94). Conclusions. Apo J neuronal protein expression is significantly increased in cases with PSN compared to cases without PSN-independent of gestation, presence of clinical asphyxia, duration of labour, or postnatal age.

Lynch syndrome (LS) is characterized by an autosomal dominant inheritance of the early onset of colorectal cancer (CRC) and endometrial cancer, as well as increased risk for several other cancers including gastric, urinary tract, ovarian, small bowel, biliary tract, and brain tumors. The syndrome is due to a mutation in one of the four DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. The majority of LS patients and families can now be identified, and the underlying mutation detected using genetic diagnostics. Regular surveillance for CRC and endometrial cancer has proved beneficial for mutation carriers. However, screening for other tumors is also recommended even though experiences in the screening of these tumors is limited. Prophylactic colectomy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy may be reasonable options for selected patients with LS. This paper describes the features and management of LS.

Introduction. The well-documented role of the PDGF system in tumor growth and angiogenesis has prompted the development of new biological agents targeting the PDGF system. The aim of the present study was to analyze the expression of the PDGF-receptors in ovarian cancer and to investigate its relation to histopathological parameters and long-term overall survival. Methods. The immunohistochemical expression of PDGFR-α and PDGFR-β was investigated in tumor and stromal cells in 170 patients with histologically verified epithelial ovarian cancer. Results. Almost half of the tumor specimens showed high expression of PDGFR-α and PDGFR-β in tumor cells (43% and 41%) and in stromal compartments (32% and 44%). There was a significant association between high expression of PDGFR-α and high expression of PDGFR-β in both tumor and stromal cells. Coexpression of PDGFR-α and PDGFR-β in stromal cells was seen more often in serous adenocarcinomas than in nonserous adenocarcinomas. No clear correlation between PDGFR expression and longterm overall survival or clinical parameters was found. Conclusions. PDGFR-α and PDGFR-β were expressed in a subset of ovarian carcinomas but did not show significant prognostic importance in this material.

The incidence of esophageal adenocarcinoma (EAC) has increased exponentially in the last 3 decades. Barrett's esophagus (BE) is the only known precursor of EAC. Patients with BE have a greater than 40 folds higher risk of EAC compared with the general population. Recent years have witnessed a revolution in the clinical and molecular research related to BE. However, several aspects of this condition remain controversial. Data regarding the true prevalence of BE have varied widely. Recent studies have suggested a lower incidence of EAC in nondysplastic BE (NDBE) than previously reported. There is paucity of prospective data showing a survival benefit of screening or surveillance for BE. Furthermore, the ever-increasing emphasis on healthcare cost containment has called for reexamination of the screening and surveillance strategies for BE. There is a need for identification of reliable clinical predictors or molecular biomarkers to risk-stratify patients who might benefit the most from screening or surveillance for BE. Finally, new therapies have emerged for the management of dysplastic BE. In this paper, we highlight the key areas of controversy and uncertainty surrounding BE. The paper discusses, in detail, the current literature about the molecular pathogenesis, biomarkers, histopathological diagnosis, and management strategies for BE.

Endoscopic ultrasound (EUS) is the most sensitive imaging modality for solid pancreatic lesions. The specificity, however, is low (about 75%). It can be increased to 100% with an accuracy of 95% by the addition of fine-needle aspiration (FNA). Cytopathology plays an important role. The final diagnosis is based upon the correlation of clinical, EUS, and cytologic features. A close interaction with the cytopathologist is required in improving the diagnostic yield. In this paper, we present an overview of the role of EUS-guided FNA and importance of close interaction with the cytopathologist. Day to day examples of different solid pancreatic lesions have been presented at the end.

Background. The feasibility and accuracy of immunohistochemistry (IHC) on frozen sections, when assessing sentinel node (SN) status intraoperatively in breast cancer, is a matter of continuing discussion. In this study, we compared a center using IHC on frozen section with a center not using this method with focus on intraoperative diagnostic values. Material and Methods. Results from 336 patients from the centre using IHC intraoperatively were compared with 343 patients from the center not using IHC on frozen section. Final evaluation on paraffin sections with haematoxylin-eosin (HE) staining supplemented with cytokeratin staining was used as gold standard. Results. Significantly more SN with isolated tumor cells (ITCs) and micrometastases (MICs) were found intraoperatively when using IHC on frozen sections. There was no significant difference in the number of macrometastases (MACs) found intraoperatively. IHC increased the sensitivity, the negative predictive value, and the accuracy of the intraoperative evaluation of SN without decreasing the specificity and positive predictive value of SN evaluation. Conclusions. IHC on frozen section leads to the detection of more ITC and MIC intraoperatively. As axillary lymph node dissection (ALND) is performed routinely in some countries when ITC and MIC are found in the SN, IHC on frozen section provides valuable information that can lead to fewer secondary ALNDs.

Behcet's disease is a multisystem disease characterized by recurrent oral and genital ulcers, relapsing uveitis, mucocutaneous, articular, gastrointestinal, neurologic, and vascular manifestations. Rheumatologic manifestations may also occur in Behcet's disease, and arthritis and arthralgia are the most common musculoskeletal findings followed by enthesopathy, avascular necrosis, myalgia, and myositis. Although the main pathology of Behcet's disease has been known to be the underlying vasculitis, the etiology and exact pathogenesis of the disease are still unclear. Musculoskeletal findings of Behcet's disease, the relationship between Behcet's disease and spondyloarthropathy disease complex, and the status of bone metabolism in patients with Behcet's disease were discussed in this paper.