Gastroenterology 01/1998; 114. · 12.82 Impact Factor
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ABSTRACT: The incidence of oesophageal adenocarcinoma has significantly increased in Europe over the last 30 years. The progression from normal mucosa to adenocarcinoma has been associated with genetic and morphological traits regrouped under the term "intraepithelial neoplasia" (IEN) according to the Vienna classification. The early detection of such lesions represents the first step in the identification of high-risk patients. The morphological criteria of IEN are the gold standard to identify such patients. Firstly described by Riddell et al in 1983, IEN is based on morphological criteria including both cytological and architectural alterations and is classified into different stages of severity. However, large studies have clearly demonstrated the lack of reproducibility, with large inter-individual discrepancies for both discrete and severe lesions. Discrepancies between high grade IEN and adenocarcinoma can be minimized by using the Vienna classification, which groups both of these lesions under the "stage IV". Discrepancies between low-grade IEN and uncertain lesions remain too important. Erroneous and overstated diagnosis of low grade IEN induces an unnecessary follow-up of patients with obvious psychological and economic consequences. Recent studies have demonstrated that the reading of the slides by 2 to 3 gastrointestinal (GI) pathologists significantly decreases interpretation mistakes. Because of these interpretation problems, scientists have looked for non-morphological criteria to confirm the pre-cancerous state. The current PubMed literature proposes many putative biomarkers. However, none of these has been correctly validated in large prospective case-control studies, which hampers their use in clinical routine. DNA quantification by flux cytometry and morphometry represent alternative methods of documenting IEN but these techniques are complex and expensive. The use of the proliferation marker Ki67 needs deep sampling with correct orientation and standardized cell counting. P504 S has been studied in Barrett's disease and might be a novel tool. The only promising tool thus far is the overexpression of p53 as shown in prospective studies demonstrating a nice correlation with clinical evolution and is easy to use in clinical routine.
Acta gastro-enterologica Belgica 72(4):425-32. · 0.58 Impact Factor
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ABSTRACT: Patients with metastatic colorectal cancer and KRAS mutation are unlikely to benefit from treatment with anti-EGFR antibodies, and testing for KRAS mutation in this setting is recommended. Pathologists have a crucial role in accurate testing for KRAS mutations, whether or not testing is performed in their own laboratory, as mutation analysis is performed on paraffin embedded tissue selected by the pathologists. The type of fixative used is a very important issue, as some fixatives do not allow molecular testing. Pathologists must select the most appropriate tumoral tissue block for KRAS mutation analysis and hence, must know the sensitivity of the KRAS mutation detection methodology utilized in their reference laboratory. It is essential that they select a tissue block that contains enough percentage of viable tumour cells, as false negative results will occur when the sample is contaminated with high levels of nontumour elements. Pathologists not only have to recognize the area of invasive carcinoma and distinguish it from non-invasive neoplastic components, but also have to estimate the percentage of necrotic debris and nontumoural elements. For tests that require a high percentage of tumour cells, macrodissection before extraction of nucleic acids is often indicated. The primary pathologists in addition are responsible for preparation of the pathology report for the tissue block on which the KRAS mutation analysis was performed and should transmit the results to the requesting clinician. Pathologists should participate in a multidisciplinary oncologic consult to achieve correct interpretation of the results e.g. in case of potential false negative results.
Acta gastro-enterologica Belgica 73(4):497-503. · 0.58 Impact Factor