A Driessen

Identical cytokeratin expression pattern CK7+/CK20− in esophageal and cardiac cancer: etiopathological and clinical implications

Surgical treatment and prognosis is different in esophageal, cardiac and distal gastric adenocarcinomas. Determination of the origin, in particular of adenocarcinomas situated at the gastroesophageal junction, may be difficult. It has been suggested that esophageal adenocarcinomas are characterized by a specific cytokeratin pattern, namely the CK7+/CK20− pattern. According to the same authors, this cytokeratin pattern is absent in gastric adenocarcinomas. The aim of our study is to evaluate if this cytokeratin pattern CK7+/CK20− is absent in cardiac and distal gastric adenocarcinomas. Therefore, we evaluated the combined immunohistochemical expression of CK7 and CK20 on paraffin-embedded material of 214 resection specimens for adenocarcinoma, comprising 66 esophageal, 73 cardiac and 75 distal gastric adenocarcinomas (UICC-classification). The adenocarcinomas were subtyped into intestinal- and diffuse-type according to the Lauren classification. The immunohistochemical staining was considered as positive if 50% or more of the tumor cells were stained. Statistical analysis has been performed applying the χ2-test. The tumors situated at the gastroesophageal junction, esophageal as well as cardiac adenocarcinomas, showed predominantly a CK7+/CK20− expression pattern (67 vs 68%), whereas this cytokeratin pattern is rather uncommon in distal gastric adenocarcinomas (31%, P<4 × 10−5). Independent of their localization, intestinal- as well as diffuse-type adenocarcinomas have a similar cytokeratin pattern. Our data show that the combined expression of CK7 and CK20 is different for the adenocarcinomas situated on both sides of the gastroesophageal junction compared to the distal gastric adenocarcinomas. However, in contrast to data in the literature, the combined expression of CK7 and CK20 has a low specificity in the distinction between esophageal and cardiac adenocarcinomas. This may suggest a similar origin (cell lineage) and thus may have an impact on therapeutic strategies.

Are carcinomas of the cardia oesophageal or gastric adenocarcinomas

There is a clear relationship between Barretts oesophagus and oesophageal adenocarcinoma, and between Helicobacter pylori and gastric cancer, but the histogenesis of cardiac adenocarcinomas is unknown. Some clues as to possible disease associations may be provided by the pattern of gastritis. In our study, we analysed gastritis associated with oesophageal, cardiac and gastric adenocarcinomas according to the Sydney classification. Chronic gastritis was more common in gastric (88%) than in cardiac (56%) and oesophageal adenocarcinomas (38%). H. pylori was significantly more prevalent in gastric (73%) than in cardiac (34%) or oesophageal (21%) adenocarcinomas. Our results show that factors other than H. pylori must be involved in the histogenesis of cardiac adenocarcinomas. As the pattern of gastritis and the clinical features of cardiac adenocarcinomas are more comparable to oesophageal carcinomas than gastric carcinomas, we speculate that most of these tumours share similar aetiological factors with oesophageal carcinomas.

Primary diffuse large B cell lymphoma of the stomach : analysis of somatic mutations in the rearranged immunoglobulin heavy chain variable genes indicates antigen selection

Gastric low grade MALT lymphomas show a pattern of somatic mutations in their rearranged immunoglobulin genes, indicative of antigen selection. This provides evidence for antigen stimulation in the lymphomagenesis. Gastric diffuse large B cell lymphomas develop secondary to low grade MALT lymphoma or de novo. To study whether antigen-selection is also a feature of primary diffuse large B cell lymphomas, we analysed somatic mutations in the rearranged immunoglobulin heavy chain (IgH) variable genes (VH). The rearranged VH genes of six cases of gastric primary diffuse large B cell lymphoma were amplified from genomic or complementary DNA by a VH gene family-specific polymerase chain reaction method. The PCR products were directly sequenced and were compared to published germline sequences to analyse somatic mutations. Similarly to low grade MALT lymphomas 5/6 primary diffuse large B cell lymphomas show a pattern of somatic mutation in their rearranged VH genes, indicative of antigen selection and suggesting a role for antigens in lymphomagenesis. One case showed bi-allelic VH gene rearrangements, which were non-functional due to extensive deletions. Antigen selection could not be demonstrated or excluded. Antigen selection is a common feature in most analysed primary diffuse large B cell lymphomas, although some heterogeneity in the mechanisms involved in the lymphomagenesis of gastric primary diffuse large B cell lymphomas has not been excluded entirely (case 4).

Histological and immunohistochemical study of the lymphoid tissue in the normal stomach of the gnotobiotic pig

Abstract. Animal models have been developed in which the role of Helicobacter pylori in the pathogenesis of different gastroduodenal diseases can be investigated. The gnotobiotic pig was one of the first animal models used. In this model, Helicobacter pylori infection causes gastritis, which shows some similarities to that in humans, such as the development of mucosa-associated lymphoid tissue (MALT). Hence, this animal model can be used to study the development of MALT in the normal stomach. The aim of our study is to see if lymphoid tissue is present or absent in the normal stomach of gnotobiotic pigs before birth and if so, to investigate its development and composition as a function of gestational age and location in the stomach. Therefore, we studied 82 foetal piglets using routine histology and immunohistochemistry. Our findings show that lymphoid tissue is present at birth. It is composed of lymphoid nodules, a diffuse mononuclear infiltrate and intra-epithelial lymphocytes. The development is a sequential process. The lymphoid tissue in the stomach at birth is composed of the immunohistochemically different immunocompetent cells normally present. In conclusion, MALT is present in normal foetal gnotobiotic pig gastric mucosa, and in this model the stomach is no exception to the rest of the gastrointestinal tract.

La réaction de la polymérase en chaîne constitue un important apport dans le diagnostic et le suivi des lymphomes gastriques

RésuméEn dépit de critères morphologiques bien établis, le diagnostic d’un infiltrat lymphoïde néoplasique requiert un complément d’examens immunocytochimiques et de biologie moléculaire afin de prouver son origine clonale. Etant donné les limites de l’immunocytochimie, les techniques de biologie moléculaire telles que le Southern blot et la PCR s’imposent. Ses nombreux désavantages contre-indiquent le Southern blot comme méthode de routine dans le diagnostic des lymphomes gastriques. Par contre, la PCR est une technique moléculaire d’utilisation courante en raison de sa simplicité, sa rapidité, son coût modéré et sa haute sensibilité. Cependant, cette méthode peut montrer des réarrangements géniques clonaux dans des conditions réactionnelles telles que les gastrites. Ses résultats doivent dès lors être interprétés en fonction de la présentation clinique. Comme des réarrangements géniques clonaux peuvent précéder le développement d’une tumeur, un suivi minutieux du patient est à conseiller.SummaryDespite the well-established morphological criteria of gastric lymphomas, the diagnosis of a neoplastic lymphoid infiltrate requires an immunohistochemical or molecular pathological examination to prove its clonal origin. Because of the limitations of immunohistochemistry, molecular techniques, such as Southern blot and PCR, are necessary. The numerous disadvantages of Southern blot hamper however its use as routine diagnostic method in gastric lymphomas. In contrast PCR is a popular molecular technique because of its simplicity, rapidity, costeffectiveness and high sensitivity. Since this method may demonstrate clonal gene rearrangements in reactive conditions, such as gastritis, results have always to be interpreted in function of the clinical presentation of the patient. As clonal gene rearrangements may precede the development of the tumour, a thorough follow-up of this patient is advisable.

La technique de PCR est une méthode plus précise pour déterminer la monoclonalité des lymphomes gastriques

RésuméBien que les critères morphologiques en soient bien établis, le diagnostic du lymphome gastrique à partir de biopsies gastriques endoscopiques reste très difficile. Pour confirmer la nature néoplasique de l’infiltrat, il faut prouver qu’il est monoclonal. Puisque les succès obtenus en immuno-histochimie demeurent limités, de nouvelles techniques ont été développées au niveau moléculaire. Sa simplicité, son coût réduit, sa rapidité et sa grande sensibilité expliquent le succès de la technique de PCR. Sa grande sensibilité est cependant un inconvénient car un infiltrat monoclonal peut être retrouvé non seulement dans un lymphome gastrique mais aussi lors d’une gastrite. Ainsi, les résultats de cette technique doivent toujours être corrélés avec la morphologie des biopsies gastriques et le tableau clinique du patient.SummaryAlthough the morphological criteria are well-established, the diagnosis of gastric lymphoma on gastric endoscopic biopsies remains very difficult. To confirm the neoplastic origin of the infiltrate, the monoclonal nature of the infiltrate has to be proven. Since the success of immunohistochemistry is limited, new techniques on molecular level have been developed. Simplicity, cost-effectiveness, rapidity and high sensitivity explain the success of the polymerase chain reaction. Its high sensitivity is however a drawback of the technique as a monoclonal infiltrate is not only found in gastric lymphomas but also in gastritis. Hence the results of this technique have always to be correlated with the morphology of the gastric biopsies and the clinical presentation of the patient.