Loss of Ep-CAM (CO17-1A) expression predicts survival in patients with gastric cancer

Preoperative staging of gastric cancer is difficult and not optimal. The TNM stage is an important prognostic factor, but it can only be assessed reliably after surgery. Therefore, there is need for additional, reliable prognostic factors that can be determined preoperatively in order to select patients who might benefit from (neo) adjuvant treatment. Expression of immunohistochemical markers was demonstrated to be associated with tumour progression and metastasis. The expression of p53, CD44 (splice variants v5, v6 and v9), E-cadherin, Ep-CAM (CO17-1A antigen) and c-erB2/neu were investigated in tumour tissues of 300 patients from the Dutch Gastric Cancer Trial, investigating the value of extended lymphadenectomy compared to that of limited lymphadenectomy). The expression of tumour markers was analysed with respect to patient survival. Patients without loss of Ep-CAM-expression of tumour cells (19%) had a significantly better 10-year survival (P<0.0001) compared to patients with any loss: 42% (s.e.=7%) vs 22% (s.e.=3%). Patients with CD44v6 (VFF18) expression in more than 25% of the tumour cells (69% of the patients) also had a significantly better survival (P=0.01) compared to patients with expression in less than 25% of the tumour cells: 10 year survival rate of 29% (s.e.=3%) vs 19% (s.e.=4%). The prognostic value of both markers was stronger in stages I and II, and independent of the TNM stage. Ep-CAM and CD44v6-expression provides prognostic information additional to the TNM stage. Loss of Ep-CAM-expression identifies aggressive tumours especially in patients with stage I and II disease. This information may be helpful in selecting patients suitable for surgery or for additional treatment pre- or postoperatively

Immunohistochemical biomarkers are prognostic relevant in addition to the ESMO-ESGO-ESTRO risk classification in endometrial cancer

ObjectivePre-operative immunohistochemical (IHC) biomarkers are not incorporated in endometrial cancer (EC) risk classification. We aim to investigate the added prognostic relevance of IHC biomarkers to the ESMO-ESGO-ESTRO risk classification and lymph node (LN) status in EC.MethodsRetrospective multicenter study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), analyzing pre-operative IHC expression of p53, L1 cell-adhesion molecule (L1CAM), estrogen receptor (ER) and progesterone receptor (PR), and relate to ESMO-ESGO-ESTRO risk groups, LN status and outcome.ResultsA total of 763 EC patients were included with a median follow-up of 5.5-years. Abnormal IHC expression was present for p53 in 112 (14.7%), L1CAM in 79 (10.4%), ER- in 76 (10.0%), and PR- in 138 (18.1%) patients. Abnormal expression of p53/L1CAM/ER/PR was significantly related with higher risk classification groups, and combined associated with the worst outcome within the ‘high and advanced/metastatic’ risk group. In multivariate analysis p53-abn, ER/PR- and ESMO-ESGO-ESTRO ‘high and advanced/metastatic’ were independently associated with reduced disease-specific survival (DSS). Patients with abnormal IHC expression and lymph node metastasis (LNM) had the worst outcome. Patients with LNM and normal IHC expression had comparable outcome with patients without LNM and abnormal IHC expression.ConclusionThe use of pre-operative IHC biomarkers has important prognostic relevance in addition to the ESMO-ESGO-ESTRO risk classification and in addition to LN status. For daily clinical practice, p53/L1CAM/ER/PR expression could serve as indicator for surgical staging and refine selective adjuvant treatment by incorporation into the ESMO-ESGO-ESTRO risk classification.</p

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research

Expression of a colorectal antigen defined by a new monoclonal antibody, CO-TL1.

Contains fulltext : 58500.pdf (publisher's version ) (Closed access)A murine monoclonal antibody (MoAb CO-TL1, IgG1) has been raised by differential screening of hybridoma supernatants on sections of human large and small intestines, followed by screening on colon adenomas as well as on colorectal carcinomas. In both paraffin sections and cryostat sections, the antibody stained strongly all cell types in adult, neonatal and fetal human colorectal epithelium, that is, the goblet cells, the columnar cells and the endocrine cells. No staining was observed in the remaining parts of the normal gastrointestinal tract and other tissues. As revealed by immuno electron microscopy the epitope was present in the apical and basolateral cell membranes, the Golgi complex, secretory vesicles of goblet and columnar cells, and also in granules of the endocrine cells. The epitope in colorectal tissue sections was resistant to the deglycosylation enzymes neuramidase, diastase and hyaluronidase indicating its proteinaceous nature. This colorectal antigen remained expressed in 100% of colorectal adenomas (n = 39) and 86% (n = 29) of colorectal carcinomas. The expression was reduced in undifferentiated carcinomas. The CO-TL1 antibody detected also most other gastrointestinal adenocarcinomas and a few carcinomas of the ovary, uterus, breast, gallbladder and pancreas. However, it never detected carcinomas derived from the thyroid, lung, liver, bladder, kidney, prostate, testis, serous membranes of body cavities and skin. A wild-type variant protein of > 300 kDa of the colorectal antigen was identified in normal colorectal epithelium. In colorectal tumours, however, two tumour variant forms were found of 160-200 and 115-140 kDa, respectively. Our data indicate that this new MoAb CO-TL1 can be considered as a useful marker, which identifies normal colorectal epithelium and gastrointestinal tumours and especially colorectal tumours with high accuracy and excludes tumours originated from thyroid, lung, liver, bladder, kidney, prostate, testis, mesothelium and skin