Expression of cadherins and CD44 isoforms in ovarian endometrial cysts

We evaluated the immunohistochemical expression of cadherins and CD44 variants in 20 endometriomas, 20 cystadenomas, 20 borderline ovarian tumours as well as 20 ovarian carcinomas, and the serological and cystic fluid concentrations of soluble E-cadherin and soluble CD44 standard (sCD44sdt) in 20 endometriomas, 20 cystadenomas, six borderline and 11 carcinomas of the ovary. In endometriomas, immunostaining of E- and N-cadherin was negative (20 and 30% respectively). CD44 H, v3 and v6 immunostaining were detected in 63, 10 and 40% respectively. A difference in immunostaining for E-cadherin was found between endometriomas and cystadenomas (P < 0.001) and for N- cadherin between endometriomas and carcinomas (P < 0.001). A difference in CD44H immunostaining was observed between endometriomas and cystadenomas (P < 0.035) but not with borderline ovarian tumours and carcinomas. No difference in serum concentrations of soluble E- cadherins and CD44 standard was found between the four groups of tumours. Cystic fluid concentrations of E-cadherin were lower in endometriomas than in borderline tumours and ovarian carcinomas (P < 0.001). High concentrations of soluble CD44 standard cystic fluid were found in endometriomas than in other ovarian cysts. Endometriomas and borderline tumours share alterations of cadherins and CD44 isoforms which may help in the understanding of the aggressive and invasive potentials of endometriotic cells.      

Detection of a biliary cell membrane glycoprotein in the serum of cholangiocarcinoma-bearing rats. Possible relevance to the membrane proteins used as serum tumor markers in humans

Certain markers used in the diagnosis and monitoring of human adenocarcinomas, such as carcinoembryonic antigen are membrane glycoproteins normally absent from the serum. How those proteins may reach the blood after the neoplastic transformation remains debated. In this work, we show that cholangiocarcinoma induced by 3'-methyl-4-dimethylaminoazobenzene in the rat provides some insight into the mechanisms implicated in this process. We observed that the extracellular matrix of all cholangiocarcinomas tested contained large amounts of a glycoprotein identified by a monoclonal antibody termed B10, and previously characterized as an integral membrane protein normally restricted to the apical domain of epithelial cell plasma membrane. The extracellular deposition of the B10-binding glycoprotein in cholangiocarcinomas was associated with the appearance of detectable levels of the protein in the serum, and an abnormal membrane expression of the protein, which was detected on both apical and basal plasma membrane domains of neoplastic biliary cells. We postulate that neoplastic transformation of biliary cells leads to an inappropriate membrane expression of the B10-binding protein, which in turn, results in the extracellular release of the protein and in its diffusion into the blood. The characteristic desmoplastic stroma of cholangiocarcinoma offers the opportunity to easily visualize the release process. A comparable mechanism is likely to explain how certain membrane glycoproteins used as serum markers in human malignancy may reach the blood.     

Sarcomatoid carcinoma of small intestine: diagnostic problems raised by an unusual tumor

Sarcomatoid carcinomas involving the intestinal tract are rare and usually associated with poor prognosis. We report a case of sarcomatoid carcinoma of the ileum, diagnosed in a 61-year-old man. The patient presented with acute intestinal occlusion. Surgical resection of the ileum was performed. At macroscopic examination, two large polypoid masses were found. Frozen section examination suggested the diagnosis of malignant stromal tumor. At histological examination, both tumors were formed by pleiomorphic, large spindle cells, presenting numerous mitoses and marked nuclear atypia. Immunohistochemical examination showed that tumor cells coexpressed vimentin and epithelial markers (cytokeratins, EMA). The final diagnosis was monomorphic sarcomatoid carcinoma. The patient deceased with metastatic disease after 3 months of follow-up. This report underlines the potential diagnostic problems raised by this unusual type of carcinoma and emphasizes the role of immunohistochemistry in assessing the correct diagnosis.     

Angiogenesis in the neoplastic sequence of Barrett's oesophagus. Correlation with VEGF expression

The purpose of this study was to determine the angiogenic profile of human oesophageal adenocarcinoma. This study was carried out on a large series of surgically resected Barrett's adenocarcinomas and associated preneoplastic lesions. Vascularization was quantified by microvessel counting and measurement of the percentage microvessel surface area after immunohistochemistry using the CD34 antibody. The expression of vascular endothelial cell growth factor (VEGF) was also examined by immunohistochemistry. Results were correlated with clinico-pathological data and prognosis. Vascularization, assessed by both microvessel counting and measurement of the microvessel surface, was statistically higher in superficial cancers than in others. Higher vascularization was correlated with a lower rate of lymph node and distant metastasis, as well as with better survival. However, when superficial carcinomas were excluded from the study, microvessel count failed to provide any significant prognostic information. Irrespective of the inclusion or exclusion of superficial tumours, the expression of VEGF was correlated with a higher vascularisation but did not provide prognostic significance. It is concluded that high angiogenic properties are acquired in precancerous lesions and early cancers in Barrett's oesophagus. Vascularization as assessed by both microvessel counting and measurement of the microvessel surface is not informative for prognosis in infiltrative Barrett's adenocarcinomas. The expression of VEGF is correlated with vascularization, but has no independent prognostic relevance.     

Mixed endocrine tumors

Mixed endocrine tumors are tumors composed of at least two distinct tumor populations, one of which is endocrine. Because of their rarity and unusual presentation, endocrine mixed tumors raise many problems of diagnosis, management and therapy. Three main types of endocrine mixed tumors are recognized: The existence of these various types has been confirmed by recent molecular studies, even if the same studies have also shown that the histogenesis of a mixed endocrine tumor cannot be predicted from its histological features. Composite tumors are the less rare mixed tumors. The recent WHO classification recommends to restrict the term of composite endocrine tumor to the epithelial tumors containing at least 30% of obviously tumoral endocrine cells; some authors recommend to use higher thresholds, of at least 50%, in order to avoid overdiagnosis. The endocrine component is usually well differentiated, easily identified by its suggestive histological features; the endocrine nature of tumor cells is confirmed by the immunodetection of specific endocrine and neuro-endocrine markers (such as chromogranin A and synaptophysin). In some cases, the endocrine component is poorly differentiated: the demonstration of neuro-endocrine markers is necessary to confirm the diagnosis. Mixed tumors can occur in every anatomical site; they are more frequent in organs containing endocrine cells in the normal state (especially the digestive tract and the pancreas), but they can also be observed in organs devoid of endocrine cells (such as the mammary gland). The management of mixed endocrine tumors must take into account the more aggressive component. Mixed tumors containing a well differentiated endocrine component and an adenocarcinomatous component are to be treated like adenocarcinomas. Mixed tumors containing a poorly differentiated endocrine component must be considered as poorly differentiated endocrine carcinomas.     

Problématique des marqueurs histopronostiques dans les tumeurs neuroendocrines digestives

The evaluation of prognosis is essential for the management of a patient with a neuroendocrine tumor, especially digestive, in which the risk of malignancy is significant. Three validated histoprognostic factors are available from the pathological examination: morphological differentiation status, histological grade, and pTNM stage. Numerous prognostic biomarkers have been proposed in the literature but none has been transposed to clinical practice. In the sameway, among the candidate predictive biomarkers, only MGMT is an emerging biomarker, which may be useful for the prediction of the response to temozolomide.