Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study.

BACKGROUND: Epithelioid peritoneal malignant mesothelioma (EPMM) is the most common subtype of this aggressive tumor. We compared two antibodies against PD-L1, a recent theranostic biomarker, and evaluated the prognostic value of PD-L1 expression by mesothelial and immune cells in EPMM. METHODS: Immunohistochemistry was performed on 45 EPMM. Clinical and pathological data were extracted from the RENAPE database. Using E1L3N and SP142 clones, inter-observer agreement, PD-L1 expression by mesothelial and immune cells and inter-antibody agreement were evaluated. The prognostic relevance of PD-L1 expression was evaluated in 39 EPMM by univariate and multivariate analysis of overall survival (OS) and progression-free survival (PFS). RESULTS: Inter-observer agreement on E1L3N immunostaining was moderate for mesothelial and immune cells, and fair for mesothelial and poor for immune cells using SP142. Using E1L3N, 31.1% of mesothelial and 15.6% of immune cells expressed PD-L1, and 22.2% of mesothelial and 26.7% of immune cells using SP142. Inter-antibody agreement was moderate. In most positive cases, 1-5% of tumor cells were positive. Using E1L3N, PD-L1 expression by lymphocytes was associated with better OS and PFS by both univariate and multivariate analysis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy predicted better prognosis than other treatments. Solid subtype was an independent prognostic factor for worse OS. CONCLUSION: E1L3N appeared easier to use than SP142 to evaluate PD-L1 expression. A minority of EPMM expressed PD-L1, and only a few cells were positive. PD-L1 expression by immune cells evaluated with E1L3N was an independent prognostic factor in EPMM.

Metabolomic Characterization of Ovarian Epithelial Carcinomas by HRMAS-NMR Spectroscopy.

Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i) discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii) generate statistical models capable of classifying borderline tumors and (iii) establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using (1)H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate) and mucinous (N-acetyl-lysine) carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients.

[Activity and cost analysis in surgical pathology. Experience of a French university laboratory using the activity-based costing method]. / Mesure de l'activité et des coûts en ACP hospitalo-universitaire par la méthode ABC (activity-based costing).

Good self-knowledge enables us to have a well- reasoned adaptation to our environment. Starting from this precept based on simple common sense, activity and cost analysis, when applied to medical departments in a university hospital setting, represents a necessary phase in their scientific progression and in the continuation of their university vocation. This is all the more true given the present climate of economic and organizational restructuring of medical facilities. This paper relates the experience of a French surgical pathology department which was assessed for cost effectiveness using the Activity-Based Costing (ABC) method in 1999. This method, which originated in the business world and of which the general concepts are presented here, has given us a keener understanding of the diverse processes involved, their costs and how these costs are arrived at. Moreover, this method has identified the proportion of costs imputable to diagnostic work and of those linked to work specific to a university hospital, in particular teaching and research and development. The results can then be used for a clearer analysis of the figures required by prescribers and health care funding agencies, and, within the department, to enhance perception of work carried out by the entire staff in order to initiate a new type of management centered on activity (Activity-Based Management). Adaptable to any medical department, whatever its organizational structure, independent of the significance of any given code letter and regardless of the rating method used to grade activities, the ABC method also allows for comparisons between structures of a similar nature. The thoughts it inspires on economic performance must take into account the rules of good medical practice, the imperatives of quality assurance, the need for "breathing space" which are indispensable to research and a humanist conception of working relations.

A left pleural effusion with a calcified tumoral mass and left hemithoracic uptake on bone scan.

Diffuse malignant pleural mesothelioma is a rare primary tumor of the pleura with three principal histological types, epithelial; mesenchymal and mixed epithelial and mesenchymal. We report here a case of a mesenchymal mesothelioma with foci of osteosarcomatous degeneration revealed by dense calcifications associated with the pleural effusion on the computed tomography (CT) of the thorax. The bone scan revealed extraosseous uptake corresponding to the left pleura.

The value of immunohistochemistry in the differential diagnosis of endometrial carcinomas.

Endometrial carcinomas may originate from endometrial glandular epithelium and show endometrial differentiation, or from various types of metaplasias developing in the endometrium from pluripotent Müllerian epithelium. They then show endocervical or serous papillary differentiation. Because of their differences in spread, speed of growth and survival rates, it is important to subclassify these endometrial carcinomas. Immunohistochemically, adenocarcinoma with endometrial differentiation including adenoacanthomas and adenosquamous carcinomas can be recognized by their coexpression of cytokeratin 8 and vimentin, and by their negative reaction for CEA. Distinction from adenocarcinomas with mucinous differentiation, including mucoepidermoid adenocarcinomas, is possible by their negative reaction for vimentin and by their positive reaction for CEA. On the other hand, carcinomas with mucinous differentiation primarily located in the endometrium can not be distinguished from those primarily located in the endocervix by immunohistochemistry; that distinction must be made topographically. The same holds true for clear cell carcinomas of both locations. Over the past decade, mucinous adenocarcinomas and clear cell carcinomas originating from the endometrium have increased, whereas adenocarcinomas with endometrial differentiation have become less frequent. This shift is closely related to the altered postmenopausal hormone substitution with the addition of the synthetic gestagens. These apparently stimulate proliferation of endocervical epithelium not only in the endocervix, but also that arising in endocervical metaplasias of the endometrium.

[Role of steroid hormones and related biological substances in the etiology of endometrial carcinomas]. / Stellenwert der Steroidhormone und biologisch verwandter Substanzen in der Atiologie des Endometriumcarcinoms.

Synthetical oestrogens, as well as gestagens may cause metaplastic changes of the endometrial epithelia. While squamous and tubal metaplasia are most often due to oestrogenic stimulation and develop in hyperplastic endometria, mucinous and clear cell metaplasia are stimulated by gestagens and tamoxifen. Tamoxifen seems to act gestagen-like on the endometrium. We present data of 31 patients, who were treated with tamoxifen for breast cancer disease. 3 of these 31 developed endometrial adenocarcinoma.