Introduction: Mesothelin (MSLN) is overexpressed in several tumors including ovarian cancer and is the target of current trials. There is limited and conflicting data on MSLN prognostic impact in ovarian cancer. Methods: We performed a retrospective study on patients with high-grade serous ovarian cancer, analyzing MSLN expression by immunohistochemistry and examining the correlation of its expression to overall and progression-free survival. Correlations of expression of MSLN, CD8, and macrophage markers in different tumor compartments were also investigated. Results: Positive MSLN expression was detected in 55.1% of primary tumors and 51.5% of the metastases. MSLN expression was not correlated with survival. We observed a significant positive correlation (r = 0.34, p = 0.01) between MSLN expression in the metastatic site and CD11c expression in total tumor area and perivascular area in the primary tumor. Isabelle Magalhaes and Josefin Fernebro contributed equally to this work as joint first authors. Jonas Mattsson and Hanna Dahlstrand also contributed equally to this work.
A conclusive diagnosis of malignant mesothelioma (MM) can be based on effusion cytology using the guidelines for the cytopathologic diagnosis of epithelioid and mixed‐type MM. Briefly, the diagnosis is obtained when the mesothelial phenotype of malignant cells is established by ancillary techniques. This study is based on the comparison of the overall survival rates of patients with MM when diagnosed by effusion cytology, histopathology, or a combination of both. A total of 144 patients were diagnosed with epithelioid and mixed‐type pleural MM at Karolinska University Hospital between 2004 and 2013. The diagnosis was obtained by histopathology in 74 cases and by cytological examination of pleural effusion in 70 cases. In 29 of the latter cases, a diagnostic biopsy was obtained simultaneously. A total of 104 patients received chemotherapy. All diagnoses were supported by clinical findings, including computer tomography scans. The median time between first symptoms and diagnosis was similar for cytology and histopathology. However, a delay of more than 6 months after first symptoms was seen in many patients in the histopathology group, resulting in late onset of treatment. The overall survival and proportion of long‐term survival were significantly better for cases diagnosed by cytology. Similarly, a better survival, following a cytological diagnosis, was also seen in patients who were only provided the best supportive care. Accurate cytological diagnosis enables conclusive diagnosis of MM. Our finding enables the initiation of treatment as soon as the cytological diagnosis is established, avoiding further delay and deterioration of patient survival and possibilities for treatment.
The global incidence of malignant mesothelioma (MM) causes considerable disease burden, suffering and health care costs. Beside preventive measures and ban the use of asbestos, early diagnosis would largely improve the chance of curative treatment. Current histologic criteria, however, requiring presence of invasion in the surrounding fatty tissue fail to identify MM in sufficiently early stage. Unilateral accumulation of pleural effusion is one of the earliest clinical manifestations of MM that occurs in approximately 90% of the patients. Therapeutic thoracocenthesis is necessary to remove the fluid and to relieve patients' symptoms. This effusion is easily accessible and offers early and minimally invasive diagnosis by combining cytologywith immunologic, molecular-and biomarker analyses. Typically, the fluid is rich in malignant cells and cell groups, but incipient stages of the disease may be difficult to recognize as the malignant cells can be masked by presence of inflammatory or reactive mesothelial cells. Recurrent, hemorrhagic and cell rich effusion should always be suspicious for MM and adequately prepared and analyzed to provide necessary information for subsequent therapy. Importantly, early detection of MM by integrating cytology and molecular approaches has high sensitivity and positive predictive value and has a major impact on patient survival.Thus, a conclusive positive MM cytology should lead to treatment without delay. This review summarizes molecular and diagnostic criteria of MM diagnosis.
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