Identification of differentially expressed genes according to chemosensitivity in advanced ovarian serous adenocarcinomas: expression of GRIA2 predicts better survival.

BACKGROUND: The purpose of this study was to identify genes that are differentially expressed in chemosensitive serous papillary ovarian carcinomas relative to those expressed in chemoresistant tumours. METHODS: To identify novel candidate biomarkers, differences in gene expression were analysed in 26 stage IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14 chemoresistant tumours). We subsequently investigated the immunohistochemical expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas. RESULTS: Microarray analysis revealed a total of 57 genes that were differentially expressed in chemoresistant and chemosensitive tumours. Of the 57 genes, 39 genes were upregulated and 18 genes were downregulated in chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1, GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of GRIA2 was validated at the protein level by immunohistochemistry, and patients with GRIA2 expression showed a longer progression-free and overall survival (P=0.051 and P=0.031 respectively). CONCLUSIONS: We found 57 differentially expressed genes to distinguish between chemosensitive and chemoresistant tumours. We also demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma.

Malignant lymphoma of the central nervous system: difficult histologic diagnosis after glucocorticoid therapy prior to biopsy.

Four cases of central nervous system (CNS) lymphoma are reported which presented obstacles in diagnosis due to steroid treatment prior to biopsy. Reliable diagnoses were provided by molecular analysis. Malignant lymphoma of the CNS may be indistinguishable from other conditions, even in view of the gravity of the diagnosis. All patients had a previous history of glucocorticoid injection, for 2-18 days prior to stereotactic brain biopsy. The pathologic examination revealed in all cases axonal destruction and reactive gliosis with a variable infiltration of B- or T lymphocytes and macrophages. Characteristically, scattered degenerating small round cells with pyknotic or fragmented nuclei were also observed. However, the molecular assessment of paraffin-embedded tissues revealed the monoclonal IgH gene rearrangement, which allowed the confident diagnosis of B cell lymphoma. The histopathological findings of the present cases suggest that the tumor cells might be selectively destroyed by steroid treatment, which may render diagnosis impossible. Thus, molecular genetic investigation constitutes an important tool for establishing a diagnosis of CNS lymphoma obscured by steroid administration. This is especially true in cases where a paucity of tumor cells is observed or when monoclonality fails to be demonstrated by immunohistochemical tests.