This study identified two LAMN subtypes. Type II lesions have pathological features of increased risk for dissemination and should be considered for risk-reducing cytoreductive surgery.
Background:Degradation and chemical modification of RNA in formalin-fixed paraffin-embedded (FFPE) samples hamper their use in expression profiling studies. This study aimed to show that useful information can be obtained by Exon-array profiling archival FFPE tumour samples.Methods:Nineteen cervical squamous cell carcinoma (SCC) and 9 adenocarcinoma (AC) FFPE samples (10–16-year-old) were profiled using Affymetrix Exon arrays. The gene signature derived was tested on a fresh-frozen non-small cell lung cancer (NSCLC) series. Exploration of biological networks involved gene set enrichment analysis (GSEA). Differential gene expression was confirmed using Quantigene, a multiplex bead-based alternative to qRT–PCR.Results:In all, 1062 genes were higher in SCC vs AC, and 155 genes higher in AC. The 1217-gene signature correctly separated 58 NSCLC into SCC and AC. A gene network centered on hepatic nuclear factor and GATA6 was identified in AC, suggesting a role in glandular cell differentiation of the cervix. Quantigene analysis of the top 26 differentially expressed genes correctly partitioned cervix samples as SCC or AC.Conclusion:FFPE samples can be profiled using Exon arrays to derive gene expression signatures that are sufficiently robust to be applied to independent data sets, identify novel biology and design assays for independent platform validation.
Metastatic renal cancer remains hard to treat and the treatment is generally palliative. However, high-dose interleukin-2 (HD IL-2) produced 5% to 10% complete remissions and most of these were durable. With the advent of newer treatments with less toxicity, the role of HD IL-2 is uncertain. We present here a case series of 72 patients with metastatic renal cancer given first-line treatment with HD IL-2. From 2003 to 2006, the patients were offered treatment with HD IL-2 irrespective of their histologic features (retrospective cohort). From 2006 to 2008, the treatment was only offered to patients after stratification into risk groups based on histologic criteria (prospective cohort). In the early series, the response rate to HD IL-2 was 27% (8/30), but with prospective stratification of patients by histology the response rate was 52% (21/40) in the group with favorable histologic features. Combining outcome for all patients with the favorable histology (including those identified retrospectively) 49% (28/57) responded with 25% (14/57) achieving a complete remission and these seem durable. Patients with metastatic renal cancer should be carefully assessed for their suitability to undergo treatment with first-line systemic therapy with HD IL-2 as in carefully selected patients it has a high-rate response and durable remissions.
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