RESUMO
Abstract Objective Endometrial cancer (EC) is a heterogeneous disease with recurrence rates ranging from 15 to 20%. The discrimination of cases with a worse prognosis aims, in part, to reduce the length of surgical staging in cases with a better prognosis. This study aimed to evaluate the association between Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression and prognostic and morphological factors in EC. Methods This retrospective, cross-sectional, analytical study included 79 EC patients - 70 endometrioid carcinoma (EEC) and 9 serous carcinoma (SC) - and 74 benign endometrium controls. IMP3 expression was evaluated by immunohistochemistry-based TMA (Tissue Microarray), and the results were associated with morphological and prognostic factors, including claudins 3 and 4, estrogen and progesterone receptors, TP53, and KI67. Results IMP3 expression was significantly higher in SC compared to EEC in both extent (p<0.001) and intensity (p=0.044). It was also significantly associated with worse prognostic factors, including degree of differentiation (p=0.024, p<0.001), staging (p<0.001; p<0.001) and metastasis (p=0.002; p<0.001). IMP3 expression was also significant in extent (p=0.002) in endometrial tumors compared with controls. In addition, protein TP53 and KI67 showed significant associations in extent and intensity, respectively. Conclusion IMP3 expression was associated with worse prognostic factors studied. These findings suggest that IMP3 may be a potential biomarker for EC poorer prognosis.
RESUMO
Pilomyxoid astrocytomas (PMAs) manifest a more aggressive clinical course than pilocytic astrocytomas (PAs). Development of effective therapies demands a better biological understanding of PMA. We first conducted gene expression microarray analysis of 9 PMA and 13 PA from infra- and supratentorial sites. Unsupervised hierarchical clustering analysis demonstrated that tumors are grouped according to anatomic site, not diagnosis. Gene expression profiles were then contrasted between eight PMAs and six PAs, all supratentorial/hypothalamic/chiasmal. Clinical outcome of PMAs varied, with four out of four patients with diencephalic syndrome succumbing to disease, one of whom showed bulky metastatic leptomeningeal spread at autopsy, with bimodal maturation to PA in some areas and de-differentiation to glioblastoma in others. A surviving child has undergone multiple surgical debulking, with progressive maturation to PA over time. Ontology-enrichment analysis identified overexpression in PMAs of extracellular matrix and mitosis-related genes. Genes overexpressed in PMA vs. PA, ranked according to fold-change, included developmental genes H19, DACT2, extracellular matrix collagens (COL2A1; COL1A1) and IGF2BP3 (IMP3), the latter previously identified as an adverse prognostic factor in PMA and PA.