IGF-IR: A new prognostic biomarker for human glioblastoma

Glioblastomas (GBMs) are the most common malignant primary brain tumors in adults. These tumors are refractory to conventional treatment approaches including surgical resection, radiotherapy and chemotherapy. The insulin-like growth factor (IGF) system is a complex network that includes soluble ligands (IGFI and IGFII), cell surface transmembrane receptors (IGF-IR and IGF-IIR), and soluble high-affinity binding proteins (IGFBP-1 to IGFBP-6). Many studies have reported a role for the IGF system in the regulation of tumor cell biology. However, the role of the different actors of this system remains unclear in GBM. The present study aimed to investigate the potential prognostic value of both the IGF ligands (IGFI and IGFII) and receptors (IGF-IR and IGF-IIR) in a large cohort of human GBMs. Tissue microarray and image analysis were conducted to quantitatively analyze the immunohistochemical expression of these proteins in 218 human GBMs. Both IGF-IR and IGF-IIR were overexpressed in GBMs compared to normal brain (p<10-4 and p=0.002, respectively). Moreover, with regard to standard clinical factors, IGF-IR positivity was identified as an independent prognostic factor associated with shorter survival (p=0.016) and was associated with a less favorable response to temozolomide. In agreement with this latter result, we showed that the IGF-IR inhibitor NVP-AEW541 enhanced in vitro the chemosensitivity of a GBM cell line (U87) to temozolomide. In conclusion, this study suggests that IGF-IR could be an interesting target for GBM therapy

KRAS Mutation in Serous Borderline Tumor of the Testis: Report of a Case and Review of the Literature

Ovarian-like epithelial tumors of the testis, including serous borderline tumors, are rare entities. We report the case of a 60-year-old man with a left intratesticular mass who had a radical orchidectomy. Histologically, the tumor was identical to the ovarian counterpart showing a well-delineated cystic lesion characterized by intraluminal papillae. The papillae are lined by atypical cuboidal or ciliated cells and are associated with psammoma bodies. The tumor cells express cytokeratin 7 (CK7), cytokeratin 5-6 (CK5-6), cancer antigen 125 (CA125), estrogen (ER), progesterone (PR), Wilm’s tumor gene (WT1), paired box gene 8 (PAX8), Ber-EP4, and epithelial membrane antigen (EMA). The diagnosis of a serous borderline tumor of the testis was proposed. Mutation testing using next-generation sequencing showed a Q61K KRAS gene mutation. To the best of our knowledge, this is the second case report of a serous borderline tumor of the testis with a Q61K KRAS gene mutation

The Prognostic Value of the Combination of Low VEGFR-1 and High VEGFR-2 Expression in Endothelial Cells of Colorectal Cancer

Research on tumor angiogenesis has mainly focused on the vascular endothelial growth factor (VEGF) family and on methods to block its actions. However, reports on VEGF receptor (VEGFR) expression in tumor-associated endothelial cells (ECs) are limited. Thus, we evaluated VEGF, VEGFR-1 and VEGFR-2 expression in ECs of colorectal cancer (CRC) using immunohistochemistry. VEGF, VEGFR-1 and -2 expression in ECs was quantitatively evaluated by digital image analysis in a retrospective series of 204 tumor tissue samples and related to clinical variables. The data show that the VEGF, VEGFR-1 and VEGFR-2 expression in ECs is heterogeneous. Multivariate analysis including a set of clinicopathological variables reveals that high EC VEGFR-1 expression is an independent prognostic factor for overall survival (OS). The combination of low VEGFR-1 and high VEGFR-2 expression in ECs outperforms models integrating VEGFR-1 and VEGFR-2 as separate markers. Indeed, this VEGFR-1_VEGFR-2 combination is an independent negative prognostic factor for OS (p = 0.012) and metastasis-free survival (p = 0.007). In conclusion, this work illustrates the importance of studying the distribution of VEGF members in ECs of CRC. Interestingly, our preliminary data suggest that high VEGFR-1 and low VEGFR-2 expression in ECs appear to be involved in the progression of CRC, suggesting that targeting EC VEGFR-1 could offer novel opportunities for CRC treatment. However, a prospective validation study is needed