Expression of insulin-like growth factor 1 and insulin-like growth factor 1 receptor is associated with the favorable clinicopathologic parameters in small intestinal carcinomas.

OBJECTIVE: The insulin-like growth factor (IGF) system has been known to play a critical role in tumor development and progression in many human cancers. However, the role of the IGF system in small intestinal carcinoma (SIC) has not been studied yet. METHODS: We evaluated the expression of IGF1 and IGF1 receptor (IFG1R) in a total of 194 cases of SIC. RESULTS: IGF1 expression was associated with well/moderate differentiation, better survival, lower pT, lower stage and no lymph node metastasis. IGF1R was more diffusely and strongly expressed in tumors with lower pT and lower stage. CONCLUSIONS: IGF1 and IGF1R expression is associated with favorable clinicopathologic parameters and may involve early carcinogenesis of SICs. Target therapy for the IGF1R signaling pathway may not have a major therapeutic role in treating SIC.

Multiplication of Chromosome 17 Centromere Is Associated with Prognosis in Patients with Invasive Breast Cancers Exhibiting Normal HER2 and TOP2A Status.

PURPOSE: This study aimed to investigate the clinical significance of chromosome 17 centromere (CEP17) multiplication (increased copy number of CEP17) related to human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) status in patients with invasive breast cancer. METHODS: We constructed tissue microarrays using 594 invasive breast cancer samples and performed single-color silver-enhanced in situ hybridization (SISH) assay for HER2, TOP2A, and CEP17 to assess for copy number aberrations. The association of CEP17 multiplication with patient survival was analyzed according to HER2 and TOP2A status. RESULTS: Among 567 informative cases, HER2 amplification was noted in 22.8%, TOP2A amplification in 8.3% and TOP2A deletion in 11.1%. CEP17 multiplication was identified in 33.2% and was significantly associated with worse overall survival (OS) (p=0.02) and disease-free survival (DFS) (p=0.02). CEP17 multiplication correlated with patient survival in patients with normal TOP2A or non-amplified HER2 status, but the prognostic significance was lost in those with altered TOP2A or amplified HER2. On multivariate analyses, CEP17 multiplication was an independent prognostic factor for poorer OS (p=0.02) and DFS (p=0.01) in patients with normal TOP2A and non-amplified HER2. CONCLUSION: CEP17 multiplication was identified as a promising prognostic marker in patients with invasive breast cancer exhibiting either non-amplified HER2 or normal TOP2A status.