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We evaluated the association of cell adhesion molecule 4 ( CADM4) expression with clinicopathologic parameters and overall survival ( OS) in patients with small intestinal adenocarcinomas ( SIAs) and determined its prognostic significance. CADM4 immunohistochemical staining was performed for 170 SIA samples. Loss of or low CADM4 expression was observed in 26 (15.3%) and 50 (29.4%) cases, respectively, and it was significantly associated with undifferentiated histology (p < 0.044), high-grade tumor (p < 0.001), high pT3 or pT4 stage (p < 0.038), pancreatic invasion (p < 0.018), and lymphatic invasion (p < 0.020). Patients with CADM4 expression loss had significantly poorer OS (p < 0.042). On multivariate analysis, SIA in the jejunum and ileum, (hazard ratio [ HR], 2.465; 95% confidence interval [ CI], 1.288-4.720; p = 0.006 and HR, 3.407; 95% CI, 1.515-7.662; p = 0.003, respectively), signet ring cell carcinoma ( HR, 92.388; 95% CI, 14.813-576.230; p = 0.000), SIA with lymph node metastasis ( HR, 3.223; 95% CI, 1.697-6.124; p = 0.000), retroperitoneal seeding ( HR, 3.696; 95% CI, 1.303-10.479; p = 0.014), and CADM4 expression loss ( HR, 2.348; 95% CI, 1.130-4.882; p = 0.022) were associated with poor OS. CADM4 expression loss is an important prognostic marker for SIA. [ABSTRACT FROM AUTHOR]

Aim The vascular endothelial growth factor ( VEGF) or its family might play role in tumor-related angiogenesis in gastrointestinal stromal tumors ( GIST), thereby affecting the prognosis. Accordingly, the present study analyzed the impact of VEGF and VEGF receptor-2 ( VEGFR-2) gene polymorphisms on the prognosis for GIST patients. Methods In all, 213 consecutive patients with GIST from five medical centers were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tumor tissue, and four VEGF (−2578 C/ A, −1498 C/ T, −634 G/ C, and +936 C/ T) and one VEGFR-2 (+1416 A/ T) gene polymorphisms were determined using a Sequenom MassARRAY system. Results With a median follow up of 18.4 months, the estimated 5-year relapse-free survival and overall survival rates were 70 and 87%, respectively. In a multivariate analysis including age, sex, primary site of disease, pathology and risk stratification, no significant association was observed between the polymorphism of the VEGF and VEGFR-2 genes and survival. Conclusion None of the five VEGF and VEGFR-2 gene polymorphisms investigated in this study was found to be an independent prognostic marker for Korean patients with surgically resected GIST. However, further studies on a larger scale are warranted to clarify the role of VEGF and VEGFR gene polymorphisms as a prognostic biomarker for GIST patients. [ABSTRACT FROM AUTHOR]

Aims Invasive breast carcinoma ( IBC) with neuroendocrine ( NE) differentiation has been controversial in terms of its definition and clinical outcome. We investigated the incidence and clinical significance of NE differentiation in patients with IBC. Methods and results We performed immunohistochemistry for NE markers, chromogranin- A and synaptophysin on 1428 IBC samples using tissue microarrays and classified cases with NE differentiation into two groups, focal (1-49% tumour cells positive for any NE marker) and diffuse (≥50% tumour cells positive) groups. Fifty-nine cases (4.1%) showed NE differentiation immunohistochemically, and the majority did not show typical NE morphology. The presence of NE differentiation showed a significant association with positive oestrogen receptor ( P = 0.001) and progesterone receptor ( P = 0.008) status. Patients with NE differentiation showed worse overall survival ( OS) and disease-free survival ( DFS) than those without NE differentiation in both univariate ( P < 0.001 for both) and multivariate ( OS, P = 0.004; DFS, P < 0.001) analyses. Conclusions IBC with NE differentiation is a distinct subtype of mammary carcinoma with an aggressive clinical outcome. [ABSTRACT FROM AUTHOR]

Summary: Small intestinal adenocarcinoma is a rare malignant neoplasm, and its clinicopathologic characteristics have not been well elucidated. A total of 197 small intestinal adenocarcinoma cases were collected from 22 institutions in South Korea and were evaluated for clinicopathologic factors that affect the prognosis of small intestinal adenocarcinoma patients using univariate and multivariate analyses. The mean patient age was 59 years, and the male-to-female ratio was 1.7:1. Tumors were located in the duodenum of 108 cases (55%), the jejunum in 59 (30%), and the ileum in 30 (15%). Predisposing conditions were observed in 23 cases (12%), including 17 cases with sporadic adenomas, 3 with Peutz-Jeghers syndrome, 2 with Meckel diverticulum, and 1 with Crohn disease. Synchronous or metachronous malignant tumors were identified in 31 cases (16%), including 13 colorectal and 10 stomach cancers. About 90% of tumors were classified as either pT3 (63 cases) or pT4 (112 cases). The median survival time for all small intestinal adenocarcinoma patients was 39.7 months. Compared with small intestinal adenocarcinomas without accompanying sporadic adenomas, small intestinal adenocarcinomas with accompanying adenomas were more well differentiated (P < .0001), with a more polypoid growth pattern (P < .0001), a lower pT classification (P < .0001), less perineural invasion (P = .01), and less lymphatic invasion (P = .03). Small intestinal adenocarcinoma patients with associated sporadic adenomas (77%) had a significantly better 5-year survival rate than those without sporadic adenomas (38%, P = .02). By univariate analysis, small intestinal adenocarcinoma patients had significantly different survival based on pT classification (P = .003), lymph node metastasis (P < .0001), distal location (jejunal and ileal carcinomas) (P = .003), retroperitoneal tumor seeding (P < .0001), vascular invasion (P = .007), lymphatic invasion (P = .001), peritumoral dysplasia (P = .004), and radiation therapy (P = .006). By multivariate analysis, lymph node metastasis (P = .01) and distal location (P = .003) were independent predictors of a worse prognosis. In conclusion, (1) small intestinal adenocarcinomas are diagnosed at an advanced disease stage; therefore, the development of strategies for detection at an earlier stage is needed. (2) Small intestinal adenocarcinoma patients with an adenomatous component had a better survival than those without an adenomatous component. (3) Lymph node metastasis and distal location (jejunum and ileum) of tumor are the most important independent prognostic factors. [Copyright &y& Elsevier]