Profiling of VEGFs and VEGFRs as Prognostic Factors in Soft Tissue Sarcoma: VEGFR-3 Is an Independent Predictor of Poor Prognosis

BACKGROUND: In non-gastrointestinal stromal tumor soft tissue sarcoma (non-GIST STS) optimal treatment is surgery with wide resection margins. Vascular endothelial growth factors (VEGFs) and receptors (VEGFRs) are known to be key players in the initiation of angiogenesis and lymphangiogenesis. This study investigates the prognostic impact of VEGFs and VEGFRs in non-GIST STS with wide and non-wide resection margins. METHODS: Tumor samples from 249 patients with non-GIST STS were obtained and tissue microarrays were constructed for each specimen. Immunohistochemistry was used to evaluate the expressions of VEGF-A, -C and -D and VEGFR-1, -2 and -3. RESULTS: In the univariate analyses, VEGF-A (P=0.040) in the total material, and VEGF-A (P=0.018), VEGF-C (P=0.025) and VEGFR-3 (P=0.027) in the subgroup with wide resection margins, were significant negative prognostic indicators of disease-specific survival (DSS). In the multivariate analysis, high expression of VEGFR-3 (P=0.042, HR=1.907, 95% CI 1.024-3.549) was an independent significant negative prognostic marker for DSS among patients with wide resection margins. CONCLUSION: VEGFR-3 is a strong and independent negative prognostic marker for non-GIST STSs with wide resection margins

Fibroblast growth factor 2 orchestrates angiogenic networking in non-GIST STS patients

<p>Abstract</p> <p>Background</p> <p>Non-gastrointestinal stromal tumor soft-tissue sarcomas (non-GIST STSs) constitute a heterogeneous group of tumors with poor prognosis. Fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor-1 (FGFR-1), in close interplay with platelet-derived growth factor-B (PDGF-B) and vascular endothelial growth factor receptor-3 (VEGFR-3), are strongly involved in angiogenesis. This study investigates the prognostic impact of FGF2 and FGFR-1 and explores the impact of their co-expression with PDGF-B and VEGFR-3 in widely resected tumors from non-GIST STS patients.</p> <p>Methods</p> <p>Tumor samples from 108 non-GIST STS patients were obtained and tissue microarrays were constructed for each specimen. Immunohistochemistry was used to evaluate the expressions of FGF-2, FGFR-1, PDGF-B and VEGFR-3.</p> <p>Results</p> <p>In the multivariate analysis, high expression of FGF2 (P = 0.024, HR = 2.2, 95% CI 1.1-4.4) and the co-expressions of FGF2 & PDGF-B (overall; P = 0.007, intermediate; P = 0.013, HR = 3.6, 95% CI = 1.3-9.7, high; P = 0.002, HR = 6.0, 95% CI = 2.0-18.1) and FGF2 & VEGFR-3 (overall; P = 0.050, intermediate; P = 0.058, HR = 2.0, 95% CI = 0.98-4.1, high; P = 0.028, HR = 2.6, 95% CI = 1.1-6.0) were significant independent prognostic indicators of poor disease-specific survival.</p> <p>Conclusion</p> <p>FGF2, alone or in co-expression with PDGF-B and VEGFR-3, is a significant independent negative prognosticator in widely resected non-GIST STS patients.</p

Prognostic Impacts of Hypoxic Markers in Soft Tissue Sarcoma

Background. We aimed to explore the prognostic impact of the hypoxia-induced factors (HIFαs) 1 and 2, the metabolic HIF-regulated glucose transporter GLUT-1, and carbonic anhydrase IX (CAIX) in non-gastrointestinal stromal tumor soft tissue sarcomas (non-GIST STS). Methods. Duplicate cores with viable tumor tissue from 206 patients with non-GIST STS were obtained and tissue microarrays were constructed. Immunohistochemistry (IHC) was used to evaluate expression of hypoxic markers. Results. In univariate analyses, GLUT-1 (P < 0.001) and HIF-2α (P = 0.032) expression correlated significantly with a poor disease-specific survival (DSS). In the multivariate analysis, however, only high expression of GLUT-1 (HR 1.7, CI 95% 1.1–2.7, P = 0.021) was a significant independent prognostic indicator of poor DSS. Conclusion. GLUT-1 is a significant independent negative prognostic factor in non-GIST STS

Prognostic impact of peritumoral lymphocyte infiltration in soft tissue sarcomas

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to clarify the prognostic significance of peritumoral lymphocyte infiltration in the capsule of soft tissue sarcomas (STS). Multiple observations in preclinical and clinical studies have shown that the immune system has a role in controlling tumor growth and progression. Prognostic markers in potentially curable STS should guide therapy after surgical resection. The immune status at the time of resection may be important, but the prognostic significance of peritumoral lymphocytes is unknown.</p> <p>Methods</p> <p>Tissue microarrays from 80 patients with STS were constructed from duplicate cores of tissue from the tumor and the peritumoral capsule. Immunohistochemistry was used to evaluate the CD3+, CD4+, CD8+ and CD20+ lymphocytes in the tumor and the peritumoral capsule.</p> <p>Results</p> <p>In univariate analyses, increasing numbers of CD20+ (<it>P </it>= 0.032) peritumoral lymphocytes were associated with a reduced disease free survival (DSS). In multivariate analyses, a high number of CD20+ peritumoral lymphocytes (<it>P </it>= 0.030) in the capsule was an independent negative prognostic factor for DSS. There were no such associations of lymphocyte infiltration in the tumor.</p> <p>Conclusions</p> <p>A high density of CD20+ peritumoral lymphocytes is an independent negative prognostic indicator for patients with STS. Further research is needed to determine whether CD20 cells in the peritumoral capsule of STS may promote tumor invasion in the surrounding tissue and increase the metastatic potential.</p

A four-surface schematic eye of macaque monkey obtained by an optical method

AbstractSchematic eyes for four Macaca fascicularis monkeys were constructed from measurements of the positions and curvatures of the anterior and posterior surfaces of the cornea and lens. All of these measurements were obtained from Scheimpflug photography through the use of a ray-tracing analysis. Some of these measurements were also checked (and confirmed) by keratometry and ultrasound. Gaussian lens equations were applied to the measured dimensions of each individual eye in order to construct schematic eyes. The mean total power predicted by the schematic eyes agreed closely with independent measurements based on retinoscopy and ultrasound results, 74.2 ± 1.3 (SEM) vs 74.7 ± 0.3 (SEM) diopters. The predicted magnification of 202 μm/deg in one eye was confirmed by direct measurement of 205 μm/deg for a foveal laser lesion. The mean foveal retinal magnification calculated for our eight schematic eyes was 211 ± (SEM) μm/deg, slightly less than the value obtained by application of the method of Rolls and Cowey [Experimental Brain Research, 10, 298–310 (1970)] to our eight eyes but just 4% more than the value obtained by application of the method of Perry and Cowey [Vision Research, 12, 1795–1810 (1985)]

The prognostic impact of Akt isoforms, PI3K and PTEN related to female steroid hormone receptors in soft tissue sarcomas

Abstract Background The PI3K/Akt pathway is involved in cellular survival pathways by inhibiting apoptotic processes and stimulating cell growth and proliferation. Its negative prognostic value has been proven in many types of cancer. In soft tissue sarcomas, the expression profiles of the PI3K/Akt pathway components are poorly defined and their significance uncertain. We aimed to investigate the prognostic impact of Akt (Akt1) phosphorylated at threonine308 and serine473, Akt2, Akt3, PI3K and PTEN, alone and in coexpression with ER and PgR in non-gastrointestinal stromal tumor soft tissue sarcomas (non-GIST STSs). Patients and methods Tumor samples and clinical data from 249 patients with non-GIST STS were obtained, and tissue microarrays (TMAs) were constructed. Immunohistochemistry (IHC) was used to evaluate marker expression in tumor cells. Results In univariate analyses, the expression levels of p-Akt Thr308 (P = 0.002), Akt2 (P = 0.008) and PI3K (P 308 expression had strong unfavorable effect in men only (P = 0.009). In contrast, p-Akt Ser473 expression had strong unfavorable impact in women (P = 0.023). PgR-/p-Akt Ser473+ phenotype tended to have less favorable impact in women (P = 0.087), but was the most favorable one in men (P = 0.010). Conclusion Expression of PI3K was significantly associated with aggressive behavior and shorter DSS in non-GIST STSs. The site of Akt phosphorylation seems to have gender-dependent impact on survival in STS patients.</p