Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including angiogenesis, cancer development, invasion and metastasis. The aim of the study was to analyze the expression of OPN in human astrocytomas and to correlate it with angiogenesis and patients' outcome. Seventy-six human astrocytomas including eight pilocytic astrocytomas (grade I), 10 diffuse astrocytomas (grade II), 8 anaplastic astrocytomas (grade III) and 50 glioblastomas (grade IV) were immunohistochemically stained for OPN protein. The distribution of OPN staining (cytoplasmic and/or interstitial) was assessed and compared to microvessel number and patients' survival. In normal brain tissue some glial and neuronal cells showed weak cytoplasmic staining, while interstitium was negative. Astrocytomas were heterogeneous regarding the OPN expression. High cytoplasmic OPN expression in glioblastomas was associated with poor patients' survival (p = 0.012). Also, we found the association of interstitial OPN expression and angiogenesis (p = 0.033), i.e. the number of newly formed blood vessels was higher in tumors showing high interstitial OPN expression. Our results indicate the overexpression of OPN protein in astrocytoma cells and suggest the role of OPN in astrocytoma progression and angiogenesis.

Background: The role of angiogenesis in the pathogenesis of renal cell carcinoma is well recognized, however, the influence of tumor cells in this activity has not yet been fully clarified. The aim of this study was to analyze the expression of hypoxia inducible factor-1α (HIF-1α), a regulatory factor of angiogenic switch, in comparison to vascular endothelial growth factor A and C (VEGF-A and VEGF-C), recognized to be involved in blood and lymph vessel neoangiogenesis, with potential association in the prognosis of patients with renal cell carcinoma.

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BackgroundThe role of epidermal growth factor (EGF) and its receptor (EGFR) in the pathogenesis and progression of various malignant tumors has long been known, but there is still disagreement concerning prognostic significance of EGFR expression in clear cell renal cell carcinoma (CCRCC). The present study was designed to analyze more objectively the protein EGFR expression in CCRCC and to compare its value with EGFR gene copy number changes and clinicopathologic characteristics including patient survival.MethodsThe protein EGFR expression was analyzed immunohistochemically on 94 CCRCC, and gene copy number alterations of EGFR by FISH analysis on 41 CCRCC selected according to distinct membrane EGFR staining.ResultsMembrane EGFR expression in tumor cells was heterogeneous with respect to the proportion of positive cells and staining intensity. FISH analysis did not reveal EGFR gene amplification, while polysomy of chromosome 7 found in 41% was associated with higher EGFR membrane expression. Moreover, EGFR overexpression was associated with a higher nuclear grade, larger tumor size and shorter patient's survival, while there was no connection with pathological stage.ConclusionIn conclusion, the protein expression of EGFR had an impact on prognosis in patients with CCRCC, while an increased copy number of chromosome 7 could be the possible reason for EGFR protein overexpression in the absence of gene amplification.

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Aim To assess the relationship between protein and messenger RNA (mRNA) levels of vascular endothelial growth factor (VEGF) and subcellular localization of nuclear factor-kappa B (NF-κB), proliferation rate of tumor cells, and clinicopathological characteristics of renal cell tumors.Methods We analyzed 31 one renal cell tumors -22 clear cell renal cell carcinomas (CCRCC) and 9 other histologic types (non-CCRCC). VEGF expression and subcellular localization of p65 member of NF-κB and Ki67 were immunohistochemically evaluated for the proliferation rate of tumor cells. Expression of VEGF mRNA was assessed using quantitative real-time polymerase chain reaction after total RNA extraction from snap-frozen tumor tissue samples.Results Cytoplasmic localization of VEGF protein in renal cell tumors showed a perimembranous and diffuse pattern, the former being more evident in CCRCC (27.1 ± 18.9 vs 3.3 ± 10 % tumors, P<0.001) and the latter in non-CCRCC type (71.7 ± 23.2 vs 31.1 ± 22.1 % tumors, P < 0.001). Heterogeneity in VEGF gene expression was more pronounced in CCRCC type than in non-CCRCC type (P = 0.004). In addition, perimembranous VEGF pattern was associated with higher VEGF mRNA levels (P = 0.006) and diffuse VEGF pattern with lower VEGF mRNA levels (P < 0.001). Nuclear and cytoplasmic staining of NF-κB/ p65 was observed in the majority of tumor cells. A significant association was recorded between cytoplasmic NK-κB/65 staining and VEGF staining of diffuse pattern (P = 0.026). Association between NF-κB/65 and proliferation rate of tumor cells was significant for cytoplasmic staining (P = 0.039) but not for nuclear NFkB/p65 staining (P = 0.099). ConclusionHigher but inhomogeneous expression of VEGF in tumor cells, especially in CCRCCs, is associated with NF-κB/65 activity. This indicates that both VEGF and NF-κB/65 may be important in renal carcinogenesis, representing a possible molecular target in the treatment of renal cell carcinoma.

Axillary lymph node dissection (ALND) is an important procedure in the staging of breast cancer patients. However, it is associated with a significant morbidity rate. In addition, using early diagnosis a high number of cases with negative lymph nodes can be identified. A lymph node defined as sentinel lymph node (SLN) would be the first to receive tumoral drainage. A less morbid but accurate staining procedure using mapping and SLN biopsy has been introduced. The aim of this study was to estimate the likelihood of additional disease in the axilla after SLN analysis. A total of 259 breast carcinomas and SLN biopsies followed by ALND were examined. The patient median age was 59 years, approximately 75% of them postmenopausal. Tumor size was 1.4 +/- 0.8 cm (almost 80% in pT1). SLNs were positive in 59 of 259 (22.8%) carcinomas, 30 (11.6%) with micrometastases (<2.0 mm) and 29 (11.2%) with metastases. Tumor size ( P = .004) and presence of lymphovascular invasion (LVI; P = .034) were found to be significant predictors of pathologically positive SLN. Following ALND, positive non-SLNs were present mostly in patients with metastasis >2 mm in SLN (P = .003), in carcinoma with higher nuclear grade ( P = .044), decreased estrogen receptor (ER; P = .042), and progesterone receptor (PR; P = .042). Finally, lymph node status (pN) following SLN and ALND was found to be significantly associated with tumor size ( P = .006), LVI (P = .037), PR (P = .023), and Her-2 status (P < .001). These results point to detailed analysis of primary tumor and SLN that may increase the precision of patient selection for further axillary surgery or radiotherapy.