Expression of Molecular Markers in the Tumor and Survival Prognosis in Osteosarcoma

Abstract

Immunohistochemical study of p53, VEGF, Flt-1/VEGFR1 Ab-1, EGFR, HER-2/neu, Bax, and Cox-2 expression in osteosarcomas was carried out in 40 patients aged 16-70 years. Expression of p53 was detected in 27.5% tumors, VEGF in 15%, Flt-1/VEGFR1 Ab-1 in 97.5%, EGFR in 52.5%, HER-2/neu in 32.5%, Bax in 77.8%, and Cox-2 in 32.3% tumors. Multifactorial analysis showed that the expression of HER-2/neu (p=0.004), p53 (p=0.01), and Cox-2 (p=0.04) in osteosarcomas significantly correlated with unfavorable prognosis for overall survival, while HER-2/neu (p=0.02) and Cox-2 (p=0.003) with relapse-free survival. Analysis of HER-2/neu, p53, and Cox-2 expression in the primary tumor should be taken into consideration in the treatment of patients with osteosarcoma.

Anti-EGFR Antibody Cetuximab Enhances the Cytolytic Activity of Natural Killer Cells toward Osteosarcoma

“…In this study, we sought to explore whether this cytolytic activity can be more specifically targeted toward sarcoma cells using a sarcomareactive mAb, with a human Fc portion that can bind to FcRIIIa/CD16 on human NK cells. As several studies have described surface EGFR expression in osteosarcoma tumors and on osteosarcoma cell lines (12,19,(28)(29)(30)(31), we explored the potential of the anti-EGFR mAb cetuximab to specifically direct NK cell-mediated killing to sarcoma cell lines.…”

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

“…With the exception of osteosarcoma [272][273][274][275][276][277][278][279][280][281][282][283][284][285][286][287], synovial sarcoma [287][288][289][290][291], rhabdomyosarcoma [292][293][294], carcinosarcoma, and mixed Müllerian tumors, the latter two originating in the gynecologic tract that will be discussed below, there is no consistent evidence of HER2/neu expression or overexpression in the common soft tissue sarcomas [295][296][297][298][299][300][301][302][303][304]. HER2/neu is overexpressed in >40% of osteosarcomas [275,305], but is not a valid target in Ewings sarcoma [299,304,306] (consistent with the data above pertaining to lack of HER2/neu expression or overexpression in peripheral neuroendocrine tissues and tumors), chondrosarcomas or desmoid tumors [307].…”

The prognostic value of elevated vascular endothelial growth factor in patients with osteosarcoma: a meta-analysis and systemic review

“…We excluded 163 articles that did not meet the selection criteria. Figure 1 showed a Xow diagram of the selection process for relevant studies, and eleven papers were Wnally considered to be eligible for inclusion in our analysis (Lee et al 1999;Handa et al 2000;Kaya et al 2000Kaya et al , 2009Jung et al 2005;Charity et al 2006;Ek et al 2006;Oda et al 2006;Abdeen et al 2009;Boulytcheva et al 2010;Zhou et al 2011). …”

“…All the investigations tested the overall VEGF expression but not the VEGF isoforms, except that Lee focused his research on VEGF165 (Lee et al 1999). The studies conducted by Abdeen et al (2009), Ek et al (2006, Boulytcheva et al (2010), Zhou et al (2011) and Handa et al (2000) did not provide the 5-year survival of patients in VEGF+ and VEGF¡ subgroup, so they were not put into the aggregation process of meta-analysis but were included in the univariate analysis as they reported insigniWcant diVerence in survival of patients with diVerent VEGF levels to exclude possible information bias. Biopsies in all patients were conducted before any treatment were given except those in 2 papers written by Zhou and Charity, which may cause signiWcant osteosarcoma tissue necrosis and interfere with normal cellular function, rendering IHC analysis useless in most cases.…”

“…Alternative splicing of the VEGF gene can generate Wve isoforms of VEGFA (VEGF121, VEGF145, VEGF165, VEGF189, VEGF206), which possess somewhat variate biological functions including promoting endothelial cell growth, migration, mitosis and survival (Ferrara and Davis-Smyth 1997;Ho and Kuo 2007). Several studies have tried to investigate the clinical signiWcance of VEGF overexpression in the primary site of osteosarcoma patients and its correlation with the metastatic rates, as well as the prognosis, but no consensus on this has been reached, diVerent laboratories have yielded conXicting results (Lee et al 1999;Handa et al 2000;Kaya et al 2000Kaya et al , 2009Jung et al 2005;Charity et al 2006;Ek et al 2006;Oda et al 2006;Abdeen et al 2009;Boulytcheva et al 2010;Zhou et al 2011). But whether diVerences in these literatures have been mostly due to their limitation of sample size or genuine heterogeneity is unknown.…”