Prognostic Analysis of Protein Expression by Tissue Microarray in Osteosarcoma
K Suzuki, J Fukuoka, M Kanamori, T Yasuda, T Hori, T Kimura. University of Toyama, Toyama, Japan; Toyama University Hospital, Toyama, Japan
Background: Osteosarcoma (OS) is the most frequent primary malignant bone tumor in young adults and adolescents. Novel markers of lung metastasis and prognosis of OS have not been reported. The purpose of this study was to determine the expression and prognostic significance of proliferating cell nuclear antigen (PCNA), p-Smad2 as a downstream signal of TGF-b, vascular endothelial growth factor (VEGF) and podoplanin in OS.
Design: We constructed a tissue microarray (TMA) block composed of 23 cases, including samples from 21 biopsies, 23 surgical specimens, 5 lung metastases and 6 bone metastases. Immunohistochemical (IHC) staining was performed with four kinds of proteins: PCNA; p-Smad2; VEGF; and podoplanin. IHC score was determined as the sum of the distribution score (0, 1, or 2) and intensity score (0, 1, 2, or 3) of the staining signal. We assessed: 1) the relationship with IHC score and overall survival; 2) the difference in IHC score between primary and metastatic sites; 3) correlations with each IHC score for the four kinds of proteins in primary site using the Spearman's rank coefficient.
Results: 1) Mean and median durations of overall patient follow-up were 75.35 and 35 months, respectively (range, 0.15-300 months). The correlation between PCNA and survival rate was significant (log-rank 0.032). Overall survival rate was 23.5% for strongly PCNA-positive cases, compared with 100% for weakly PCNA-positive cases. 2) IHC scores for PCNA, VEGF and podoplanin were significantly higher at the metastatic site than at the primary site (p<0.01 each). Conversely, IHC score for p-Smad2 was higher at the primary site than metastatic site (p<0.01). 3) Significant correlations were seen between PCNA and podoplanin (p=0.039, r=0.440), p-Smad2 and podoplanin (p=0.007, r=0.568), p-Smad2 and VEGF (p=0.018, r=0.504) and between VEGF and podoplanin (p=0.040, r=0.438).
Conclusions: 1) Our survival analysis indicated that positive PCNA staining correlates significantly with prognosis in OS. PCNA is useful as a prognostic marker for OS. 2) Podoplanin was significantly expressed at metastatic sites, suggesting that podoplanin promotes hematogenous metastasis. 3) Expression of podoplanin is correlated with expression of PCNA, VEGF and p-Smad2, respectively. As a result, podoplanin may play a significant role in lung metastasis in cooperation with VEGF and TGF-b.
Category: Bone & Soft Tissue
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 17, Tuesday Morning