Osteopontin Expression and Its Prognostic Significances in Human Renal Cell Carcinoma

BACKGROUND: Osteopontin (OPN) is a glycoprotein and it participates in cell-cell and cell-matrix interactions. In vitro studies suggest that the OPN expression is associated with tumor metastasis, and especially with the metastasis of osteotropic tumors originating in breast, prostate and lungs. Since no human tissue study has suggested the means by which OPN participates in the tumorigenesis, angiogenesis, progression and metastasis of renal cell carcinoma (RCC), we evaluated the expression and prognostic significance of OPN in RCC. METHODS: Immunohistochemistry was performed with using the primary antibody for OPN on the archival paraffin-embedded tissue microarray specimens from 51 RCC patients who underwent radical or simple nephrectomy. RESULTS: In the normal kidney specimens, OPN was expressed in a few compressed distal tubules adjacent to the RCCs. In RCCs, the OPN expression was elevated in larger tumors (p<0.05) and in the tumor with low microvessel density (p<0.01). In the present study, univariate analysis indicated that stage, tumor size, lymph node and distant organ metastasis are significant prognostic factors for disease free survival (DFS) in RCC patients (p<0.01), but OPN is not (p=0.0661). Multivariate analysis indicated lymph node metastasis is the independent prognostic indicator of DFS (p<0.05). CONCLUSION: Though this study has statistical limitations, these results suggest OPN plays a role in tumor progression and metastasis and it may act as a potential prognostic indicator to predict the prognosis of RCC patients.

Expression of CD44 Isoforms and Its Significance in Renal Cell Carcinoma

Background : CD44 is a transmembranous glycoprotein that participates in cell-cell and cell-matrix interactions, and it also contributes to cell migration. In vitro studies have suggested that the expression of CD44 isoforms is associated with tumor metastasis. Since it is not clear whether the CD44 isoforms play a role in the tumorigenesis, differentiation, progression or metastasis of renal cell carcinomas (RCCs). Methods : We performed immunohistochemistry with primary antibodies for the standard CD44 (CD44s) and the CD44 variant exon 6 (CD44v6) on the archival paraffin-embedded tissue microarray (TMA) specimens from 51 RCC patients. Results : In the normal kidney, the expressions of both CD44s and CD44v6 were negligible. The CD44s expression was increased in accordance with the tumor size (p<0.01), but it was not related to the microvessel density (MVD). No CD44v6 expression was observed in all RCC cases. Univariate analysis indicated that stage, tumor size, lymph node metastasis and distant organ metastasis were the statistically significant prognostic factors for disease free survival (DFS) (p<0.01), and the multivariate analysis proved that stage (p<0.01) and tumor size (p<0.05) were the independent prognostic factors for DFS. Conclusions : Our results suggest that CD44s, but not CD44v6, plays a role in tumor progression and it could be a potential prognostic factor for patients with RCCs.

An Analysis for Angiotensin Converting Enzyme Gene Polymorphism in Formalin-fixed, Paraffin-embedded Tissues from Patients with Sarcoidosis

BACKGROUND: Sarcoidosis is a systemic disease characterized by nonnecrotizing granulomas involving the lung and hilar lymph nodes. Serum angiotensin converting enzyme (sACE) levelsin patients with sarcoidosis have been implicated as an indicator of granuloma burden.Recently, it has been found that ACE gene insertion/deletion (ID) polymorphism affects sACE levels in healthy individuals. Moreover, reported sACE levels were highest in the deletion/deletion(DD) genotype. Previous studies to investigate the distribution of ACE genotypes accordingto ethnic groups have revealed various results and have caused controversy. METHODS: Polymerase chain reactions were performed to determine the ACE genotypes in fifteen formalinfixed, paraffin-embedded tissues from patients with sarcoidosis. RESULTS: The distribution of ACE gene (I/D) polymorphism in patients with sarcoidosis was significantly different from that in normal controls. The DD genotype was more frequent in patients with sarcoidosis than in thenormal controls. The D allele frequency was also higher in patients with sarcoidosis than in thenormal controls. The relative risk of sarcoidosis was higher in DD homozygotes. CONCLUSIONS: These results suggested the ACE gene I/D polymorphism may play an important rolein the pathogenesis and progression of sarcoidosis.