18F-FPRGD2 PET/CT imaging of integrin αvß3 in renal carcinomas: correlation with histopathology.

UNLABELLED: This study aimed to correlate (18)F-FB-mini-PEG-E[c(RGDyK)](2) ((18)F-FPRGD2) uptake to integrin αvß3 expression and angiogenesis in renal tumors. METHODS: (18)F-FPRGD2 PET/CT was performed on 27 patients before surgical resection (median 4 d) of a renal mass. The (18)F-FPRGD2 uptake was compared with integrin αvß3, CD31, CD105, and Ki-67 using immunohistochemistry; with placental growth factor and vascular endothelial growth factor receptors 1 and 2 using reverse transcription polymerase chain reaction; and with vascular endothelial growth factor A isoforms using enzyme-linked immunosorbent assay. RESULTS: Overall, (18)F-FPRGD2 uptake significantly correlated (P < 0.0001) with integrin αvß3 expression in renal masses. However, it correlated only with integrin αvß3-positive vessels in the group of papillary carcinomas whereas it correlated with integrin αvß3 expression by tumor cells in the clear cell carcinoma group. CONCLUSION: (18)F-FPRGD2 uptake reflects the expression of integrin αvß3 in renal tumors but represents angiogenesis only when tumor cells do not express the integrin.

Expression of dentin sialophosphoprotein in human prostate cancer and its correlation with tumor aggressiveness.

Recent studies have demonstrated that two SIBLING family members, bone sialoprotein (BSP) and osteopontin (OPN), are overexpressed in human prostate cancer. The expression of these proteins is associated with the acquisition of a metastatic phenotype by cancer cells and a poor prognosis for the patient. Dentin sialophosphoprotein (DSPP) shares several structural and genetic features with OPN and BSP. The presence of DSPP has been recently established in salivary glands, indicating that its expression is not restricted to mineralized tissues. However, its potential expression in human tumors has not been addressed yet. In this study, we sought to evaluate the expression of DSPP in human prostate cancer. Immunohistochemistry was performed on 69 prostate cancer specimens using LFMb-21 anti-DSPP monoclonal antibody. All of the prostate cancer lesions examined expressed detectable levels of DSPP, as compared with no or low level of expression in adjacent normal glands (p < 0.0001). High grade prostatic intraepithelial neoplasia (HGPIN) glands generally displayed DSPP expression levels that were similar to those found in neighboring cancer glands. DSPP expression was significantly associated with the pathological stage (p = 0.0087) and the Gleason score (p = 0.0176) of the tumors. Western Blot was performed on 5 representative prostate tumor extracts and 3 prostatic tumor cell lines (PC3, LNCaP and DU145). All tumor extracts and cell lines analyzed have been found to express DSPP. In addition, in situ hybridization was used to assess the presence of DSPP mRNA. DSPP was detected at the RNA level in both HGPIN and tumoral glands. This study shows for the first time that DSPP is ectopically expressed in human prostate cancer. The expression of this SIBLING protein strongly correlates with conventional histopathological prognostic indicators of prostate cancer progression.