IL-6, IL-10 and HSP-90 expression in tissue microarrays from human prostate cancer assessed by computer-assisted image analysis.

The interleukins (IL)-6 and -10 and heat shock proteins (HSP) have an important role in the host-tumor interaction and in tumor bulk. HSP-90 may have a regulatory role in cytokine biosynthesis and prognostic value in some tumors. To define the role of IL-6, IL-10 and HSP-90 in prostate cancer progression the immunohistochemical expressions of these proteins were analyzed in 168 prostatic carcinomas. IL-6, IL-10 and HSP-90 immunoreactivity was higher in prostatic carcinoma (CaP) and intra-epithelial prostatic neoplasia (PIN) than in normal prostatic tissue (NAP) adjacent to neoplasia. In the epithelium, IL-6, IL-10 and HSP-90 expressions increased from NAP to PIN to CaP. In the stroma, IL-6 and IL-10 expressions decreased significantly from NAP to PIN to CaP (p < 0.01 by Chi-square test), while HSP-90 expression increased. In the epithelium of PIN and CaP, IL-6 immunoreactivity was significantly lower than IL-10 and HSP-90. In neoplastic acini HSP-90 levels were significantly higher than those of IL-6 and IL-10 (p < 0.01 by Chi-square test). In the stroma of NAP and PIN, but not of CaP, HSP-90 immunoreactivity was significantly lower than that of IL-6 and IL-10 (p < 0.01). Our results indicate that the IL-6 and IL-10 cytokine balance differs in pathological and normal prostate, thus suggesting that certain cytokines are specific to the neoplastic prostate. Changes in the expressions of IL-6, IL-10 and HSP-90 in human prostate carcinoma samples could be used as a prognostic marker of disease progression.

Quantitative immunohistochemical and in situ hybridization analysis of metalloproteinases in prostate cancer.

The role of matrix metalloproteinases (MMPs) as markers of tumor progression in prostate cancer (CaP) is complex and poorly understood. Using computerized image analysis, the differential expression of interstitial collagenase (MMP-1), gelatinase B (MMP-9), matrilysin-1 (MMP-7) and the membrane-type 1-MMP (MT1-MMP) in the epithelium and stroma of human prostate neoplastic tissues were investigated. Using immunohistochemistry and in situ hybridization techniques, 38 paraffin-embedded prostatic samples were analyzed and CaP was compared with prostate intraepithelial neoplasia (PIN) and its normal adjacent prostate (NAP) counterpart. The association of MMP protein and mRNA expression with Gleason histological tumor grade and TNM clinical stage was also determined. In most prostatectomy specimens examined, detectable amounts of MMP-1, MT1-MMP, MMP-7 and MMP-9 proteins and MT1-MMP and MMP-9 mRNA were found in the epithelial and stromal components of CaP, PIN and NAP. MMP expression was significantly stronger in the epithelium than in the stroma (p < 0.01). In the epithelium of normal and preneoplastic prostate tissue, MMP-1, MMP-9 and MT1-MMP were preferentially expressed in secretory luminal cells; conversely, MMP-7 was concentrated in basal cells. Epithelial and stromal expressions of MMPs differed in normal, preneoplastic and CaP tissues. Whereas MMP-1 was overexpressed in NAP epithelial glands and progressively decreased from PIN to CaP, MMP-7, MMP-9 and MT1-MMP were more strongly expressed in CaP than in PIN and NAP tissue. The MMPs investigated reached their highest levels in prostate tumors with high Gleason scores. The differential MMP expression in epithelial and stromal prostate tissue supports the previous hypothesis that MMPs may be autocrine and paracrine mediators of the stroma-epithelial interaction, an event that plays a critical role in regulating normal and abnormal prostate growth. MMP gene regulation changes during the early stage of prostate cancer. Differential expression of MMP components in CaP may reflect the malignant phenotype and more aggressive tumor behavior.

Can p503s, p504s and p510s gene expression in peripheral-blood be useful as a marker of prostatic cancer?

BACKGROUND: The aim of the study was to investigate whether p503S, p504S and p510S gene expression in peripheral-blood be useful as a diagnostic or prognostic marker of prostatic cancer. METHODS: Circulating cells were identified by reverse transcription-polymerase chain reaction (RT-PCR) to detect p503S, p504S and p510S mRNA in peripheral blood (PB) from 11 patients with treated prostatic carcinoma (CaP), 11 with newly-diagnosed untreated CaP and 20 with benign prostatic hyperplasia (BPH) (controls). RESULTS: RT-PCR amplified P503S in 7 of 11 untreated and 2 of 11 treated patients with CaP and 5 of 20 with BPH; p504S in 7 of 11 untreated and in 9 of 11 treated patients with CaP and 11 of 20 with BPH; whereas it amplified p510S in all subjects with CaP and in 15 of 20 with BPH. CONCLUSION: These findings suggest that the investigated genes are poorly specific and probably of little use as diagnostic or prognostic prostatic markers in peripheral blood for monitoring disease progression and recurrence.

Insulin-like growth factor (IGF)-I, IGF-II and IGF type I receptor (IGFR-I) expression in prostatic cancer.

Despite evidence implicating the insulin-like growth factor (IGF) system in the pathogenesis of prostate cancer, its precise role remains unclear. In this study we investigated the differential expression of IGF-I, IGF-II and their type I receptor (IGFR-I) in the epithelium and stroma of prostate neoplastic tissues. Using immunohistochemistry and in situ hybridization techniques, we analyzed 43 paraffin-embedded prostatic samples and compared prostatic cancer (Pca) with prostatic intraepithelial neoplasia (PIN) and its normal adjacent prostate (NAP) counterpart. We then determined a possible correlation of the immunohistochemical and in situ findings with two known prognostic clinical-pathological indices: Gleason score histological tumor grade and TNM clinical stage. In 22 of the 43 frozen prostatectomy specimens, IGF-I, IGF-II and IGFR-I mRNA expression were also evaluated by semiquantitative RT-PCR. Non neoplastic and neoplastic tissues examined contained detectable amounts of epithelial and stromal IGF-I, IGF-II and IGFR-I protein and mRNA; all levels increased significantly from normal tissue to PIN to Pca. In all three areas examined, IGFR-I expression was invariably higher in epithelium than in stroma, whereas expression of IGF ligands differed. In normal prostatic tissue, IGF-I and IGF-II expression was higher in stroma than in epithelium. Conversely, in Pca tissue, both factors were more strongly expressed in epithelial malignant cells. PIN areas showed IGF-I lowest, and IGF-II and IGFR-I levels highest in the epithelium. IGF-II protein and mRNA reached their highest levels in prostate tumors with high Gleason scores. These findings indicate that the IGF system changes as prostate tissue progresses from a normal to a malignant state. Differential expression of certain IGF system components in Pca may be associated with the malignant phenotype and more aggressive tumor behavior. Hence IGFs could serve to predict the outcome of prostatic cancer.

Is DD3 a new prostate-specific gene?

The search for new and more specific molecular markers of prostatic cancers has led, in recent years, to the identification of the DD3 gene. Using reverse transcription (RT)-PCR, we investigated DD3 gene expression in human cell lines, in blood samples from healthy men and women donors and in various neoplastic and non-neoplastic tissues from the prostate and other organs. Whereas RT-PCR analysis using primers that amplified the region spanning exons 1 and 3 yielded DD3 gene expression in all samples examined, a primer downstream to exon 4 detected the expected size DD3 band only in benign and malignant prostatic tissues. These findings indicate that the only prostate specific region of DD3 is exon 4.