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Background: There remains a need to identify and validate biomarkers for predicting prostate cancer (CaP) outcomes using robust and routinely available pathology techniques to identify men at most risk of premature death due to prostate cancer. Previous immunohistochemical studies suggest the proliferation marker Ki67 might be a predictor of survival, independently of PSA and Gleason score. We performed a validation study of Ki67 as a marker of survival and disease progression and compared its performance against another candidate biomarker, DLX2, selected using artificial neural network analysis., Methods: A tissue microarray (TMA) was constructed from transurethral resected prostatectomy histology samples (n=192). Artificial neural network analysis was used to identify candidate markers conferring increased risk of death and metastasis in a public cDNA array. Immunohistochemical analysis of the TMA was carried out and univariate and multivariate tests performed to explore the association of tumour protein levels of Ki67 and DLX2 with time to death and metastasis., Results: Univariate analysis demonstrated Ki67 as predictive of CaP-specific survival (DSS; P=0.022), and both Ki67 (P=0.025) and DLX2 (P=0.001) as predictive of future metastases. Multivariate analysis demonstrated Ki67 as independent of PSA, Gleason score and D'Amico risk category for DSS (HR=2.436, P=0.029) and both Ki67 (HR=3.296, P=0.023) and DLX2 (HR=3.051, P=0.003) as independent for future metastases., Conclusions: High Ki67 expression is only present in 6.8% of CaP patients and is predictive of reduced survival and increased risk of metastasis, independent of PSA, Gleason score and D'Amico risk category. DLX2 is a novel marker of increased metastasis risk found in 73% patients and 8.2% showed co-expression with a high Ki67 score. Two cancer cell proliferation markers, Ki67 and DLX2, may be able to inform clinical decision-making when identifying patients for active surveillance.

RENCA-IL-2 (Murine Renal Cell Carcinoma transfected with murine IL-2 gene) cells were rejected by immunocompetent (but not T-cell deficient) Balb/c mice, which developed 'immunity' to subsequent parental RENCA tumour cell challenge. Splenocytes adoptively transferred this immunity. CD4(+)and CD8(+)T-lymphocytes prepared from the spleens of 'tumour immune' mice were evaluated for their ability to traffic into the tumour environment using an in vivo model that enables visualization of events within the microvasculature. RENCA cells were implanted into the mouse cremaster muscle and the trafficking of syngeneic lymphocyte subpopulations, derived from naive and 'immune' animals, into both the RENCA tumour and the surrounding normal cremaster muscle microcirculation was measured by in vivo microscopy. Fluorescently labelled CD4(+)and CD8(+)T lymphocytes taken from the spleens of naive mice or mice previously immunized with RENCA-IL-2 were injected systemically into tumour-bearer mice. Naive effector cells migrated to, and flowed through both the tumour and the normal microcirculation, with negligible adhesion. However we observed the selective recruitment, localization and arrest of immune CD4(+)and CD8(+)T lymphocytes (P< 0.05) into the tumour microcirculation, and in some instances the subsequent extravasation of cells into the tumour interstitium. Lymphocyte rolling by 'immune' CD4(+)and CD8(+)T-cells in the tumour microcirculation was greatly reduced, suggesting impaired adhesion molecule expression on the tumour endothelium. This study clearly demonstrates, by direct in vivo microscopy assessment, the localization of effector cells, CD4(+)and CD8(+)lymphocytes into tumours., (Copyright 2000 Cancer Research Campaign.)

In the present study we have confirmed that approximately one third of human colorectal carcinomas fail to express the HLA - A,B,C monomorphic determinant reactive with the W6/32 MAb, and 44% express class II HLA antigens as shown by reactivity with NFK-1 MAb. Reduced staining with the W6/32 MAb was not always associated with the loss of beta 2m. In addition, the expression of HLA-A2 and Bw4 class I specific haplotypes on normal colon epithelium and tumour biopsy tissue was assessed. All normal colonic epithelia stained positively with MAb against A2 and Bw4 antigens, but a loss of these determinants was shown on tumour biopsies from patients tissue typed for the respective specificities. Loss of the A2 haplotype was shown in 4 of 15 tumour tissue samples, and loss of Bw4 specificities in 5 out of 7 tissue samples. The failure to detect specific loci determinants was not necessarily associated with loss of reactivity with W6/32 MAb.