Prognostic significance of lymphovascular invasion in radical prostatectomy specimens
Urology Service, Department of Surgery, Health Outcomes Research Group, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. BJU International
(Impact Factor: 3.53).
11/2010; 108(4):502-7. DOI: 10.1111/j.1464-410X.2010.09848.x
OBJECTIVES To determine whether lymphovascular invasion (LVI) in radical prostatectomy (RP) specimens has prognostic significance. The study examined whether LVI is associated with clinicopathological characteristics and biochemical recurrence (BCR). PATIENTS AND METHODS LVI was evaluated based on routine pathology reports on 1298 patients treated with RP for clinically localized prostate cancer between 2004 and 2007. LVI was defined as the unequivocal presence of tumour cells within an endothelium-lined space. The association between LVI and clinicopathological features was assessed with univariate logistic regression. Cox regression was used to test the association between LVI and BCR. RESULTS LVI was identified in 10% (129/1298) of patients. The presence of LVI increased with advancing pathological stage: 2% (20/820) in pT2N0 patients, 16% (58/363) in pT3N0 patients and 17% (2/12) in pT4N0 patients; and was highest in patients with pN1 disease (52%; 49/94). Univariate analysis showed an association between LVI and higher preoperative prostate-specific antigen levels and Gleason scores, and a greater likelihood of extraprostatic extension, seminal vesicle invasion, lymph node metastasis and positive surgical margins (all P < 0.001). With a median follow- up of 27 months, LVI was significantly associated with an increased risk of BCR after RP on univariate (P < 0.001) and multivariate analysis (hazard ratio, 1.77; 95% confidence interval, 1.11-2.82; P = 0.017). As a result of the relatively short follow- up, the predictive accuracy of the standard clinicopathological features was high (concordance index, 0.880), and inclusion of LVI only marginally improved the predictive accuracy (0.884). CONCLUSIONS Although associated with features of aggressive disease and BCR, LVI added minimally to established predictors on short follow-up. Further study of cohorts with longer follow-up is warranted to help determine its prognostic significance.
Available from: Diane R Bielenberg
- "However, the presence of tumor-positive lymph nodes continues to be an important predictor of distant metastases and patient survival in many cancers [9,26]. Studies have shown that lymphovascular invasion is significantly associated with PSA biochemical recurrence and patient survival in prostate cancer [5,27], although LVI may not significantly improve predictive accuracy above standard clinicopathological features in prostate cancer . We clearly observed tumor foci in the enlarged lymphatics of the DU145-LN4 orthotopic tumors, indicating that our model recapitulates steps common in human prostate cancer progression. "
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Understanding the complex, multistep process of metastasis remains a major challenge in cancer research. Metastasis models can reveal insights in tumor development and progression and provide tools to test new intervention strategies.
To develop a new cancer metastasis model, we used DU145 human prostate cancer cells and performed repeated rounds of orthotopic prostate injection and selection of subsequent lymph node metastases. Tumor growth, metastasis, cell migration and invasion were analyzed. Microarray analysis was used to identify cell migration- and cancer-related genes correlating with metastasis. Selected genes were silenced using siRNA, and their roles in cell migration and invasion were determined in transwell migration and Matrigel invasion assays.
Our in vivo cycling strategy created cell lines with dramatically increased tumorigenesis and increased ability to colonize lymph nodes (DU145LN1-LN4). Prostate tumor xenografts displayed increased vascularization, enlarged podoplanin-positive lymphatic vessels and invasive margins. Microarray analysis revealed gene expression profiles that correlated with metastatic potential. Using gene network analysis we selected 3 significantly upregulated cell movement and cancer related genes for further analysis: EPCAM (epithelial cell adhesion molecule), ITGB4 (integrin β4) and PLAU (urokinase-type plasminogen activator (uPA)). These genes all showed increased protein expression in the more metastatic DU145-LN4 cells compared to the parental DU145. SiRNA knockdown of EpCAM, integrin-β4 or uPA all significantly reduced cell migration in DU145-LN4 cells. In contrast, only uPA siRNA inhibited cell invasion into Matrigel. This role of uPA in cell invasion was confirmed using the uPA inhibitors, amiloride and UK122.
Our approach has identified genes required for the migration and invasion of metastatic tumor cells, and we propose that our new in vivo model system will be a powerful tool to interrogate the metastatic cascade in prostate cancer.
Available from: Björn L.D.M. Brücher
- "In fact, >50% of patients with positive nodes demonstrated LVI. In multi-variate analysis, the presence of LVI was minimally helpful; the authors suspected that follow-up was too short for an additional variable to contribute much to accuracy of estimating prognosis over that provided by standard pathologic features 64. "
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ABSTRACT: Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm in men in the United States and the second leading cause of cancer mortality. One in 7 men will be diagnosed with prostate cancer during their lifetime. As a result, monitoring treatment response is of vital importance. The cornerstone of current approaches in monitoring treatment response remains the prostate-specific antigen (PSA). However, with the limitations of PSA come challenges in our ability to monitor treatment success. Defining PSA response is different depending on the individual treatment rendered potentially making it difficult for those not trained in urologic oncology to understand. Furthermore, standard treatment response criteria do not apply to prostate cancer further complicating the issue of treatment response. Historically, prostate cancer has been difficult to image and no single modality has been consistently relied upon to measure treatment response. However, with newer imaging modalities and advances in our understanding and utilization of specific biomarkers, the future for monitoring treatment response in prostate cancer looks bright.
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