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: 3.13). 11/2010; 108(4):502-7. DOI: 10.1111/j.1464-410X.2010.09848.x
Source: PubMed

ABSTRACT 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.

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    ABSTRACT: BACKGROUND:The significance of lymphovascular invasion (LVI) remains controversial, and the association of LVI with biochemical relapse was investigated in men treated with radical prostatectomy according to pathological results.METHODS:Data from 1268 patients undergoing radical prostatectomy between 2000 and 2009 were retrospectively reviewed. Clinicopathological variables were compared between LVI-negative and LVI-positive patients. Multivariate analyses by Cox proportional hazard model and Kaplan-Meier method were performed to identify risk factors for biochemical relapse in all patients, patients with pT2N0 and pT2N0 negative resection margin (RM).RESULTS:LVI information was available in 1160 cases, and LVI was seen in 121 cases (10.4%). Clinicopathological variables were significantly worse in LVI-positive patients than in LVI-negative patients. On multivariate analyses, PSA⩾10 ng ml(-1), pathological Gleason score ⩾8, pathological T stage ⩾3, lymph node metastasis, positive RM and LVI were independent predictors for biochemical relapse in all patients. In patients with pT2N0, PSA⩾10 ng ml(-1), pathological Gleason score ⩾8, positive RM and LVI were independent predictors for biochemical relapse. In patients with pT2N0 negative RM, LVI and pathological Gleason score ⩾8 were independent predictors for biochemical relapse (LVI; hazard ratio 3.809, 95% confidence interval 1.900-7.635, P-value<0.001, Gleason score ⩾8; hazard ratio 2.189, 95% confidence interval 1.199-3.999, P-value=0.011). With a median follow-up of 50 months, 5-year biochemical relapse-free survival in patients with pT2N0 negative RM was 95.7% in those with negative LVI in comparison to 85.3% in those with positive LVI (P<0.001, log rank).CONCLUSIONS:LVI was consistently a significant predictor for biochemical relapse after radical prostatectomy in not only all patients but also in patients with pT2N0 and pT2N0 negative RM. These results strongly support the significance of LVI as a predictor for biochemical relapse.Prostate Cancer and Prostatic Disease advance online publication, 21 October 2014; doi:10.1038/pcan.2014.40.
    Prostate Cancer and Prostatic Diseases 10/2014; 18(1). DOI:10.1038/pcan.2014.40 · 2.83 Impact Factor
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    ABSTRACT: Background There is a worldwide debate involving clinicians, uropathologists as well as patients and their families on whether Gleason score 6 adenocarcinoma should be labelled as cancer.Case descriptionWe report a case of man diagnosed with biopsy Gleason score 6 acinar adenocarcinoma and classified as low risk (based on a PSA of 5 ng/mL and stage cT2a) whose radical prostatectomy specimen initially showed organ confined Gleason score 3¿+¿3¿=¿6, WHO nuclear grade 3, acinar adenocarcinoma with lymphovascular invasion and secondary deposit in a periprostatic lymph node. When deeper sections were cut to the point that almost all the slice present in the paraffin block was sectioned, a small tumor area (<5% of the whole tumor) of Gleason pattern 4 (poorly formed glands) was found in an extraprostatic position.Conclusion The epilogue was that the additional finding changed the final Gleason score to 3¿+¿3¿=¿6 with tertiary pattern 4 and the stage to pT3a.Virtual SlidesThe virtual slide(s) for this article can be found here:
    Diagnostic Pathology 10/2014; 9(1):190. DOI:10.1186/s13000-014-0190-z · 2.41 Impact Factor
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    ABSTRACT: Background 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. Methods 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. Results 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. Conclusions 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.
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