Evaluation of metastatic potential of prostate cancer

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Evaluation of metastatic potential of prostate cancer Yoshitomo Chihara • Kiyohide Fujimoto Yoshihiko Hirao • Hiroki Kuniyasu



Received: 8 September 2010 / Accepted: 26 January 2011 / Published online: 18 February 2011 Ó Springer-Verlag 2011

Abstract We aimed to establish a method for evaluating malignant potential of prostate cancer using prostatic core needle biopsy (PCNB) before prostatectomy. If we can know the final pathological stage before treatment, we can select the most suitable therapeutic tactics. We then examined the expression of E-cadherin and type IV collagenase (MMP-9/-2), which play essential role in cancer cell invasion and metastasis. The expression ratio of MMP-9/-2 to E-cadherin (MER) is revealed as the relevant marker correlated with the final pathological stage and Gleason score by prostatectomy specimens. We next confirmed the significance of MER in PCNB, which means PCNB MER enables the prediction of the final pathologic stage at the cancer diagnosis. However, the methodology measuring MER is complicated to produce an observer-to-observer deviation. We then establish a bicolor fluorescent ISH (bicolor FISH) with a computerized fluorescence detector-based system. By this method, we can reduce an observer-to-observer deviation and a slide-to-slide deviation. The bicolor FISH-based MER is a useful tool for the preoperative evaluation of the final pathologic stage, by which we can assure a decision of prostatectomy indication. Keywords Prostate cancer  E-cadherin  Matrix metalloproteinase  VEGF  Invasion  Metastasis

Y. Chihara  H. Kuniyasu (&) Department of Molecular Pathology, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara 634-8521, Japan e-mail: [email protected] K. Fujimoto  Y. Hirao Department of Urology, Nara Medical University, Kashihara, Japan

Introduction Prostate cancer is the most common cancer and the second leading cause of cancer death in men in the United States [1]. While prostate cancer has extreme variability in the clinical natural history [2], most death are due to metastatic disease refractory to therapy [3]. The strongest predictive factors for advanced disease are Gleason score and a serum prostate-specific antigen (PSA) [4, 5]. The Gleason grading system and Gleason score [6–9] on the biopsy specimens or prostatectomy specimens correlate with final pathologic stage and the prognosis of prostate cancer patients [4, 6, 10, 11]. However, the intermediate (5–7) Gleason score tumors, especially Gleason score 7 tumors, which are three-fourth of all prostatic cancer cases, are unpredictable in their clinical aggressiveness by histological grading alone [8]. PSA has been used as a specific biomarker for prostate cancer [12]. However, the level of serum PSA is strongly affected by tumor volume and tumor differentiation. Their value and the chronological change are often based on individual and hardly compared case to case. Moreover, its biological function actually has not been elucidated. In these situations, we elucidate that matr