The Expression of Tyrosin-Phosphatase SHP-1 Is a Novel Prognostic Marker in Prostate Cancer
JI Lopez, A Ferruelo, B Colas, P Lopez-Ruiz, JC Angulo. Hospital de Cruces-Osakidetza, Basque Country Univ, Barakaldo, Bizkaia, Spain; Hospital de Getafe, Getafe, Madrid, Spain; Alcal Univ, Alcal de Henares, Madrid, Spain
Background: Tyrosin phosphatase SHP-1 has been recently described in human and murine prostate, and also in established prostate cancer cells. We hypothesize that this tyrosin-phosphatase may act as a suppressor gene and evaluate the expression of SHP-1 in a clinical series of prostate cancers with adequate long-term follow-up.
Design: A series of 114 patients with prostate cancer of variable clinical stage (22 T1, 34 T2, 46 T3 and 12 T4) were retrospectively analyzed. Specimens were collected from radical prostatectomy and TUR samples. Clinicopathologic data were homogeneously evaluated. Immunohistochemistry was performed using SHP-1 commercial antibody. Total RNA was extracted after deparaffination of tumour tissue. Real time RT-PCR was performed using specific primers for SHP-1 and ribosomal 18S. The quatification value of SHP-1 mRNA was described as each value relative to 18S mRNA ((Ct method). Ki-67 index and the expression of neuroendocrine markers (chromogranin and synaptophysin) were also evaluated. Multivariate analysis regarding disease-specific mortality was performed to evaluate prediction of prognosis.
Results: A total of 55 patients (48%) revealed immunohistochemical expression of SHP-1, and this finding was not associated to T category, metastatic status or Gleason score. All patients were followed with emphasis on disease specific mortality (28% die of cancer during follow-up). Patients dying of other cause were censored. Mean follow-up was 68.06 months (range, 10-166). Multivariate analysis revealed metastatic disease at the time of diagnosis (p<0.0001), Ki-67 index (p<0.0001), absence of SHP-1 expression on IHQ (p=0.003) and high Gleason score (p=0.05) were independent predictors. Expression of SHP-1 on RT-PCR was 2.07 times higher in tumours staining positive for SHP-1 on IHQ and 4.7 times lower in hormone-resistant disease.
Conclusions: Loss of tyrosin-phosphatase SHP-1 expression is an independent variable of poor prognosis in prostate cancer. This finding is not associated to standard clinico-pathologic predictors. It is likely that this enzyme may act as the product of a suppressor gene, the role of which in prostate cancer needs further investigation.Supported by the grant ISCIII PI020964.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 120, Wednesday Afternoon