Clinical validity of proliferating cell nuclear antigen as an objective marker for evaluating biologic features in patients with untreated prostate cancer

Abstract

Background : Although Gleason grading may be the most useful system for evaluating biological activity of untreated prostate cancer, lack of interobserver validity with Gleason scores (GS) is an unsolved issue. In this study, the proliferating cell nuclear antigen labeling index (PCNA LI) in untreated prostate cancer was investigated in order to clarify the usefulness of supplemental and objective markers for evaluating the biologic features of prostate cancer. Methods : Sixty cases of prostate cancer were randomly selected from the cancer registry in Gunma University Hospital for this study. PCNA LI were evaluated using paraffin-embedded biopsy cores taken at diagnosis. Correlation of PCNA LI with the Gleason grading system, clinical stage, serum prostate-specific antigen (PSA) levels and age were evaluated. Cumulative rates of freedom from cause-specific death were also evaluated stratified by various clinicopathologic features, including PCNA LI using Kaplan-Meier analysis. Results : Proliferating cell nuclear antigen labeling index was significantly higher in patients with PSA levels over 100 ng/mL, advanced clinical stage ( > T4, N1 or M1 disease), higher Gleason grade or with a higher GS than in those with other clinicopathologic features. The 5-year cumulative rate of death from prostate cancer was significantly higher at 62% in patients with a PCNA LI of 20 or more than those with PCNA LI of less than 20, who accounted for 4%. Conclusions : Proliferating cell nuclear antigen labeling index in combination with Gleason grading system may be of clinical value in evaluating biologic features and also in predicting cause specific survival of prostate cancer in an objective, reliable and reproducible manner.

Small-Molecule Targeting of Proliferating Cell Nuclear Antigen Chromatin Association Inhibits Tumor Cell Growth

“…Tumor cells, regardless of their origins, express higher levels of PCNA (Celis and Olsen, 1994;Kallakury et al, 1999;Kimos et al, 2004;Malkas et al, 2006;Miyamoto et al, 2006;Naryzhny and Lee, 2007;Eltz et al, 2008;Naryzhny, 2008;Stuart-Harris et al, 2008;Zhong et al, 2008;Stoimenov and Helleday, 2009). Expression levels of PCNA correlate positively with other pathological indices in prostate cancer (Mulligan et al, 1997) and can serve as an independent prognosis marker (Miyamoto et al, 2006). Overexpression of PCNA is also a reliable biomarker for other tumor types (Kimos et al, 2004;Cappello et al, 2006;Stuart-Harris et al, 2008).…”

Antitumor Effects of a Novel Small Molecule Targeting PCNA Chromatin Association in Prostate Cancer

“…Tumor cells, regardless of their origin, express high levels of PCNA, presumably to accommodate their high degree of uncontrolled replication (21). For these reasons, PCNA is a reliable diagnostic and prognostic biomarker (21)(22)(23)(24)(25)(26)(27)(28).…”

Caracterização da próstata canina quanto a aspectos envolvidos na evolução para o carcinoma prostático

“…Foi demonstrado, por imunoistoquímica e quantificação por PCR, que a expressão de PCNA é maior em linhagens celulares de câncer de próstata em relação à de linhagem celular epitelial de próstata normal, e maior em CP em relação à de HPB e próstata normal (ZHONG et al, 2008). Miyamoto et al (2006), estudando 60 casos de CP, mostrou que o índice proliferativo estava aumentado em pacientes em estágio clínico avançado, alto grau de Gleason e valores de PSA > 100ng/mL. Já Helpap (1995) mostrou que o índice proliferativo é maior em PIN em relação ao epitélio benigno.…”

“…Sabe-se que distúrbios de proliferação e apoptose são eventos importantes nos estágios iniciais da carcinogênese, podendo ser úteis na caracterização de tecidos histologicamente normais, porém sob maior risco de sofrer transformação neoplásica. O indice proliferativo de células tumorais é sugerido como um parâmetro prognóstico adicional (MIYAMOTO et al, 2006).…”