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Clinical Studies

Pentraxin 3: A Novel Biomarker for Predicting Progression from Prostatic Inflammation to Prostate Cancer

Giovanni Stallone, Luigi Cormio, Giuseppe Stefano Netti, Barbara Infante, Oscar Selvaggio, Giuseppe Di Fino, Elena Ranieri, Francesca Bruno, Clelia Prattichizzo, Francesca Sanguedolce, Simona Tortorella, Pantaleo Bufo, Giuseppe Grandaliano and Giuseppe Carrieri
Giovanni Stallone
1Nephrology Dialysis and Transplantation Unit, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Luigi Cormio
2Urology and Renal Transplantation Unit, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Giuseppe Stefano Netti
3Clinical Pathology Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Barbara Infante
1Nephrology Dialysis and Transplantation Unit, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Oscar Selvaggio
2Urology and Renal Transplantation Unit, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Giuseppe Di Fino
2Urology and Renal Transplantation Unit, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Elena Ranieri
3Clinical Pathology Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Francesca Bruno
1Nephrology Dialysis and Transplantation Unit, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Clelia Prattichizzo
1Nephrology Dialysis and Transplantation Unit, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Francesca Sanguedolce
4Pathology Unit, Department of Clinical and Experimental Medicine, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Simona Tortorella
4Pathology Unit, Department of Clinical and Experimental Medicine, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Pantaleo Bufo
4Pathology Unit, Department of Clinical and Experimental Medicine, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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Giuseppe Grandaliano
1Nephrology Dialysis and Transplantation Unit, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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  • For correspondence: giusepppe.grandaliano@unifg.it
Giuseppe Carrieri
2Urology and Renal Transplantation Unit, University of Foggia, Viale Luigi Pinto, Foggia, Italy.
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DOI: 10.1158/0008-5472.CAN-14-0369 Published August 2014
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    Figure 1.

    PTX3 protein expression in prostatic tissue (A–E). Indirect immunofluorescence for PTX3 showed limited staining in both first (A) and second (B) PBx samples of patients who did not develop prostate cancer (group B); conversely, PTX3 staining was moderate in the first (C) and diffuse in the second (D) PBx samples of patients who developed prostate cancer (group A). Quantification of specific PTX3 fluorescence demonstrated low PTX3 tissue levels in group B patients at both first and second PBx, as opposed to a higher PTX3 tissue levels at first PBx that further increased at second PBx in group A patients (E). Nuclei are highlighted with TO-PRO in blue. Results are representative of 10 patients. *, P = 0.02; **, P = 0.002; ***, P = 0.03.

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    Figure 2.

    Colocalization of PTX3 and PSA. A–H, double-label immunofluorescence showing expression of PTX3 (green; A and E) and PSA (red; B and F) in the prostate tissue of group A (A–D) and group B (E–H). TO-PRO-3 counterstains nuclei (blue; C and G). Merged images (yellow) demonstrate coexpression of PTX3 and PSA by resident prostate cells both in group A (D) and in group B (H), although PTX3 expression is limited in group B, as expected. Results are representative of 10 patients.

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    Figure 3.

    Colocalization of PTX3 with MPO, CD20, and CD3. A–H, double-label immunofluorescence showing expression of PTX3 (green; A and E) and MPO (red; B and F) in the prostate tissue of group A (A–D) and group B (E–H). TO-PRO-3 counterstains nuclei (blue; C and G). Merged images (yellow; D and H) demonstrate that numerous infiltrating neutrophils (MPO-positive cells, white arrows) express PTX3, but prostatic resident cells are the major source of this long pentraxin. I–P, double-label immunofluorescence showing expression of PTX3 (green; I and M) and CD20 (red; J and N) in the prostate tissue of group A (I–L) and group B (M–P). TO-PRO-3 counterstains nuclei (blue; K and O). Merged images (yellow; D and H) show very rare infiltrating B cells (CD20-positive cells, white arrow) expressing PTX3. Q–X, double-label immunofluorescence showing expression of PTX3 (green; Q and U) and CD3 (red; R and V) in the prostate tissue of group A (Q–T) and group B (U–X). TO-PRO-3 counterstains nuclei (blue; S and W). In merged images (yellow; T and X), some infiltrating T cells (CD3-positive cells, white arrows) express PTX3. Results are representative of 10 patients for experimental groups.

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    Figure 4.

    PTX3 (A), PSA (B), and CRP (C) serum levels. PTX serum levels were significantly higher in patients with prostatic cancer (n = 56) in comparison with patients with BPH (n = 61; 6.1 ± 4.9 vs. 2.4 ± 1.1 pg/mL; t test for unpaired data; P < 0.001; A). PSA and CRP serum levels were assessed in the same cohort of patients, but no differences were found in relation to histologic diagnosis (8.3 ± 4.4 vs. 7.5±3.7 ng/mL for PSA and 2.8 ± 2.2 vs. 2.4 ± 2.2 mg/dL for CRP in patients with prostatic cancer and BPH, respectively; P = nonsignificant (ns); B and C, respectively). Data are expressed as median and 25th and 75th percentiles in boxes and 5th and 95th percentiles as whiskers.

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    Figure 5.

    ROC for PXT3, PSA, and CRP serum levels. The ROC curve confirms the significant association of PTX3 serum levels with the histologic diagnosis of prostate carcinoma (AUC 0.922; P < 0.001) with a cutoff value of 3.25 ng/mL (specificity 88.5%; sensitivity 89.3%; A). Nonstatistically significant results were obtained for PSA (AUC 0.5569, P = 0.297; B) and CRP (AUC 0.536, P = 0.497; C).

Tables

  • Figures
  • Table 1.

    Clinical and histologic characteristics of the PBx study population

    Group A (n = 20)Group B (n = 20)P
    Baseline clinical and histologic variables
     Age, y68.3 ± 9.464.8 ± 9.20.2
     Suspicious DRE ( %)31.820.00.4
     Prostate volume (mL)50.4 ± 29.052.6 ± 16.90.7
     Total PSA levels (ng/mL)7.7 ± 2.78.2 ± 5.90.7
     PSA density (ng/mL*mL)0.2 ± 0.10.2 ± 0.30.9
     International Prostate Symptom Score (I-PSS)12.1 ± 10.315.8 ± 10.50.6
     Flow max (mL/s)13.0 ± 7.110.4 ± 4.40.1
     Post-void residual (mL)39.3 ± 29.941.0 ± 20.90.8
     Histologic grading of prostatic inflammation (G≥2)3/20 (15%)4/20 (20%)0.8
     Aggressiveness of prostatic inflammation (A≥2)2/20 (10%)3/20 (15%)0.8
    Clinical and histologic variables at second biopsy
     Prostate volume (mL)51.3 ± 27.854.1 ± 12.70.1
     Histologic grading of prostatic inflammation (G≥2)6/20 (30%)9/20 (45%)0.06
     Aggressiveness of prostatic inflammation (A≥2)5/20 (25%)7/20 (35%)0.40
    Biopsy Gleason score
     ≤613 (65%)
     75 (25%)
     ≥82 (10%)
  • Table 2.

    Clinical and histologic characteristics of the independent set of patients with PTX3 serum evaluation

    BPH (n = 61)Prostate cancer (n = 56)P
    Age, y61.5 ± 10.465.6 ± 6.60.2
    Suspicious DRE (%)29.537.50.4
    Prostate volume (mL)59.3 ± 20.955.9 ± 13.80.7
    Total PSA levels (ng/mL)7.5 ± 3.78.3 ± 4.40.7
    PSA density (ng/mL*mL)0.4 ± 0.10.7 ± 0.30.5
    International Prostate Symptom Score (I-PSS)10.8 ± 8.113.1 ± 9.60.6
    Flow max (mL/s)15.0 ± 9.311.7 ± 7.30.1
    Post-void residual (mL)42.3 ± 21.533.0 ± 18.70.7
    Histologic grading of prostatic inflammation (G≥2)15/61 (24.5%)18/56 (34.1%)0.6
    Aggressiveness of prostatic inflammation (A≥2)9/61 (14.7%)11/56 (19.6%)0.4
    Biopsy Gleason score
     ≤635 (62.5%)
     713 (23.2%)
     ≥88 (14.3%)
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Cancer Research: 74 (16)
August 2014
Volume 74, Issue 16
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Pentraxin 3: A Novel Biomarker for Predicting Progression from Prostatic Inflammation to Prostate Cancer
Giovanni Stallone, Luigi Cormio, Giuseppe Stefano Netti, Barbara Infante, Oscar Selvaggio, Giuseppe Di Fino, Elena Ranieri, Francesca Bruno, Clelia Prattichizzo, Francesca Sanguedolce, Simona Tortorella, Pantaleo Bufo, Giuseppe Grandaliano and Giuseppe Carrieri
Cancer Res August 15 2014 (74) (16) 4230-4238; DOI: 10.1158/0008-5472.CAN-14-0369

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Pentraxin 3: A Novel Biomarker for Predicting Progression from Prostatic Inflammation to Prostate Cancer
Giovanni Stallone, Luigi Cormio, Giuseppe Stefano Netti, Barbara Infante, Oscar Selvaggio, Giuseppe Di Fino, Elena Ranieri, Francesca Bruno, Clelia Prattichizzo, Francesca Sanguedolce, Simona Tortorella, Pantaleo Bufo, Giuseppe Grandaliano and Giuseppe Carrieri
Cancer Res August 15 2014 (74) (16) 4230-4238; DOI: 10.1158/0008-5472.CAN-14-0369
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