# Role of Cell‐Cycle Proliferation Test, Triple Hit Phenotype, and TMPRSS2‐ERG Expression to Evaluate the Risk of Progression in Prostate Cancer Patients Under Active Surveillance

**Authors:** Marco Oderda, Giulia Orlando, Giorgio Calleris, Giulia Capella, Luisa Delsedime, Eleonora Duregon, Paola Francia di Celle, Donatella Pacchioni, Ian Marc Bonapace, Zaibunnisa Zaibunnisa, Daniele D'Agate, Gabriele Montefusco, Claudia Filippini, Mauro Papotti, Paolo Gontero

PMC · DOI: 10.1002/pros.24921 · The Prostate · 2025-05-29

## TL;DR

This study evaluates biomarkers to predict prostate cancer progression in patients on active surveillance, finding that the Prolaris cell-cycle test is useful while others are not.

## Contribution

The study demonstrates that the CCP test is a significant predictor of progression risk in prostate cancer patients.

## Key findings

- The CCP test's molecular score was significantly associated with cancer progression (HR 8.5, p = 0.02).
- The triple hit phenotype and TMPRSS2-ERG expression were not significantly linked to progression.
- IHC analysis was only feasible in 17 patients due to limited biopsy material.

## Abstract

An accurate estimation of progression risk in patients with prostate cancer (PCa) amenable to active surveillance (AS) is still an unmet need. Among available biomarkers, we considered Prolaris cell‐cycle progression (CCP) test, “triple hit” phenotype (ERG overexpression, PTEN and prostein expression loss) and elevated expression levels of TMPRSS2‐ERG gene fusions.

We performed a case‐control study, enrolling patients that entered the AS programme at our tertiary referral Institution. Men subsequently undergoing radical prostatectomy for progression were considered as “cases”, while men still on AS at the end of the follow‐up period were labeled as “controls”. CCP test, triple hit and TMPRSS2‐ERG expression analyses were performed on tumoral tissue retrieved from biopsies at enrollment. Their ability to distinguish “cases” and “controls” was evaluated. According to power analysis, the study required 40 patients.

Patients had comparable baseline characteristics. CCP test suggested to continue AS in 75% of controls and to undergo an active treatment in 75% of cases. CCP molecular score (HR 8.5, p = 0.02) was significantly associated with progression in multivariable logistic regression. No significant differences were found in terms of “triple hit” or TMPRSS2:ERG expression. IHC analysis was feasible only in 17 patients due to insufficient material.

CCP test may be a useful tool to estimate the risk of progression in PCa patients and guide the decision between AS and active treatment. Triple hit phenotype or TMPRSS:ERG fusion status was not associated with progression.

## Linked entities

- **Genes:** ERG (ETS transcription factor ERG) [NCBI Gene 2078], PTEN (phosphatase and tensin homolog) [NCBI Gene 5728], SLC45A3 (solute carrier family 45 member 3) [NCBI Gene 102115659]
- **Diseases:** prostate cancer (MONDO:0005159)

## Full-text entities

- **Genes:** PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, TMPRSS2 (transmembrane serine protease 2) [NCBI Gene 7113] {aka PRSS10}, ERG (ETS transcription factor ERG) [NCBI Gene 2078] {aka LMPHM14, erg-3, p55}, GZMK (granzyme K) [NCBI Gene 3003] {aka GrK, TRYP2}
- **Diseases:** PCa (MESH:D011471)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

26 references — full list in the complete paper: https://tomesphere.com/paper/PMC12278703/full.md

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Source: https://tomesphere.com/paper/PMC12278703