PTEN loss and chromosome 8 alterations in Gleason grade 3 prostate cancer cores predicts the presence of un-sampled grade 4 tumor: implications for active surveillance

Bruce J. Trock, Helen Fedor, Bora Gurel, Robert Brian Jenkins, B. S. Knudsen, Samson W. Fine, Jonathan W. Said, H. Ballentine Carter, Tamara L. Lotan, Angelo M. de Marzo

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Men who enter active surveillance because their biopsy exhibits only Gleason grade 3 (G3) frequently have higher grade tumor missed by biopsy. Thus, biomarkers are needed that, when measured on G3 tissue, can predict the presence of higher grade tumor in the whole prostate. We evaluated whether PTEN loss, chromosome 8q gain (MYC) and/or 8p loss (LPL) measured only on G3 cores is associated with un-sampled G4 tumor. A tissue microarray was constructed of prostatectomy tissue from patients whose prostates exhibited only Gleason score 3+3, only 3+4 or only 4+3 tumor (n=50 per group). Cores sampled only from areas of G3 were evaluated for PTEN loss by immunohistochemistry, and PTEN deletion, LPL/8p loss and MYC/8q gain by fluorescence in situ hybridization. Biomarker results were compared between Gleason score 6 vs 7 tumors using conditional logistic regression. PTEN protein loss, odds ratio=4.99, P=0.033; MYC/8q gain, odds ratio=5.36, P=0.010; and LPL/8p loss, odds ratio=3.96, P=0.003 were significantly more common in G3 cores derived from Gleason 7 vs Gleason 6 tumors. PTEN gene deletion was not statistically significant. Associations were stronger comparing Gleason 4+3 vs 6 than for Gleason 3+4 vs 6. MYC/8q gain, LPL/8p loss and PTEN protein loss measured in G3 tissue microarray cores strongly differentiate whether the core comes from a Gleason 6 or Gleason 7 tumor. If validated to predict upgrading from G3 biopsy to prostatectomy these biomarkers could reduce the likelihood of enrolling high-risk men and facilitate safe patient selection for active surveillance.Modern Pathology advance online publication, 15 April 2016; doi:10.1038/modpathol.2016.63.

Original languageEnglish (US)
JournalModern Pathology
DOIs
StateAccepted/In press - Apr 15 2016

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Chromosomes, Human, Pair 8
Prostatic Neoplasms
Neoplasms
PTEN Phosphohydrolase
Neoplasm Grading
Biomarkers
Odds Ratio
Prostatectomy
Biopsy
Prostate
Gene Deletion
Fluorescence In Situ Hybridization
Patient Selection
Publications
Chromosomes
Logistic Models
Immunohistochemistry
Pathology

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

PTEN loss and chromosome 8 alterations in Gleason grade 3 prostate cancer cores predicts the presence of un-sampled grade 4 tumor : implications for active surveillance. / Trock, Bruce J.; Fedor, Helen; Gurel, Bora; Jenkins, Robert Brian; Knudsen, B. S.; Fine, Samson W.; Said, Jonathan W.; Carter, H. Ballentine; Lotan, Tamara L.; de Marzo, Angelo M.

In: Modern Pathology, 15.04.2016.

Research output: Contribution to journalArticle

Trock, Bruce J. ; Fedor, Helen ; Gurel, Bora ; Jenkins, Robert Brian ; Knudsen, B. S. ; Fine, Samson W. ; Said, Jonathan W. ; Carter, H. Ballentine ; Lotan, Tamara L. ; de Marzo, Angelo M. / PTEN loss and chromosome 8 alterations in Gleason grade 3 prostate cancer cores predicts the presence of un-sampled grade 4 tumor : implications for active surveillance. In: Modern Pathology. 2016.
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abstract = "Men who enter active surveillance because their biopsy exhibits only Gleason grade 3 (G3) frequently have higher grade tumor missed by biopsy. Thus, biomarkers are needed that, when measured on G3 tissue, can predict the presence of higher grade tumor in the whole prostate. We evaluated whether PTEN loss, chromosome 8q gain (MYC) and/or 8p loss (LPL) measured only on G3 cores is associated with un-sampled G4 tumor. A tissue microarray was constructed of prostatectomy tissue from patients whose prostates exhibited only Gleason score 3+3, only 3+4 or only 4+3 tumor (n=50 per group). Cores sampled only from areas of G3 were evaluated for PTEN loss by immunohistochemistry, and PTEN deletion, LPL/8p loss and MYC/8q gain by fluorescence in situ hybridization. Biomarker results were compared between Gleason score 6 vs 7 tumors using conditional logistic regression. PTEN protein loss, odds ratio=4.99, P=0.033; MYC/8q gain, odds ratio=5.36, P=0.010; and LPL/8p loss, odds ratio=3.96, P=0.003 were significantly more common in G3 cores derived from Gleason 7 vs Gleason 6 tumors. PTEN gene deletion was not statistically significant. Associations were stronger comparing Gleason 4+3 vs 6 than for Gleason 3+4 vs 6. MYC/8q gain, LPL/8p loss and PTEN protein loss measured in G3 tissue microarray cores strongly differentiate whether the core comes from a Gleason 6 or Gleason 7 tumor. If validated to predict upgrading from G3 biopsy to prostatectomy these biomarkers could reduce the likelihood of enrolling high-risk men and facilitate safe patient selection for active surveillance.Modern Pathology advance online publication, 15 April 2016; doi:10.1038/modpathol.2016.63.",
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