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HOXB13 overexpression is an independent predictor of early PSA recurrence in prostate cancer treated by radical prostatectomy.

Zabalza CV, Adam M, Burdelski C, Wilczak W, Wittmer C, Kraft S, Krech T, Steurer S, Koop C, Hube-Magg C, Graefen M, Heinzer H, Minner S, Simon R, Sauter G, Schlomm T, Tsourlakis MC - Oncotarget (2015)

Bottom Line: HOXB13 expression was linked to advanced pT stage, high Gleason grade, positive lymph node status (p < 0.0001 each), high pre-operative PSA levels (p = 0.01), TMPRSS2:ERG fusion, PTEN deletions, AR expression, cell proliferation, reduced PSA expression and early PSA recurrence (p < 0.0001 each).The prognostic value of HOXB13 was independent from established parameters including Gleason, stage, nodal stage and PSA.HOXB13 appears to be a promising candidate for clinical routine tests either alone or in combination with other markers, including AR and PSA.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.

ABSTRACT
HOXB13 is a prostate cancer susceptibility gene which shows a cancer predisposing (G84E) mutation in 0.1-0.6% of males. We analyzed the prognostic impact of HOXB13 expression by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancers. Results were compared to tumor phenotype, biochemical recurrence, androgen receptor (AR) and prostate specific antigen (PSA) as well as molecular subtypes defined by ERG status and genomic deletions of 3p, 5q, 6q, and PTEN. HOXB13 immunostaining was detectable in 51.7% of 10,216 interpretable cancers and considered strong in 9.6%, moderate in 19.7% and weak in 22.3% of cases. HOXB13 expression was linked to advanced pT stage, high Gleason grade, positive lymph node status (p < 0.0001 each), high pre-operative PSA levels (p = 0.01), TMPRSS2:ERG fusion, PTEN deletions, AR expression, cell proliferation, reduced PSA expression and early PSA recurrence (p < 0.0001 each). The prognostic value of HOXB13 was independent from established parameters including Gleason, stage, nodal stage and PSA. Co-expression analysis identified a subset of tumors with high HOXB13 and AR but low PSA expression that had a particularly poor prognosis. HOXB13 appears to be a promising candidate for clinical routine tests either alone or in combination with other markers, including AR and PSA.

No MeSH data available.


Related in: MedlinePlus

Association between HOXB13 expression and biochemical recurrence(A) all cancers, (B) ERG-IHC positive cancers, and (C) ERG-IHC negative cancers. Combined effect of HOXB13, AR and PSA in (D) all cancers, (E) ERG-IHC positive cancers, and (F) ERG-IHC negative cancers.
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Figure 5: Association between HOXB13 expression and biochemical recurrence(A) all cancers, (B) ERG-IHC positive cancers, and (C) ERG-IHC negative cancers. Combined effect of HOXB13, AR and PSA in (D) all cancers, (E) ERG-IHC positive cancers, and (F) ERG-IHC negative cancers.

Mentions: Follow-up data were available from 9,474 patients with interpretable HOXB13 immunostaining on the TMA. Increasing levels of HOXB13 were equally paralleled by decreasing PSA recurrence-free intervals if all cancers were jointly analyzed (p < 0.0001, Figure 5A), as in subsets of ERG-IHC-positive (p < 0.0001, Figure 5B) or ERG-IHC-negative cancers p < 0.0001, Figure 5C). Because of the strong associations between HOXB13, AR and PSA, we extended the analyses to tumor subgroups stratified according to the following criteria 1) cancers with strong PSA staining irrespective of the HOXB13 and AR results (group 1: PSA high), 2) cancers with low (negative to weak) HOXB13 expression or low (negative to moderate) AR expression but low (negative-moderate) PSA expression (group 2: HOXB13 or AR low), and cancers with high (moderate-strong) HOXB13 expression and high (strong) AR expression but low PSA expression (group 3: HOXB13 and AR high, PSA low). These analyses revealed marked prognostic differences: Tumors with high PSA had the best, and tumors with high HOXB13 and AR, but low PSA, had the worst prognosis, while an intermediate prognosis was found for tumors with low expression of at least one of HOXB13 or AR (p < 0.0001, Figure 5D). These differences held also true in subsets of ERG-positive (p < 0.0001, Figure 5E) and ERG-negative cancers (p < 0.0001, Figure 5F).


HOXB13 overexpression is an independent predictor of early PSA recurrence in prostate cancer treated by radical prostatectomy.

Zabalza CV, Adam M, Burdelski C, Wilczak W, Wittmer C, Kraft S, Krech T, Steurer S, Koop C, Hube-Magg C, Graefen M, Heinzer H, Minner S, Simon R, Sauter G, Schlomm T, Tsourlakis MC - Oncotarget (2015)

Association between HOXB13 expression and biochemical recurrence(A) all cancers, (B) ERG-IHC positive cancers, and (C) ERG-IHC negative cancers. Combined effect of HOXB13, AR and PSA in (D) all cancers, (E) ERG-IHC positive cancers, and (F) ERG-IHC negative cancers.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4494977&req=5

Figure 5: Association between HOXB13 expression and biochemical recurrence(A) all cancers, (B) ERG-IHC positive cancers, and (C) ERG-IHC negative cancers. Combined effect of HOXB13, AR and PSA in (D) all cancers, (E) ERG-IHC positive cancers, and (F) ERG-IHC negative cancers.
Mentions: Follow-up data were available from 9,474 patients with interpretable HOXB13 immunostaining on the TMA. Increasing levels of HOXB13 were equally paralleled by decreasing PSA recurrence-free intervals if all cancers were jointly analyzed (p < 0.0001, Figure 5A), as in subsets of ERG-IHC-positive (p < 0.0001, Figure 5B) or ERG-IHC-negative cancers p < 0.0001, Figure 5C). Because of the strong associations between HOXB13, AR and PSA, we extended the analyses to tumor subgroups stratified according to the following criteria 1) cancers with strong PSA staining irrespective of the HOXB13 and AR results (group 1: PSA high), 2) cancers with low (negative to weak) HOXB13 expression or low (negative to moderate) AR expression but low (negative-moderate) PSA expression (group 2: HOXB13 or AR low), and cancers with high (moderate-strong) HOXB13 expression and high (strong) AR expression but low PSA expression (group 3: HOXB13 and AR high, PSA low). These analyses revealed marked prognostic differences: Tumors with high PSA had the best, and tumors with high HOXB13 and AR, but low PSA, had the worst prognosis, while an intermediate prognosis was found for tumors with low expression of at least one of HOXB13 or AR (p < 0.0001, Figure 5D). These differences held also true in subsets of ERG-positive (p < 0.0001, Figure 5E) and ERG-negative cancers (p < 0.0001, Figure 5F).

Bottom Line: HOXB13 expression was linked to advanced pT stage, high Gleason grade, positive lymph node status (p < 0.0001 each), high pre-operative PSA levels (p = 0.01), TMPRSS2:ERG fusion, PTEN deletions, AR expression, cell proliferation, reduced PSA expression and early PSA recurrence (p < 0.0001 each).The prognostic value of HOXB13 was independent from established parameters including Gleason, stage, nodal stage and PSA.HOXB13 appears to be a promising candidate for clinical routine tests either alone or in combination with other markers, including AR and PSA.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.

ABSTRACT
HOXB13 is a prostate cancer susceptibility gene which shows a cancer predisposing (G84E) mutation in 0.1-0.6% of males. We analyzed the prognostic impact of HOXB13 expression by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancers. Results were compared to tumor phenotype, biochemical recurrence, androgen receptor (AR) and prostate specific antigen (PSA) as well as molecular subtypes defined by ERG status and genomic deletions of 3p, 5q, 6q, and PTEN. HOXB13 immunostaining was detectable in 51.7% of 10,216 interpretable cancers and considered strong in 9.6%, moderate in 19.7% and weak in 22.3% of cases. HOXB13 expression was linked to advanced pT stage, high Gleason grade, positive lymph node status (p < 0.0001 each), high pre-operative PSA levels (p = 0.01), TMPRSS2:ERG fusion, PTEN deletions, AR expression, cell proliferation, reduced PSA expression and early PSA recurrence (p < 0.0001 each). The prognostic value of HOXB13 was independent from established parameters including Gleason, stage, nodal stage and PSA. Co-expression analysis identified a subset of tumors with high HOXB13 and AR but low PSA expression that had a particularly poor prognosis. HOXB13 appears to be a promising candidate for clinical routine tests either alone or in combination with other markers, including AR and PSA.

No MeSH data available.


Related in: MedlinePlus