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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

Correlation of IHC parameters HOXB13, androgen receptor (AR) and cytoplasmic PSA(A) strong HOXB13 expression and AR, (B) strong PSA expression and HOXB13, and (C) strong PSA expression and AR.
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Figure 4: Correlation of IHC parameters HOXB13, androgen receptor (AR) and cytoplasmic PSA(A) strong HOXB13 expression and AR, (B) strong PSA expression and HOXB13, and (C) strong PSA expression and AR.

Mentions: To search for associations between expression of HOXB13 and its co-regulator AR, we included data from a previous study [19]. There was a strong positive link between overexpression of HOXB13 and high-level AR expression (p < 0.0001, Figure 4A). Strong HOXB13 expression was found in 17% of cancers with strong AR expression, but only in 1.3% of AR-negative tumors. HOXB13 and AR expression were further compared to PSA immunohistochemical results because PSA was described to be down regulated by AR/HOXB13 [25]. As expected from these studies, HOXB13 was inversely linked to PSA (p < 0.0001, Figure 4B). Strong PSA expression was seen in 55.1% of HOXB13-negative tumors, but only in 33.1% of cancers with strong HOXB13 expression. Likewise, AR expression was inversely related to PSA levels. High-level PSA was found in 65.9% of AR-negative cancers, but only in 39% of strongly AR-positive tumors (p < 0.0001, Figure 4C).


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)

Correlation of IHC parameters HOXB13, androgen receptor (AR) and cytoplasmic PSA(A) strong HOXB13 expression and AR, (B) strong PSA expression and HOXB13, and (C) strong PSA expression and AR.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Correlation of IHC parameters HOXB13, androgen receptor (AR) and cytoplasmic PSA(A) strong HOXB13 expression and AR, (B) strong PSA expression and HOXB13, and (C) strong PSA expression and AR.
Mentions: To search for associations between expression of HOXB13 and its co-regulator AR, we included data from a previous study [19]. There was a strong positive link between overexpression of HOXB13 and high-level AR expression (p < 0.0001, Figure 4A). Strong HOXB13 expression was found in 17% of cancers with strong AR expression, but only in 1.3% of AR-negative tumors. HOXB13 and AR expression were further compared to PSA immunohistochemical results because PSA was described to be down regulated by AR/HOXB13 [25]. As expected from these studies, HOXB13 was inversely linked to PSA (p < 0.0001, Figure 4B). Strong PSA expression was seen in 55.1% of HOXB13-negative tumors, but only in 33.1% of cancers with strong HOXB13 expression. Likewise, AR expression was inversely related to PSA levels. High-level PSA was found in 65.9% of AR-negative cancers, but only in 39% of strongly AR-positive tumors (p < 0.0001, Figure 4C).

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