Limits...
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 immunostaining results and the ERG-status determined by IHC and FISH analysisBA (break apart) indicates rearrangement of the ERG gene according to FISH analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4494977&req=5

Figure 2: Association between HOXB13 immunostaining results and the ERG-status determined by IHC and FISH analysisBA (break apart) indicates rearrangement of the ERG gene according to FISH analysis.

Mentions: To evaluate whether HOXB13 expression is associated with ERG status in prostate cancers, we used data from previous studies (expanded from [18, 19]). Data on TMPRSS2:ERG fusion status obtained by FISH were available from 5,677 and by immunohistochemistry from 8,459 tumors with evaluable HOXB13 immunostaining. Data on both ERG FISH and IHC were available from 5,468 cancers, and an identical result (ERG IHC positive and break by FISH or ERG IHC negative and missing break by FISH) was found in 5,231 of 5,468 (95.7%) cancers. HOXB13 immunostaining was strongly linked to presence of TMPRSS2:ERG rearrangements and ERG expression. HOXB13 expression was seen in 63.4% (ERG IHC) and 64.1% (ERG FISH) of ERG-positive cancers but in only 44.1% and 49.9% of cancers without ERG staining and ERG rearrangement, respectively (p < 0.0001 each; Figure 2). HOXB13 immunostaining was linked to advanced pathological tumor stage, high Gleason grade, and lymph node metastasis (p < 0.0001 each) in subsets of both ERG-negative (Supplementary Table 2) and ERG-positive cancers (Supplementary Table 3).


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 immunostaining results and the ERG-status determined by IHC and FISH analysisBA (break apart) indicates rearrangement of the ERG gene according to FISH analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Association between HOXB13 immunostaining results and the ERG-status determined by IHC and FISH analysisBA (break apart) indicates rearrangement of the ERG gene according to FISH analysis.
Mentions: To evaluate whether HOXB13 expression is associated with ERG status in prostate cancers, we used data from previous studies (expanded from [18, 19]). Data on TMPRSS2:ERG fusion status obtained by FISH were available from 5,677 and by immunohistochemistry from 8,459 tumors with evaluable HOXB13 immunostaining. Data on both ERG FISH and IHC were available from 5,468 cancers, and an identical result (ERG IHC positive and break by FISH or ERG IHC negative and missing break by FISH) was found in 5,231 of 5,468 (95.7%) cancers. HOXB13 immunostaining was strongly linked to presence of TMPRSS2:ERG rearrangements and ERG expression. HOXB13 expression was seen in 63.4% (ERG IHC) and 64.1% (ERG FISH) of ERG-positive cancers but in only 44.1% and 49.9% of cancers without ERG staining and ERG rearrangement, respectively (p < 0.0001 each; Figure 2). HOXB13 immunostaining was linked to advanced pathological tumor stage, high Gleason grade, and lymph node metastasis (p < 0.0001 each) in subsets of both ERG-negative (Supplementary Table 2) and ERG-positive cancers (Supplementary Table 3).

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