Upregulation of the heterogeneous nuclear ribonucleoprotein hnRNPA1 is an independent predictor of early biochemical recurrence in TMPRSS2:ERG fusion-negative prostate cancers
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Upregulation of the heterogeneous nuclear ribonucleoprotein hnRNPA1 is an independent predictor of early biochemical recurrence in TMPRSS2:ERG fusion-negative prostate cancers. / Möller, Katharina; Wecker, Anna Lena; Höflmayer, Doris; Fraune, Christoph; Makrypidi-Fraune, Georgia; Hube-Magg, Claudia; Kluth, Martina; Steurer, Stefan; Clauditz, Till S; Wilczak, Waldemar; Simon, Ronald; Sauter, Guido; Huland, Hartwig; Heinzer, Hans; Haese, Alexander; Schlomm, Thorsten; Weidemann, Sören; Luebke, Andreas M; Minner, Sarah; Bernreuther, Christian; Bonk, Sarah; Marx, Andreas.
In: VIRCHOWS ARCH, Vol. 477, No. 5, 11.2020, p. 625-636.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Upregulation of the heterogeneous nuclear ribonucleoprotein hnRNPA1 is an independent predictor of early biochemical recurrence in TMPRSS2:ERG fusion-negative prostate cancers
AU - Möller, Katharina
AU - Wecker, Anna Lena
AU - Höflmayer, Doris
AU - Fraune, Christoph
AU - Makrypidi-Fraune, Georgia
AU - Hube-Magg, Claudia
AU - Kluth, Martina
AU - Steurer, Stefan
AU - Clauditz, Till S
AU - Wilczak, Waldemar
AU - Simon, Ronald
AU - Sauter, Guido
AU - Huland, Hartwig
AU - Heinzer, Hans
AU - Haese, Alexander
AU - Schlomm, Thorsten
AU - Weidemann, Sören
AU - Luebke, Andreas M
AU - Minner, Sarah
AU - Bernreuther, Christian
AU - Bonk, Sarah
AU - Marx, Andreas
PY - 2020/11
Y1 - 2020/11
N2 - Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is a ubiquitous RNA splicing factor that is overexpressed and prognostically relevant in various human cancer types. To study the impact of hnRNPA1 expression in prostate cancer, we analyzed a tissue microarray containing 17,747 clinical prostate cancer specimens by immunohistochemistry. hnRNPA1 was expressed in normal prostate glandular cells but often overexpressed in cancer cells. hnRNPA1 immunostaining was interpretable in 14,258 cancers and considered strong in 33.4%, moderate in 45.9%, weak in 15.3%, and negative in 5.4%. Moderate to strong hnRNPA1 immunostaining was strongly linked to adverse tumor features including high classical and quantitative Gleason score, lymph node metastasis, advanced tumor stage, positive surgical margin, and early biochemical recurrence (p < 0.0001 each). The prognostic impact of hnRNPA1 immunostaining was independent of established preoperatively or postoperatively available prognostic parameters (p < 0.0001). Subset analyses revealed that all these associations were strongly driven by the fraction of cancers lacking the TMPRSS2:ERG gene fusion. Comparison with other key molecular data that were earlier obtained on the same TMA showed that hnRNPA1 overexpression was linked to high levels of androgen receptor (AR) expression (p < 0.0001) as well as presence of 9 of 11 chromosomal deletions (p < 0.05 each). A strong association between hnRNPA1 upregulation and tumor cell proliferation that was independent from the Gleason score supports a role for tumor cell aggressiveness. In conclusion, hnRNPA1 overexpression is an independent predictor of poor prognosis in ERG-negative prostate cancer. hnRNPA1 measurement, either alone or in combination, might provide prognostic information in ERG-negative prostate cancer.
AB - Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is a ubiquitous RNA splicing factor that is overexpressed and prognostically relevant in various human cancer types. To study the impact of hnRNPA1 expression in prostate cancer, we analyzed a tissue microarray containing 17,747 clinical prostate cancer specimens by immunohistochemistry. hnRNPA1 was expressed in normal prostate glandular cells but often overexpressed in cancer cells. hnRNPA1 immunostaining was interpretable in 14,258 cancers and considered strong in 33.4%, moderate in 45.9%, weak in 15.3%, and negative in 5.4%. Moderate to strong hnRNPA1 immunostaining was strongly linked to adverse tumor features including high classical and quantitative Gleason score, lymph node metastasis, advanced tumor stage, positive surgical margin, and early biochemical recurrence (p < 0.0001 each). The prognostic impact of hnRNPA1 immunostaining was independent of established preoperatively or postoperatively available prognostic parameters (p < 0.0001). Subset analyses revealed that all these associations were strongly driven by the fraction of cancers lacking the TMPRSS2:ERG gene fusion. Comparison with other key molecular data that were earlier obtained on the same TMA showed that hnRNPA1 overexpression was linked to high levels of androgen receptor (AR) expression (p < 0.0001) as well as presence of 9 of 11 chromosomal deletions (p < 0.05 each). A strong association between hnRNPA1 upregulation and tumor cell proliferation that was independent from the Gleason score supports a role for tumor cell aggressiveness. In conclusion, hnRNPA1 overexpression is an independent predictor of poor prognosis in ERG-negative prostate cancer. hnRNPA1 measurement, either alone or in combination, might provide prognostic information in ERG-negative prostate cancer.
U2 - 10.1007/s00428-020-02834-4
DO - 10.1007/s00428-020-02834-4
M3 - SCORING: Journal article
C2 - 32417965
VL - 477
SP - 625
EP - 636
JO - VIRCHOWS ARCH
JF - VIRCHOWS ARCH
SN - 0945-6317
IS - 5
ER -