High nuclear karyopherin [alpha] 2 expression is a strong and independent predictor of biochemical recurrence in prostate cancer patients treated by radical prostatectomy

Increased levels of karyopherin α2 (KPNA2) expression have been described to be linked to poor prognosis in a variety of malignancies. This study was undertaken to evaluate the clinical impact of KPNA2 expression and its association with key genomic alterations in prostate cancers. A tissue microarr...

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Published in:Modern pathology 2014-01, Vol.27 (1), p.96
Main Authors: Grupp, Katharina, Habermann, Mareike, Sirma, Hüseyin, Simon, Ronald, Steurer, Stefan, Hube-magg, Claudia, Prien, Kristina, Burkhardt, Lia, Jedrzejewska, Karolina, Salomon, Georg, Heinzer, Hans, Wilczak, Waldemar, Kluth, Martina, Izbicki, Jakob R, Sauter, Guido, Minner, Sarah, Schlomm, Thorsten, Tsourlakis, Maria Christina
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Language:English
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Antigens
Medical research
Pathology
Prostate cancer
Thoracic surgery
Tumors
Urology
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container_title Modern pathology
container_volume 27
creator Grupp, Katharina
Habermann, Mareike
Sirma, Hüseyin
Simon, Ronald
Steurer, Stefan
Hube-magg, Claudia
Prien, Kristina
Burkhardt, Lia
Jedrzejewska, Karolina
Salomon, Georg
Heinzer, Hans
Wilczak, Waldemar
Kluth, Martina
Izbicki, Jakob R
Sauter, Guido
Minner, Sarah
Schlomm, Thorsten
Tsourlakis, Maria Christina
description Increased levels of karyopherin α2 (KPNA2) expression have been described to be linked to poor prognosis in a variety of malignancies. This study was undertaken to evaluate the clinical impact of KPNA2 expression and its association with key genomic alterations in prostate cancers. A tissue microarray containing samples from 11152 prostate cancers was analyzed for KPNA2 expression by immunohistochemistry. Results were compared with oncological follow-up data and genomic alterations such as TMPRSS2-ERG fusions and deletions of PTEN, 5q21, 6q15 or 3p13. KPNA2 expression was absent or weak in benign prostatic glands and was found to be in weak, moderate or strong intensities in 68.4% of 7964 interpretable prostate cancers. KPNA2 positivity was significantly linked to the presence of ERG rearrangement (P
doi_str_mv 10.1038/modpathol.2013.127
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This study was undertaken to evaluate the clinical impact of KPNA2 expression and its association with key genomic alterations in prostate cancers. A tissue microarray containing samples from 11152 prostate cancers was analyzed for KPNA2 expression by immunohistochemistry. Results were compared with oncological follow-up data and genomic alterations such as TMPRSS2-ERG fusions and deletions of PTEN, 5q21, 6q15 or 3p13. KPNA2 expression was absent or weak in benign prostatic glands and was found to be in weak, moderate or strong intensities in 68.4% of 7964 interpretable prostate cancers. KPNA2 positivity was significantly linked to the presence of ERG rearrangement (P&lt;0.0001). In ERG-negative and -positive prostate cancers, KPNA2 immunostaining was significantly associated with advanced pathological tumor stage (pT3b/pT4), high Gleason grade and early biochemical recurrence (P&lt;0.0001 each). Multivariate analysis including all established prognostic criteria available after surgery revealed that the prognostic role of KPNA2 (P=0.001) was independent of high Gleason grade, advanced pathological tumor stage, high preoperative prostate-specific antigen level and positive surgical margin status (P&lt;0.0001 each). The comparison of KPNA2 expression with deletions of PTEN, 5q21, 6q15 and 3p13 in ERG-positive and -negative cancers revealed a strong link to PTEN deletions in both subgroups (P&lt;0.0001). In conclusion, the strong independent prognostic impact of KPNA2 expression raises the possibility that measurement of KPNA2 expression alone or in combination with other molecular parameters might possibly result in clinically useful information. 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subjects Antigens
Medical research
Pathology
Prostate cancer
Thoracic surgery
Tumors
Urology
title High nuclear karyopherin [alpha] 2 expression is a strong and independent predictor of biochemical recurrence in prostate cancer patients treated by radical prostatectomy
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