ALDH1-positive intratumoral stromal cells indicate differentiated epithelial-like phenotype and good prognosis in prostate cancer

Paulina Nastały , Martyna Filipska , Colm Morrissey , Elke Eltze , Axel Semjonow , Burkhard Brandt , Klaus Pantel , Natalia Bednarz-Knoll

Abstract

Aldehyde dehydrogenase 1 (ALDH1) characterizes tumor-initiating cells in solid tumors; however, little is known about its expression in intratumoral stromal cells. Herein, we aimed to dissect its potential dual relevance in prostate cancer (PCa). ALDH1 expression was evaluated immunohistochemically in tumor and stromal cells in primary PCa and metastases. It was correlated to clinico-pathologic parameters, patients’ outcome, and selected proteins (CK5/6, CK14, CK8/18, CK19, EpCAM, Ki-67, E-cadherin, N-cadherin, and vimentin). ALDH1 protein was detected in tumor and stromal cells in 16% and 67% of 348 primary PCa, respectively. Tumor cell ALDH1 expression was associated with advanced T stage (P = 0.009), higher Gleason score (P = 0.016), shorter time to biochemical recurrence (TBR P = 0.010) and CK14 expression (P = 0.023). Stromal cell ALDH1 expression correlated to lower T stage (P = 0.008) and Gleason score (P = 0.016), N0 stage (P = 0.017), and longer TBR (P = 0.017). It occurred to be an independent predictor of good prognosis in the subgroup of d'Amico high-risk patients (multivariate analysis, P = 0.050). ALDH1-positive stromal cells were found in tumors characterized frequently by CK8/18 (P = 0.033) or EpCAM expression (P < 0.001) and rarely by epithelial-mesenchymal transition defined as CK8/18(−)vimentin(+) phenotype (P = 0.003). ALDH1-positive tumor and stromal cells were detected in 33% and 41% of hormone naive lymph node metastases (n = 63), 52% and 24% of castration resistant bone metastases, as well as 89% and 28% of castration resistant visceral metastases (n = 21), respectively. We have determined that contrary to tumor cell ALDH1, the presence of stromal ALDH1 is associated with epithelial phenotype of primary PCa, improved clinical outcome, and is less frequent in PCa metastases.
Author Paulina Nastały
Paulina Nastały,,
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, Martyna Filipska (IFB)
Martyna Filipska,,
- Intercollegiate Faculty of Biotechnology UG
, Colm Morrissey
Colm Morrissey,,
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, Elke Eltze
Elke Eltze,,
-
, Axel Semjonow
Axel Semjonow,,
-
, Burkhard Brandt
Burkhard Brandt,,
-
, Klaus Pantel
Klaus Pantel,,
-
, Natalia Bednarz-Knoll (IFB)
Natalia Bednarz-Knoll,,
- Intercollegiate Faculty of Biotechnology UG
Journal seriesTranslational Research, ISSN 1931-5244, (A 40 pkt)
Issue year2019
Vol203
Pages49-56
Publication size in sheets0.5
ASJC Classification2704 Biochemistry, medical; 2739 Public Health, Environmental and Occupational Health; 2700 General Medicine
DOIDOI:10.1016/j.trsl.2018.08.007
URL https://doi.org/10.1016/j.trsl.2018.08.007
Languageen angielski
Score (nominal)40
ScoreMinisterial score = 40.0, 12-06-2019, ArticleFromJournal
Ministerial score (2013-2016) = 40.0, 12-06-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.213; WoS Impact Factor: 2017 = 4.88 (2) - 2017=4.496 (5)
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