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- Title
Loss of the adhesion molecule CEACAM1 is associated with early biochemical recurrence in TMPRSS2:ERG fusion‐positive prostate cancers.
- Authors
Luebke, Andreas M.; Ricken, Wiebke; Kluth, Martina; Hube‐Magg, Claudia; Schroeder, Cornelia; Büscheck, Franziska; Möller, Katharina; Dum, David; Höflmayer, Doris; Weidemann, Sören; Fraune, Christoph; Hinsch, Andrea; Wittmer, Corinna; Schlomm, Thorsten; Huland, Hartwig; Heinzer, Hans; Graefen, Markus; Haese, Alexander; Minner, Sarah; Simon, Ronald
- Abstract
Altered expression of the carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) has been linked to adverse tumor features in various cancer types. To better understand the role of CEACAM1 in prostate cancer, we analyzed a tissue microarray containing tumor spots from 17,747 prostate cancer patients by means of immunohistochemistry. Normal prostate glands showed intense membranous CEACAM1 positivity. Immunostaining was interpretable in 13,625 cancers and was considered high in 28%, low in 43% and absent in 29% of tumors. Low and lost CEACAM1 expression was strongly linked to adverse tumor features including high classical and quantitative Gleason grade, lymph node metastasis, advanced tumor stage, positive surgical margin, a high number of genomic deletions and early biochemical recurrence (p < 0.0001 each). Subset analysis of molecularly defined cancer subsets revealed that these associations were strongest in V‐ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion‐positive cancers and that CEACAM1 loss was prognostic even in tumors harboring genomic deletions of the phosphatase and tensin homolog tumor suppressor (p < 0.0001). Multivariate analysis suggested that CEACAM1 analysis can provide independent prognostic information beyond established prognosis parameters at the stage of the initial biopsy when therapy decisions must be taken. In conclusion, loss of CEACAM1 expression predicts poor prognosis in prostate cancer and might provide clinically useful prognostic information particularly in cancers harboring the TMPRSS2:ERG fusion. What's new? Altered expression of the CEACAM1 adhesion molecule has been linked to adverse tumor features in various cancer types. The role of CEACAM1 in prostate cancer is poorly understood, however. Studying a large set of more than 13,000 cancers, here the authors found that loss of CEACAM1 expression was strongly linked to high Gleason grade, lymph node metastasis, advanced tumor stage, positive surgical margin, frequent genomic deletions, and early biochemical recurrence, especially in ERG‐fusion positive cancers. Furthermore, loss of CEACAM1 expression characterized a subset of tumors with a particularly poor prognosis, independently from established histo‐morphological features, with potential clinical applications.
- Subjects
PROSTATE cancer; PTEN protein; CELL adhesion molecules; PROSTATE cancer prognosis; CANCER relapse; PROSTATE cancer patients
- Publication
International Journal of Cancer, 2020, Vol 147, Issue 2, p575
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.32957