Tsourlakis Maria Christina, Eleftheriadou Agapi, Stender Annegret, Weigand Philipp, Grupp Katharina, Hube-Magg Claudia, Kluth Martina, Schroeder Cornelia, Steurer Stefan, Hinsch Andrea, Luebke Andreas, Angerer Alexander, Wittmer Corinna, Friedrich Emily, Göbel Cosima, Büscheck Franziska, Heinzer Hans, Graefen Markus, Simon Ronald, Sauter Guido, Wilczak Waldemar, Minner Sarah, Schlomm Thorsten, Jacobsen Frank
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Germany.
Carcinogenesis. 2017 Dec 7;38(12):1180-1187. doi: 10.1093/carcin/bgx105.
FOXA1 (Fork-head box protein A1, HNF-3a) is a transcription factor involved in androgen signaling with relevance for lineage-specific gene expression of the prostate. The expression was analyzed by immunohistochemistry on a tissue microarray containing 11152 prostate cancer specimens. Results were compared with tumor phenotype, biochemical recurrence, androgen receptor expression, ETS-related gene (ERG) status and other recurrent genomic alterations. FOXA1 expression was detectable in 97.6% of 8227 interpretable cancers and considered strong in 28.5%, moderate in 46.2% and weak in 22.9% of cases. High FOXA1 expression was associated with TMPRSS2:ERG rearrangement and ERG expression (P < 0.0001). High FOXA1 expression was linked to high Gleason grade, advanced pathological tumor (pT) stage and early PSA recurrence in ERG negative cancers (P < 0.0001), while these associations were either weak or absent in ERG positive cancers. In ERG negative cancers, the prognostic role of FOXA1 expression was independent of Gleason grade, pathological tumor stage, lymph node stage, surgical margin status and preoperative PSA. Independent prognostic value became even more evident if the analysis was limited to preoperatively available features such as biopsy Gleason grade, preoperative PSA, cT stage and FOXA1 expression (P < 0.0001). Within ERG negative cancers, FOXA1 expression was also strongly associated with PTEN and 5q21 deletions (P < 0.0001). High expression of FOXA1 is an independent prognostic parameter in ERG negative prostate cancer. Thus, FOXA1 measurement might provide clinically useful information in prostate cancer.
叉头框蛋白A1（FOXA1，肝细胞核因子3α）是一种参与雄激素信号传导的转录因子，与前列腺的谱系特异性基因表达相关。通过免疫组织化学方法对包含11152例前列腺癌标本的组织芯片进行了表达分析。将结果与肿瘤表型、生化复发、雄激素受体表达、ETS相关基因（ERG）状态及其他常见基因组改变进行了比较。在8227例可解释的癌症中，97.6%可检测到FOXA1表达，其中28.5%的病例为强表达，46.2%为中度表达，22.9%为弱表达。FOXA1高表达与TMPRSS2:ERG重排及ERG表达相关（P<0.0001）。在ERG阴性癌症中，FOXA1高表达与高Gleason分级、高级别病理肿瘤（pT）分期及早期前列腺特异抗原（PSA）复发相关（P<0.0001），而在ERG阳性癌症中，这些关联要么较弱要么不存在。在ERG阴性癌症中，FOXA1表达的预后作用独立于Gleason分级、病理肿瘤分期、淋巴结分期、手术切缘状态及术前PSA。如果分析仅限于术前可用特征，如活检Gleason分级、术前PSA、cT分期及FOXA1表达，独立预后价值会更加明显（P<0.0001）。在ERG阴性癌症中，FOXA1表达也与PTEN及5q21缺失密切相关（P<0.0001）。FOXA1高表达是ERG阴性前列腺癌的独立预后参数。因此，检测FOXA1可能为前列腺癌提供临床有用信息。
