Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr 52, 20246, Hamburg, Germany.
General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Mol Med. 2020 Mar 6;26(1):24. doi: 10.1186/s10020-020-00148-4.
TFAP2D is a transcription factor important for modulating gene expression in embryogenesis. Its expression and prognostic role in prostate cancer has not been evaluated.
Therefore, a tissue microarray containing 17,747 prostate cancer specimens with associated pathological, clinical, and molecular data was analyzed by immunohistochemistry to assess the role of TFAP2D.
TFAP2D expression was typically increased in prostate cancer as compared to adjacent non-neoplastic glands. TFAP2D staining was considered negative in 24.3% and positive in 75.7% of 13,545 interpretable cancers. TFAP2D staining was significantly linked to advanced tumor stage, high classical and quantitative Gleason grade, lymph node metastasis, and a positive surgical margin (p ≤ 0.0045). TFAP2D positivity was more common in ERG fusion positive (88.7%) than in ERG negative cancers (66.8%; p < 0.0001). Subset analyses in 3776 cancers with and 4722 cancers without TMPRSS2:ERG fusion revealed that associations with tumor phenotype and patient outcome were largely driven by the subset of ERG negative tumors. Multivariate analysis did not identify TFAP2D protein expression levels as a robust independent prognostic parameter. Positive TFAP2D immunostaining was significantly associated with 10 of 11 previously analyzed chromosomal deletions in ERG negative cancers (p ≤ 0.0244 each) indicating that elevated TFAP2D expression parallels genomic instability in prostate cancer.
These data demonstrate that TFAP2D protein overexpression is linked to prostate cancer progression and genomic instability in ERG negative prostate cancers.
TFAP2D 是一种转录因子，对于调节胚胎发生中的基因表达很重要。其在前列腺癌中的表达和预后作用尚未得到评估。
因此，通过免疫组织化学分析了包含 17747 例前列腺癌标本的组织微阵列，这些标本具有相关的病理、临床和分子数据，以评估 TFAP2D 的作用。
与相邻的非肿瘤腺相比，TFAP2D 在前列腺癌中的表达通常增加。在 13545 例可解释的癌症中，24.3%的 TFAP2D 染色被认为是阴性的，75.7%是阳性的。TFAP2D 染色与晚期肿瘤分期、高经典和定量 Gleason 分级、淋巴结转移和阳性手术切缘显著相关（p≤0.0045）。在 ERG 融合阳性（88.7%）中，TFAP2D 阳性比 ERG 阴性癌症（66.8%）更常见（p<0.0001）。在有和没有 TMPRSS2:ERG 融合的 3776 例癌症和 4722 例癌症的亚组分析中，与肿瘤表型和患者预后的关联主要由 ERG 阴性肿瘤亚组驱动。多变量分析并未确定 TFAP2D 蛋白表达水平是一个稳健的独立预后参数。阳性 TFAP2D 免疫染色与 ERG 阴性癌症中 11 个先前分析的染色体缺失中的 10 个显著相关（p≤0.0244 每个），表明升高的 TFAP2D 表达与前列腺癌中的基因组不稳定性平行。
这些数据表明，TFAP2D 蛋白过表达与 ERG 阴性前列腺癌的前列腺癌进展和基因组不稳定性有关。
