General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany.
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany.
BMC Cancer. 2019 Mar 1;19(1):193. doi: 10.1186/s12885-019-5390-1.
Microtubule-associated protein Tau (MAPT) overexpression has been linked to poor prognosis and decreased response to taxane-based therapies in several cancer types, but its relevance in prostate cancer is unknown.
In this study, MAPT expression was analyzed by immunohistochemistry on a tissue microarray containing 17,747 prostate cancers.
MAPT was absent in normal prostate epithelial cells but detectable in 1004 (8.2%) of 12,313 interpretable cancers. Its expression was associated with advanced tumor stage, high Gleason grade, positive lymph nodes, and early biochemical recurrence (p < 0.0001 each). For example, MAPT was found in 3.6% of 2072 Gleason ≤3 + 3 cancers but in 14.4% of 704 Gleason ≥4 + 4 cancers. High-level MAPT staining was also linked to TMPRSS2:ERG fusions (p < 0.0001). MAPT staining was seen in 15.2 and 16% of cancers with TMPRSS2:ERG fusion detected by immunohistochemistry and fluorescence in-situ hybridization, but in only 3.5 and 3.9% of cancers without ERG staining or ERG rearrangements. Moreover, an association was found between MAPT expression and PTEN deletions, with 19% MAPT positivity in 948 PTEN deleted cancers but only 7% MAPT positivity in 3895 tumors with normal PTEN copy numbers (p < 0.0001). Multivariate analysis revealed that the prognostic value of MAPT was independent from established parameters. Conventional large section analyses showed intratumoral MAPT heterogeneity in all three analyzed cancers.
The results of our study identify MAPT, as a moderate prognostic marker in prostate cancer, whose clinical impact, however, may be limited due to the rarity and heterogeneity of its expression.
微管相关蛋白 Tau（MAPT）过表达与几种癌症类型中的不良预后和对紫杉烷类药物治疗反应降低有关，但在前列腺癌中的相关性尚不清楚。
本研究通过包含 17747 例前列腺癌的组织微阵列进行免疫组织化学分析 MAPT 表达。
MAPT 在正常前列腺上皮细胞中不存在，但在 12313 例可解释的癌症中有 1004 例（8.2%）可检测到。其表达与肿瘤晚期、高 Gleason 分级、阳性淋巴结和早期生化复发相关（均 p<0.0001）。例如，在 2072 例 Gleason≤3+3 的癌症中，MAPT 存在于 3.6%的病例中，而在 704 例 Gleason≥4+4 的癌症中，MAPT 存在于 14.4%的病例中。高水平 MAPT 染色也与 TMPRSS2:ERG 融合相关（p<0.0001）。在免疫组化和荧光原位杂交检测到 TMPRSS2:ERG 融合的癌症中，MAPT 染色分别见于 15.2%和 16%的癌症，但在 ERG 染色或 ERG 重排阴性的癌症中仅见于 3.5%和 3.9%的癌症。此外，MAPT 表达与 PTEN 缺失之间存在关联，在 948 例 PTEN 缺失的癌症中有 19%的 MAPT 阳性，而在 3895 例 PTEN 拷贝数正常的肿瘤中有 7%的 MAPT 阳性（p<0.0001）。多变量分析显示，MAPT 的预后价值独立于既定参数。常规大切片分析显示，在所有三种分析的癌症中均存在肿瘤内 MAPT 异质性。
本研究结果将 MAPT 确定为前列腺癌中的中等预后标志物，但由于其表达的罕见性和异质性，其临床影响可能受到限制。
