In depth evaluation of the prognostic and predictive utility of PTEN immunohistochemistry in colorectal carcinomas: performance of three antibodies with emphasis on intracellular and intratumoral heterogeneity.
In depth evaluation of the prognostic and predictive utility of PTEN immunohistochemistry in colorectal carcinomas: performance of three antibodies with emphasis on intracellular and intratumoral heterogeneity.
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DOI：
10.1186/s13000-016-0508-0
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发表时间：
2016-07-08
影响因子：
2.6
通讯作者：
Szász AM
中科院分区：
文献类型：
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作者：
Ágoston EI;Micsik T;Ács B;Fekete K;Hahn O;Baranyai Z;Dede K;Bodoky G;Bursics A;Kulka J;Krenács T;Győrffy B;Harsányi L;Szász AM
10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）功能丧失在晚期结直肠癌中经常被检测到。其检测被认为具有预后意义，并且被认为可预测对抗EGFR治疗的反应性。不幸的是，虽然免疫组化评估的PTEN表达是广泛的，它缺乏标准化和结果是很难在现有的出版物之间的可比性。将从55名患者中收集的、福尔马林固定和石蜡包埋的结直肠肿瘤组织样本组合成组织微阵列（TMA）块。我们使用三种不同的PTEN抗体来确定PTEN免疫组织化学标记的频率、强度和细胞内模式：Neomarkers、Dako和CellSignaling。我们通过使用三种评分方法（考虑染色频率和强度（H1-H3-评分））评估了结肠直肠癌选定区域及其淋巴结转移中的上述参数。我们还评估了细胞内定位。Dako和CellSignaling抗体主要染色细胞核，而Neomarkers抗体特异性染色细胞核。基于DAKO和CellSignaling抗体的染色，与正常结肠粘膜相比，所有肿瘤区域中的PTEN H评分显著较低。肿瘤内区域差异或匹配肿瘤和转移瘤之间的差异未用任何抗体检测到。Dako、CellSignaling和Neomarkers抗体均未显示PTEN表达与pT、Dukes/MAC和临床分期之间存在显著相关性。KRAS状态、组织学分级与基于用Neomarkers抗体染色的PTEN H评分相关。PTEN H评分与MMR状态无关。基于用任一抗体染色，PTEN H评分未显示与无复发存活的任何相关性。虽然根据两种抗体，结直肠癌中的PTEN表达降低，但三种应用的PTEN抗体均不能证明与临床病理数据的显著相关性，也没有预后价值。因此，我们可以得出结论，免疫组化PTEN研究仍然是一个挑战，需要更多的情况下，以澄清其作为一个预后和预测工具，在CRC更标准化的评估。免疫组化方法的标准化是评价过程中的关键，本文对此进行了进一步的探讨。本文的在线版本（doi：10.1186/s13000-016-0508-0）包含补充材料，可供授权用户使用。
Phosphatase and tensin homolog deleted in chromosome 10 (PTEN) loss of function is frequently detected in advanced colorectal cancer. Its detection is thought to have prognostic significance and it is being considered to predict responsiveness to anti-EGFR therapy. Unfortunately, while immunohistochemical assessment of PTEN expression is widespread, it lacks standardization and the results are hardly comparable across the available publications. Retrospectively collected, formalin-fixed and paraffin-embedded colorectal tumor tissue samples from 55 patients were combined into tissue microarray (TMA) blocks. We used three different PTEN antibodies to determine the frequency, intensity and intracellular pattern of PTEN immunohistochemical labeling: Neomarkers, Dako and CellSignaling. We evaluated the aforementioned parameters in selected regions of colorectal cancers and in their lymph node metastases by using three scoring methods that take into consideration both staining frequency and intensity (H1-H3-score). We also evaluated intracellular localization. The Dako and CellSignaling antibodies stained predominantly cytoplasms, while the Neomarkers antibody specifically stained cell nuclei. PTEN H-scores were significantly lower in all tumor areas as compared to the normal colonic mucosa based on staining with the DAKO and CellSignaling antibodies. Intratumoral regional differences or differences between matching tumors and metastases were not detected with any of the antibodies. Neither Dako, neither CellSignaling, nor the Neomarkers antibodies revealed a significant correlation between PTEN expression and pT, Dukes/MAC and clinical stage. KRAS status, histological grade correlated with PTEN H-scores based on staining with the Neomarkers antibody. PTEN H-scores did not correlate with MMR status. PTEN H-scores did not show any correlation with relapse-free survival based on staining with either antibody. While PTEN expression decreased in colorectal cancer according to two antibodies, neither of the three applied PTEN antibodies could justify significant correlation with clinicopathological data, nor had prognostic value. Thus, we might conclude that immunohistochemical PTEN investigation remains a challenge requiring more standardized evaluation on larger number of cases to clarify its utility as a prognostic and predictive tool in CRC. The standardization of immunohistochemical method is key in the evaluation process, which is further discussed. The online version of this article (doi:10.1186/s13000-016-0508-0) contains supplementary material, which is available to authorized users.