The Queen Elizabeth Hospital, TQEH Woodville Road, Woodville South, SA 5011, Australia.
BMC Cancer. 2014 Feb 25;14:128. doi: 10.1186/1471-2407-14-128.
Loss of phosphatase and tensin homologue (PTEN) function evaluated by loss of PTEN protein expression on immunohistochemistry (IHC) has been reported as both prognostic in metastatic colorectal cancer and predictive of response to anti-EGFR monoclonal antibodies although results remain uncertain. Difficulties in the methodological assessment of PTEN are likely to be a major contributor to recent conflicting results.
We assessed loss of PTEN function in 51 colorectal cancer specimens using Taqman® copy number variation (CNV) and IHC. Two blinded pathologists performed independent IHC assessment on each specimen and inter-observer variability of IHC assessment and concordance of IHC versus Taqman® CNV was assessed.
Concordance between pathologists (PTEN loss vs no loss) on IHC assessment was 37/51 (73%). In specimens with concordant IHC assessment, concordance between IHC and Taqman® copy number in PTEN loss assessment was 25/37 (68%).
Assessment PTEN loss in colorectal cancer is limited by the inter-observer variability of IHC, and discordance of CNV with loss of protein expression. An understanding of the genetic mechanisms of PTEN loss and implementation of improved and standardized methodologies of PTEN assessment are required to clarify the role of PTEN as a biomarker in colorectal cancer.
免疫组织化学（IHC）检测到磷酸酶和张力蛋白同源物（PTEN）蛋白表达缺失，被认为与转移性结直肠癌的预后相关，并预测对抗 EGFR 单克隆抗体的反应，但结果仍不确定。PTEN 方法学评估的困难可能是导致最近结果相互矛盾的主要原因。
我们使用 Taqman®拷贝数变异（CNV）和 IHC 评估了 51 例结直肠癌标本中 PTEN 功能的缺失。两位盲法病理学家对每个标本进行独立的 IHC 评估，并评估了 IHC 评估的观察者间变异性和 IHC 与 Taqman®CNV 的一致性。
病理学家（PTEN 缺失与无缺失）在 IHC 评估上的一致性为 37/51（73%）。在具有一致 IHC 评估的标本中，在 PTEN 缺失评估中 IHC 与 Taqman®拷贝数的一致性为 25/37（68%）。
结直肠癌中 PTEN 缺失的评估受到 IHC 观察者间变异性的限制，并且与蛋白表达缺失的 CNV 不一致。需要了解 PTEN 缺失的遗传机制，并实施改进和标准化的 PTEN 评估方法，以阐明 PTEN 作为结直肠癌生物标志物的作用。
