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PTEN 表达可作为乳腺癌错配修复检测的补充生物标志物。

PTEN Expression as a Complementary Biomarker for Mismatch Repair Testing in Breast Cancer.

机构信息

Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.

School of Pathology, University of Milan, 20122 Milan, Italy.

出版信息

Int J Mol Sci. 2020 Feb 21;21(4):1461. doi: 10.3390/ijms21041461.

DOI:10.3390/ijms21041461
PMID:32098071
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7073136/
Abstract

Mismatch repair (MMR) analysis in breast cancer may help to inform immunotherapy decisions but it lacks breast-specific guidelines. Unlike in other neoplasms, MMR protein loss shows intra-tumor heterogeneity and it is not mirrored by microsatellite instability in the breast. Additional biomarkers can improve MMR clinical testing. Phosphatase and tensin homolog (PTEN) inactivation is an early oncogenic event that is associated with MMR deficiency (dMMR) in several tumors. Here, we sought to characterize the diagnostic utility of PTEN expression analysis for MMR status assessment in breast cancer. A total of 608 breast cancers were profiled for their MMR and PTEN status. Proteins expression and distribution were analyzed by immunohistochemistry (IHC) on tissue microarrays and confirmed on full sections; PTEN copy number alterations were detected using a real-time PCR assay. Overall, 78 (12.8%) cases were MMR-heterogeneous (hMMR), while all patterns of PTEN expression showed no intra-tumor heterogeneity. Wild-type PTEN expression was observed in 15 (18.5%) dMMR tumors ( < 0.0001). Survival analyses revealed significant correlations between MMR-proficient (pMMR), PTEN expression, and a better outcome. The positive predictive value of PTEN-retained status for pMMR ranged from 94.6% in estrogen receptor (ER)+/HER2- tumors to 100% in HER2-amplified and ER-/HER2- cases. We propose a novel diagnostic algorithm where PTEN expression analysis can be employed to identify pMMR breast cancers.

摘要

错配修复（MMR）分析在乳腺癌中可能有助于指导免疫治疗决策，但目前缺乏针对乳腺癌的特异性指南。与其他肿瘤不同，MMR 蛋白缺失表现出肿瘤内异质性，并且与乳腺癌中的微卫星不稳定性不对应。其他生物标志物可以改善 MMR 临床检测。磷酸酶和张力蛋白同源物（PTEN）失活是一种早期致癌事件，与几种肿瘤中的 MMR 缺陷（dMMR）相关。在这里，我们试图描述 PTEN 表达分析在乳腺癌中用于评估 MMR 状态的诊断效用。共对 608 例乳腺癌进行了 MMR 和 PTEN 状态的分析。通过组织微阵列上的免疫组织化学（IHC）分析和全切片验证来分析蛋白质的表达和分布；使用实时 PCR 检测 PTEN 拷贝数改变。总体而言，78 例（12.8%）为 MMR 异质性（hMMR），而所有 PTEN 表达模式均无肿瘤内异质性。野生型 PTEN 表达见于 15 例（18.5%）dMMR 肿瘤（<0.0001）。生存分析显示 MMR 功能正常（pMMR）、PTEN 表达与预后较好之间存在显著相关性。保留 PTEN 状态对 pMMR 的阳性预测值在雌激素受体（ER）+/HER2-肿瘤中为 94.6%，在 HER2 扩增和 ER-/HER2-病例中为 100%。我们提出了一种新的诊断算法，其中可以使用 PTEN 表达分析来识别 pMMR 乳腺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55ae/7073136/2a576d9df6fc/ijms-21-01461-g005.jpg
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