NQO1 expression in pancreatic cancer and its potential use as a biomarker
NQO1 expression in pancreatic cancer and its potential use as a biomarker
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DOI：
10.1097/pai.0b013e31802e91d0
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发表时间：
2008-01-01
影响因子：
1.6
通讯作者：
Shroyer, Kenneth R.
中科院分区：
文献类型：
--
作者：
Awadallah, Nida S.;Dehn, Donna;Shroyer, Kenneth R.
胰腺导管腺癌（PDA）由于在诊断时已发生区域/转移性扩散，很少能被治愈。分子标志物的识别可能会提高PDA的诊断和早期检测水平。2 - 电子还原酶，NAD（P）H：醌氧化还原酶（NQO1）已被发现在包括PDA在内的许多实体肿瘤中过度表达，并且可能是一种有用的与临床相关的恶性肿瘤诊断标志物。在本研究中，我们使用了37例手术切除病例：24例PDA和13例良性胰腺组织标本。另外还包括16例来自胰腺内镜超声引导下细针穿刺（EUS - FNA）的标本作为试点系列。通过基于亲和素 - 生物素的免疫组织化学和免疫细胞化学方法检测NQO1。对NQO1阳性肿瘤细胞的染色强度和比例进行评分。在24例手术切除的PDA中的22例（92%）、9例恶性诊断的EUS - FNA中的9例（100%）、1例细胞学非典型但未诊断为恶性的EUS - FNA以及6例最初诊断为恶性阴性的EUS - FNA中的1例（17%）中检测到中等至强（NQO1染色为2 - 3级）。随后的组织学评估证实了所有9例细胞学阳性的EUS - FNA以及非典型病例中的恶性情况。最初诊断为恶性阴性的NQO1阳性病例在随后的组织活检中未显示出癌症的证据。在一些良性导管/细胞中也观察到了NQO1染色；然而，NQO1表达与细胞形态评估的相关性将假阳性诊断的风险降至最低。NQO1在PDA中一直过度表达。尽管在一些良性组织成分中也观察到NQO1，但该标志物可能是检测PDA的一种临床上有用的辅助诊断手段，与肿瘤分级/分期无关。
Pancreatic ductal adenocarcinoma (PDA) is rarely curable due to regional/metastatic spread at diagnosis. Identification of molecular markers may enhance diagnosis and early detection of PDA. The 2-electron reductase. NAD(P)H:quinone oxidoreductase (NQO1) has been found to be overexpressed in many solid tumors including PDA, and may be a useful clinically relevant diagnostic marker of malignancy. For this study. we used 37 surgical resection cases: 24 PDAs and 13 benign pancreatic tissue specimens. An additional 16 specimens from pancreatic endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) were included as a pilot series. NQO1 was detected by avidin-biotin based immunohistochemical and immunocytochemical methods. Both staining intensity and proportion of NQO1 positive tumor cells were scored. Moderate to strong (2 to 3 staining for NQO1 was detected in 22/24 (92%) surgically resected PDAs, 9/9 (100%) EUS-FNAs with malignant diagnoses, one cytologically atypical but not diagnostic for malignancy EUS-FNA, and 1/6 (17%) EUS-FNAs initially diagnosed as negative for malignancy. Subsequent histologic assessment confirmed malignancy in all 9 cytologically positive EUS-FNAs and in the atypical case. The NQO1 positive case initially diagnosed as negative for malignancy showed no evidence of carcinoma on subsequent tissue biopsy. NQO1 staining was also observed in some benign ducts/cells; however. correlation of NQO1 expression with cellular morphology assessment minimizes the risk of false positive diagnosis. NQO1 is consistently overexpressed in PDA. Although NQO1 is observed in some benign tissue components, this marker may be a clinically useful diagnostic adjunct for detection of PDA, independent of tumor grade/stage.