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可切除非小细胞肺癌:螺旋 CT 动态增强容积参数与肿瘤乏氧免疫组化标志物的相关性。

Operable non-small cell lung cancer: correlation of volumetric helical dynamic contrast-enhanced CT parameters with immunohistochemical markers of tumor hypoxia.

机构信息

Mount Vernon Cancer Centre, Northwood, England.

出版信息

Radiology. 2012 Aug;264(2):581-9. doi: 10.1148/radiol.12111505. Epub 2012 Jun 14.

DOI:10.1148/radiol.12111505
PMID:22700554
Abstract

PURPOSE

To assess the relationship between helical dynamic contrast material-enhanced (DCE) computed tomographic (CT) parameters and immunohistochemical markers of hypoxia in patients with operable non-small cell lung cancer (NSCLC).

MATERIALS AND METHODS

After institutional review board approval was obtained, 20 prospective patients who were suspected of having NSCLC underwent whole-tumor DCE CT with kinetic modeling (Patlak analysis) 24 hours before scheduled surgery. Flow-extraction product (in milliliters per 100 milliliters per minute) and blood volume (in milliliters per 100 milliliters) were derived. After surgery, matched whole-tumor sections were stained for exogenous and endogenous markers of hypoxia (pimonidazole infused intravenously 24 hours before surgery, immediately after DCE CT; glucose transporter protein). Correlation between DCE CT parameters and immunohistochemical markers was assessed by using the Spearman rank correlation. DCE CT parameters and immunohistochemical markers were also compared according to pathologic subtype, grade, stage, and nodal status by using the Mann-Whitney test. P values less than .05 indicated a statistically significant difference.

RESULT

Fourteen patients with confirmed primary NSCLC underwent resection. There were negative correlations between blood volume and pimonidazole staining (r = -0.48, P = .004), and between flow-extraction product and glucose transporter protein expression (r = -0.50, P = .002). Flow-extraction product was significantly higher in adenocarcinomas than in squamous cell tumors (17.73 vs 11.46; P = .043). Glucose transporter protein expression was significantly lower for adenocarcinomas than for squamous tumors (14.07 vs 33.03; P < .001) and in node negative than in node positive tumors (15.63 vs 23.85; P = .005).

CONCLUSION

Blood volume and flow-extraction product derived at DCE CT correlated negatively with pimonidazole and glucose transporter protein expression, indicating the potential of these CT parameters as imaging biomarkers of hypoxia.

摘要

目的

评估可手术非小细胞肺癌(NSCLC)患者螺旋动态对比增强(DCE)计算机断层扫描(CT)参数与缺氧免疫组织化学标志物之间的关系。

材料与方法

获得机构审查委员会批准后,20 名疑似患有 NSCLC 的前瞻性患者在预定手术前 24 小时接受全肿瘤 DCE CT 检查,并进行动力学建模(Patlak 分析)。得出流量提取产物(每 100 毫升每分钟毫升数)和血容量(每 100 毫升毫升数)。手术后,对全肿瘤切片进行外源性和内源性缺氧标志物(手术前 24 小时静脉注射吡莫硝唑,DCE CT 后即刻;葡萄糖转运蛋白)染色。使用 Spearman 秩相关评估 DCE CT 参数与免疫组织化学标志物之间的相关性。根据病理亚型、分级、分期和淋巴结状态,使用 Mann-Whitney 检验比较 DCE CT 参数和免疫组织化学标志物。P 值小于.05 表示具有统计学意义的差异。

结果

14 名经证实患有原发性 NSCLC 的患者接受了切除术。血容量与吡莫硝唑染色之间存在负相关(r = -0.48,P =.004),流量提取产物与葡萄糖转运蛋白表达之间存在负相关(r = -0.50,P =.002)。腺癌的流量提取产物明显高于鳞癌(17.73 比 11.46;P =.043)。腺癌的葡萄糖转运蛋白表达明显低于鳞癌(14.07 比 33.03;P <.001),且在淋巴结阴性肿瘤中低于淋巴结阳性肿瘤(15.63 比 23.85;P =.005)。

结论

DCE CT 获得的血容量和流量提取产物与吡莫硝唑和葡萄糖转运蛋白表达呈负相关,表明这些 CT 参数有作为缺氧的成像生物标志物的潜力。

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