早期鼻咽癌的18F-FDG摄取与肿瘤组织葡萄糖易化扩散转运蛋白表达的关系

目的:探讨早期鼻咽癌的18F-FDG摄取与肿瘤组织葡萄糖易化扩散转运蛋白表达的关系。方法:对2005年3月至2006年8月收治的42例早期鼻咽癌患者进行正电子发射体层显像(PET)检查,测定肿瘤最大值和标准摄取值(SUVmax和SUVmean);应用标准链霉菌抗生物素蛋白-过氧化物酶亲和(SP)免疫组化法检测40例患者肿瘤组织葡萄糖易化扩散转运蛋白1(Glut-1)的表达。结果:42例早期鼻咽癌组织的SU-Vmax与SUVmean分别为9.45±1.87和6.04±1.09;40例鼻咽癌组织Glut-1阳性细胞率为45.18%;鼻咽癌组织FDG摄取(SUVmax)和Glut-1表达的细胞阳性率呈弱相关(r=0.369,P=0.019)。结论:早期鼻咽癌组织FDG摄取与Glut-1过度表达相关。     

鼻咽癌^18F-FDG PET/CT标准化摄取值与肿瘤组织葡萄糖转运蛋白-1及增殖细胞核抗原过度表达的关系

背景与目的:恶性肿瘤的显著特征就是葡萄糖代谢增加,鼻咽癌的葡萄糖代谢增加可能与葡萄糖转运蛋白-1(Glut-1)有关,也可能与鼻咽癌细胞的快速增殖有关.本研究探讨鼻咽癌组织18F-脱氧葡萄糖(18F-FDG)的摄取与肿瘤组织葡萄糖转运蛋白及增殖细胞核抗原表达的关系.方法:对2005年3月至2006年8月间本院收治的40例鼻咽癌患者进行正电子发射体层显像检查,测定肿瘤最大摄取值,应用标准链霉菌抗生物素蛋白-过氧化物酶亲和免疫组化SP法检测40例患者肿瘤组织葡萄糖转运蛋白-1和增殖细胞核抗原的表达.结果:40例鼻咽癌组织的最大标准化摄取值SUVmax.为9.45±1.87;40例鼻咽癌组织G1ut-1阳性细胞率为45.18%,PCNA染色阳性细胞率为36.18%;鼻咽癌组织18F-FDG摄取(SUVmax)和组织Glut-1表达的阳性程度相关(r=0.369,P=0.019),鼻咽癌组织18F-FDG摄取(SUVmax)和组织PCNA表达的阳性程度无相关(r=0.135,P=0.407).结论:鼻咽癌组织18F-FDG摄取与Glut-1过度表达相关,与PCNA表达无关.     

鼻咽癌HK-Ⅱ和VEGF表达与PET/CT 显像18F-FDG摄取的关系

 目的 探讨鼻咽癌的18F-FDG摄取与肿瘤组织己糖激酶-Ⅱ(hexokinase-Ⅱ, HK-Ⅱ)及血管内皮细胞生长因子（VEGF）表达的关系。方法 对2005年3月至2006年8月收治的40例鼻咽癌患者进行正电子发射体层显像（PET）检查,测定肿瘤最大和标准摄取值（SUVmax和SUVmean）;应用标准链霉菌抗生物素蛋白 过氧化物酶亲和（SP）免疫组织化学法检测40例患者肿瘤组织己糖激酶-Ⅱ 和血管内皮细胞生长因子（VEGF）的表达。结果 40例鼻咽癌组织的SUVmax与 SUVmean分别为（9.45±1.87）和（6.04±1.09）;40例鼻咽癌组织HK-Ⅱ阳性细胞率为68.33%,VEGF染色阳性细胞率为60.8%;鼻咽癌组织FDG摄取（SUVmax）和HK-Ⅱ表达的细胞阳性率呈显著相关（r=0.493,P＝0.001）,鼻咽癌组织FDG摄取（SUVmax）和VEGF表达的细胞阳性率相关（r=0.460,P＝0.03）。结论 鼻咽癌组织FDG摄取与HK-Ⅱ和VEGF过度表达相关。     

Glut-1、Glut-3在NSCLC和肺良性病变中的表达及其与FDG摄取的关系

背景与目的 葡萄糖转运蛋白是介导细胞葡萄糖摄取的主要载体.Glut-1、Glut-3的表达与组织的18F-2-脱氧葡萄糖(FDG)摄取有密切关系.本研究探讨NSCLC和肺良性病变中葡萄糖转运蛋白-1、3(Glut-1、Glut-3)的表达及其与FDG摄取之间的关系.方法 84例非小细胞肺癌(NSCLC)患者及24例肺良性病变患者术前行PET/CT检查,检测Glut-1、Glut-3的表达,并作相关分析.结果 84例NSCLC患者PET/CT检查平均SUV(SUVave)值为3.6-13.2,平均7.8±3.0.24例肺良性病变患者PET/CT检杏SUVave值为1.2-9.2,平均3.2±1.9.84例NSCLC患者Glut-1、Glut-3染色总分平均值分别为4.4±1.3和2.6±1.9.24例肺良性病变患者Glut-1、Glut-3染色总分平均值分别为0.9±0.9和1.2±1.4.NSCLC Glut-1、Glut-3的表达均较肺良性病变高(P<0.01).NSCLC中Glut-1的表达与FDG摄取呈正相关(r=0.78,P<0.01).肺良性病变中Glut-3的表达与FDG摄取呈正相关(r=0.45,P=0.03).结论 NSCLC和肺良性病变中均有Glut-1、Glut-3的过度表达.Glut-1表达可能与NSCLC中FDG摄取有关;Glut-3表达可能与肺良性病变FDG摄取有关.     

非小细胞肺癌中p53、Glut-1表达与FDG摄取的关系

目的:探讨非小细胞肺癌(NSCLC)中p53、葡萄糖转运蛋白-1(Glut-1)表达与氟脱氧葡萄糖(FDG)摄取三者之间的关系。方法:84例NSCLC患者术前行PET/CT检查,应用免疫组化法对肿瘤组织进行p53及Glut-1染色,并作相关分析。结果:平均标准化摄取值(SUVave)3.6-13.2,平均7.8±3.0。SUVave与Dmax、TNM分期、病理类型、分化程度均无相关性。Glut-1表达平均(4.4±1.3)分。p53染色阳性者41例(48.8%)。Glut-1表达与SUVave值之间呈正相关(r=0.78,P<0.01)。Glut-1与p53表达之间无相关性(P=0.37),SUVave值与p53表达之间亦无相关性(P=0.79)。结论:NSCLC细胞摄取FDG与Glut-1有关,但后者并非唯一因素。Glut-1调节与p53基因无关。     

早期鼻咽癌FDG摄取与葡萄糖易化扩散转运蛋白表达及放疗敏感性关系

头颈部肿瘤因肿瘤浸润范围和淋巴结转移情况决定了临床治疗方法的选择和配合，因此以FDG的摄取作为分期依据更为重要。近来研究发现多种肿瘤组织的葡萄糖易化扩散转运蛋白与FDG摄取关系密切，并与肿瘤对治疗的反应和预后有关。但在头颈部肿瘤中相关报道甚少，鼻咽癌方面未见报道。     

肺腺癌组织中PD-L1表达与18F-FDG摄取的相关性

目的 探讨肺腺癌组织中程序性细胞死亡蛋白配体-1（PD-L1）的表达与肿瘤组织18F-脱氧葡萄糖（¹⁸F-FDG）摄取的关系。方法 回顾性分析经病理证实的102例肺腺癌患者的临床资料，于治疗前行¹⁸F-FDG PET/CT检查，术后病理行免疫组织化学检测PD-L1表达情况，分析¹⁸F-FDG PET/CT最大标准摄取值（SUV_max）与PD-L1表达之间的关系。结果 102例患者中50例（49%）PD-L1阳性，阳性患者原发灶的SUVmax高于阴性患者（6.59±5.03 vs. 2.89±4.65, P=0.0001），用SUV_max预测PD-L1表达时，受试者工作特征曲线（ROC曲线）下面积是0.801（P=0.0001）；当SUVmax临界值为1.70时，约登指数最大为0.522。结论 肺腺癌原发灶FDG摄取与PD-L1表达存在相关性，PD-L1阳性更易发生在高SUVmax患者。     

移形上皮与鳞状上皮来源的恶性肿瘤摄取18F-FDG差异性的实验研究

[目的]探讨来自不同上皮来源的肿瘤组织葡萄糖代谢的差异,为临床PET/CT应用中如何判断上皮组织来源的恶性肿瘤葡萄糖摄取出现的假阳性和假阴性等问题提供理论依据.[方法] BALB/C裸鼠12只,随机分为2组,并且皮下分别接种膀胱癌EJ细胞和宫颈癌Hela细胞,1×106/0.2ml使其成瘤.行小动物PET扫描,取得葡萄糖标准化摄取值(SUV),测量SUVmax和SUVmean对肿瘤组织葡萄糖代谢进行评价.[结果]膀胱癌SUVmax:4.22±0.39,SUVmean:2.60±0.43;宫颈癌SUVmax:6.18±0.23,SUVmean:2.40±0.57.膀胱癌与宫颈癌的SUVmax值差异有统计学意义(t=-9.474,P＜0.01),而SUVmean值无统计学差异.[结论]鳞状上皮来源的肿瘤葡萄糖摄取要高于移形上皮来源的.     

细支气管肺泡癌的FDG-PET影像特点

目的研究细支气管肺泡癌对~(18)氟脱氧葡萄糖(FDG)的摄取特点。方法 1998年12月～2004年10月间,35例细支气管肺泡癌患者术前行FDG-正电子发射体层显像(PET)检查。PET结果用目测法与半定量分析方法判读。半定量分析方法中计算标准摄取值(SUV)。结果所有肿瘤都被FDG-PET探测到,目测法相应部位FDG不同程度浓聚。半定量分析细支气管肺泡癌组织的FDG摄取(SUVmax and SUVmean)高于相应的正常肺组织(SUVlung)(P＜0.001),SUVmax、SUVmean和SUVlung分别为3.14±1.65、2.40±1.34 和0.38±0.08。细支气管肺泡癌SUV与肿瘤大小正相关(P＜0.05)。21例(21／35,60.0％)SUVmean与15例(15／35,42.9％)SU Vmax低于2.5。这21例肿瘤全部被目测法与半定量分析判断为良性。结论 (1)细支气管肺泡癌组织的FDG摄取高于正常肺组织。(2)肿瘤FDG摄取与肿瘤大小有关。(3)很多细支气管肺泡癌病例 FDG-PET检查可呈现假阴性。     

非小细胞肺癌的CT征象与~(18)F-FDG PET表现、Glut1表达的关系

背景与目的 Glutl是介导葡萄糖转运的主要载体,同病灶对FDG的摄取程度呈正相关,但同肺癌CT征象的关系尚不十分清楚,本研究通过FDG PET/CT显像,筛选可以反映非小细胞肺癌葡萄糖代谢水平的CT征象和临床病理指标.方法 对33例肺癌(鳞癌11,腺癌22例)术前行PET/CT检查,收集病理类型、分化程度、有无淋巴结转移结果 ;评价CT征象(包括直径、深分叶征、细短毛刺征、棘突征、空泡征、血管集束征、胸膜凹陷征);视觉分析和SUVmax分析病灶对FDG的摄取程度;免疫组织化学SP法检测肿瘤组织Glutl的表达.结果 Glutl的阳性表达率为66.67%;鳞癌Glutl的阳性表达率和SUVmax明显高于腺癌(P双边=0.037,P单边=0.045);≥2cm组对FDG的摄取程度(视觉分析和SUVmax)和Glutl的阳性表达率明显高于<2cm组(P双边=0.002,P双边=0.001,P单边=0.049);视觉分析示有细短毛刺征组肺癌对FDG的摄取程度显著高于无细短毛刺征组(p双边=0.006).结论 肺癌的大小和细短毛刺征可反映肿瘤葡萄糖代谢水平,肺鳞癌的葡萄糖的代谢水平高于肺腺癌.     

Correlation of 18-F-fluorodeoxyglucose (FDG) accumulation with glucose transporter (Glut-1) expression in esophageal squamous cell carcinoma

BACKGROUND: We previously reported that positron emission tomography (PET) with 18-F-fluorodeoxyglucose (FDG) might be a useful tool for evaluating the stage of esophageal squamous cell carcinoma (SCC), and that FDG-PET shows greater accuracy in the diagnosis of lymph node metastasis than computed tomography. Further, we elucidated the relationships among FDG-PET performance, glucose transporter (Glut)-1 expression and serum levels of the tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA) and squamous cell carcinoma antigen (SCC-Ag) in esophageal SCC. PATIENTS AND METHODS: We studied 44 patients with thoracic esophageal SCC who had undergone radical esophagectomy. Immunohistochemical analysis was used to detect the expression of Glut-1 in resected specimens and FDG accumulation was assessed by FDG-PET scan. RESULTS: FDG uptake in the primary tumor was found in 34 out of 44 (77.3%) patients. No significant correlation was observed between SUVs and the tumor markers CEA, CYFRA and SCC-Ag. The survival rate in patients with high FDG uptake (SUV > 3) was significantly lower than in cases with low FDG uptake (SUV < 3) (p < 0.01). A significant correlation was observed between SUV and Glut-1 expression (p < 0.05). The prognosis in patients with both low Glut-1 expression and low FDG uptake tended to be more favorable than in patients with high Glut-1 expression and/or high FDG uptake. CONCLUSION: Glut-1 expression was related to FDG uptake, and assessment of both FDG uptake and Glut-1 expression might be useful for providing prognostic information in patients with esophageal SCC.     

Assessment of factors influencing FDG uptake in non-small cell lung cancer on PET/CT by investigating histological differences in expression of glucose transporters 1 and 3 and tumour size

Purpose

The objective of this study was to evaluate the major factors influencing on FDG uptake in non-small cell lung cancer (NSCLC) by investigating histological difference in the expression of glucose transporters 1 and 3 (Glut-1 and Glut-3) and tumour size.

Methods

This study enrolled 32 patients including 9 with squamous cell carcinoma (SCC) and 23 with adenocarcinoma (AC). The AC cases comprised 16 AC with mixed subtypes (AC-mixed) and 7 localized AC in situ (localized bronchioloalveolar carcinoma). Partial volume effect corrected maximum standardized uptake values (cSUVmax) and tumour size were obtained using FDG PET/CT. Glut-1 and Glut-3 expression were evaluated using five-point grading scales.

Results

Overexpression of Gluts was observed at high rates (88% for Glut-1 and 97% for Glut-3). They were mutually correlated. cSUVmax showed better correlation with size than with Gluts overexpression. AC and SCC showed a high positive expression rate for both Glut-1 and Glut-3, although the degree of overexpression was significantly higher in SCC than AC. In addition, localized AC in situ revealed a considerably higher positive expression rate and similar degrees of overexpression for both Glut-1 and Glut-3 compared with AC-mixed. By contrast, localized AC in situ alone was significantly smaller in both cSUVmax and size than either SCC or AC-mixed. No significant difference was found in cSUVmax or size between SCC and AC-mixed.

Conclusions

The FDG uptake of NSCLC might be dependent on size rather than on overexpression of Glut-1 or Glut-3. Low FDG uptake in localized AC in situ might result from its small size rather than Glut overexpression.     

Correlation of FDG-PET imaging with Glut-1 and Glut-3 expression in early-stage non-small cell lung cancer

PURPOSE: To correlate FDG activity on PET with the expression of glucose transporter proteins Glut-1 and Glut-3 in patients with early stage non-small cell lung cancer (NSCLC). METHODS: Over a 5 year period, all patients with a PET scan and clinical stage I NSCLC underwent an immunohistochemical analysis of their tumor for Glut-1 and Glut-3 expression. The amount of FDG uptake in the primary lesion was measured by a standardized uptake ratio (SUR) and correlated with immunohistochemical results. RESULTS: Seventy-three patients with a mean age of 66 years had clinical stage I disease. The final pathologic stage showed 64 patients with stage IA/B disease, eight with stage IIA disease, and one patient with pathologic stage IIIA (T1N2) disease. Glut-1 transporter expression was significantly higher than Glut-3 (P<0.0001), and although there was some association between the SUR and Glut-1 (P=0.085) and SUR and Glut-3 (P=0.074) expression, this did not reach statistical significance. CONCLUSIONS: Glut-1 and Glut-3 transporter expression did not demonstrate a statistically significant correlation with FDG uptake in potentially resectable lung cancer. It appears that these transporters alone do not affect the variation in FDG activity in early stage NSCLC.     

Correlation between FDG uptake and glucose transporter type 1 expression in neuroendocrine tumors of the lung

Neuroendocrine (NE) lung tumors are subdivided into the following types; typical (TC) and atypical carcinoids (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). Moreover, the determinants of the FDG uptakes of NE lung tumors have not been elucidated. Thus, the aim of the present study was to investigate the relationships between FDG uptake and glucose transporter type 1 (Glut-1) expression in these NE tumors. Tissue-proven NE lung tumor patients (n=32; age, mean+/-S.D.=67.8+/-10 years; male:female=28:4) who had undergone F-18 FDG-PET before treatment were enrolled in this study. There were 1 TC, 3 AC, 5 LCNEC, and 23 SCLC patients. FDG uptakes were quantified using maximum standardized uptake values (maxSUV). Paraffin sections of tumor tissues were immunostained using anti-Glut-1 antibody (Neomarkers, 1:50). Levels of Glut-1 expression are presented as percentages of tumor cells positively immunostained (%Glut-1). Relations between FDG uptakes and Glut-1 expression were assessed using Pearson correlation analysis. The maxSUVs of all NE lung tumors ranged from 0.6 to 29.5 (mean+/-S.D.=7.7+/-5.4) and %Glut-1 expression ranged from 0 to 100% (18+/-24%). The maxSUVs of all NE lung tumors were found to be significantly correlated with %Glut-1 expression (r=0.6471, p=0.0001). By subgroup analysis, maxSUV was also found to be significantly correlated with %Glut-1 expression in SCLC (n=23, r=0.6189, p=0.0016). FDG uptake was found to be highly correlated with Glut-1 expression in NE lung tumors. This result suggests that Glut-1 plays a crucial role in determining FDG uptake in these tumors.     

FDG uptake and glucose transporter type 1 expression in lymph nodes of non-small cell lung cancer.

AIMS: FDG uptake in NSCLC is related to glucose transporter type 1 (Glut-1) expression. Here, we investigated the direct causal relationship between FDG uptake and Glut-1 expression to determine the role of Glut-1 in FDG uptake by malignant and benign lymph nodes (LNs). METHODS: Fifty-five curative lung resections in 53 NSCLC patients (male:female=36:17, age=62.0+/-11.8 years) were included. Maximum standardized uptake values (maxSUVs) of LNs in preoperative whole body FDG-PET and Glut-1 immunostaining results were compared. RESULTS: Of 316 pathologically confirmed LNs, 12.3% (39/316) were malignant, and in malignant LNs, FDG positive LNs were no different from FDG negative LNs in terms of size (15.0+/-6.7 mm vs 10.0+/-6.1mm, p>0.05), or in terms of the proportion of LNs occupied by tumor (60.0+/-28.8% vs 39.2+/-38.4%, p>0.05), but had greater percentages of Glut-1 positive cells in tumors (74.1+/-31.8% vs 22.7+/-18.7%, p<0.01), and Glut-1 staining intensities (3.4+/-0.9 vs 1.8+/-1.3, p<0.01). FDG negative malignant LNs featured cytoplasmic Glut-1 expression and adenocarcinoma. Glut-1 staining intensities were found to be significantly correlated with the maxSUVs of malignant LNs (rho=0.516, p<0.05), but the percentages of Glut-1 positive cells in tumors were not (r=0.2072, p>0.05). Analysis of FDG positive benign LNs showed that maxSUV was not correlated with degree of follicular hyperplasia, or Glut-1 expression (p>0.05). CONCLUSIONS: Intense Glut-1 immunoreactivity was found to be proportionally related to the degree of FDG uptake by malignant LNs in NSCLC. However, the finding that Glut-1 expression in lymphoid hyperplasia showed no correlation with FDG uptake in benign LNs requires further investigation.     

Glut-1 glucose transporter expression in esophageal squamous cell carcinoma is associated with tumor aggressiveness

BACKGROUND: Glucose transporter (Glut) proteins, which are membrane proteins responsible for the transport of glucose across cellular membranes, have six forms. To further elucidate the role of Glut-1 expression in esophageal squamous cell carcinoma, we examined the expression of Glut-1 protein immunohistochemically. MATERIALS AND METHODS: Immunohistochemical expression of Glut-1 was examined in surgically resected tissues from 95 patients with esophageal squamous cell carcinoma. RESULTS: Of the 95 esophageal carcinomas, 91 (95.8%) had some Glut-1 immunostaining in the membranes of the cancer cells. Positive staining (> 30% of cancer cells showing Glut-1 expression) was observed in 49 (51.6%) of the cases. Comparison of Glut-1 expression and clinicopathological characteristics in the 95 patients with esophageal cancer revealed significant associations between Glut-1 expression and tumor status (p < 0.001), lymph node status (p < 0.05), metastatic status (p < 0.01), and pathological stage (p < 0.001). The survival rates of patients with Glut-1-positive tumors were significantly lower than those of patients with Glut-1-negative tumors (log-rank p < 0.05). CONCLUSION: In conclusion, the level of Glut-1 expression may be a useful marker that can provide information on tumor aggressiveness and prognosis in patients with esophageal squamous cell carcinoma.     

Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma

BACKGROUND: The overexpression of glucose transporters, especially of Glut-1, is a common characteristic of human malignancies, including head and neck carcinoma. Recently, the assessment of glucose metabolism in the tumor with [(18)F]-2-fluoro-2 deoxy-D-glucose (FDG) and positron emission tomography (FDG-PET) has been used to identify particularly aggressive tumors. The authors tested the hypothesis that both glucose transport and its metabolism play a key role in the progression of oral squamous cell carcinoma (OSCC). METHODS: Retrospective analysis of Glut-1 expression was performed by immunohistology in 118 patients with OSCC, and a Glut-1 labeling index (LI) was established for each. A separate group of 44 patients with primary OSCC was evaluated prospectively by FDG-PET prior to surgery. To link the expression of Glut-1 with glucose metabolism, both FDG-PET and immunohistology were determined in a subgroup of 31 patients, and the results were correlated with overall survival. RESULTS: The patients who had OSCC with a low LI for Glut-1 survived significantly longer compared with patients who had OSCC with a high LI (138 months vs. 60 months; P = 0.0034). It was found that Glut-1 expression was an independent marker of prognosis in patients with OSCC. In patients who were evaluated by FDG-PET, the standardized uptake value (SUV) below the median split value of 5.6 was predictive of a longer survival (P < 0.027), whereas an SUV > 5.6 was associated with an increased hazard of death. In combination, a high Glut-1 level and a high SUV predicted shorter survival (P < 0.005) for patients with OSCC. Patients who achieved a complete response to preoperative radiation tended to have tumors with low glucose metabolism, as defined by both the Glut-1 LI and the SUV. CONCLUSIONS: Both glucose transport and glucose metabolism determine the glycolytic tumor phenotype, which is a significant negative biomarker of prognosis and overall survival in patients with OSCC.