JTCS KCI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Philip W. Smith
Benjamin D. Kozower
Christine L. Lau
David R. Jones
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Taylor, M. D.
Right arrow Articles by Jones, D. R.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Taylor, M. D.
Right arrow Articles by Jones, D. R.
Related Collections
Right arrow Lung - cancer

J Thorac Cardiovasc Surg 2009;137:43-48
© 2009 The American Association for Thoracic Surgery

General Thoracic Surgery

Fluorodeoxyglucose positron emission tomography and tumor marker expression in non–small cell lung cancer

Matthew D. Taylor, MDa, Philip W. Smith, MDa, William K. Brix, MDb, Mark R. Wick, MDb, Nicholas Theodosakisa, Brian R. Swenson, MD, MSa, Benjamin D. Kozower, MDa, Christine L. Lau, MDa, David R. Jones, MDa,*

a Department of Surgery, University of Virginia, Charlottesville, Va
b Department of Pathology, University of Virginia, Charlottesville, Va

Received for publication June 24, 2008; revisions received September 18, 2008; accepted for publication October 13, 2008.

* Address for reprints: David R. Jones, MD, Professor of Surgery, University of Virginia, Department of Surgery, Box 800679, Charlottesville, VA 22908-0679. (Email: djones{at}virginia.edu).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 Appendix
 References
 
Objective: The best current noninvasive surrogate for tumor biology is fluorodeoxyglucose positron emission tomography (FDG–PET). Both FDG–PET maximal standardized uptake values and selected tumor markers have been shown to correlate with stage, nodal disease, and survival in non–small cell lung cancer (NSCLC). However, there are limited data correlating FDG–PET with tumor markers. The purpose of this study was to determine the correlation of tumor marker expression with FDG–PET maximal standardized uptake values in NSCLC.

Methods: FDG–PET maximal standardized uptake values were calculated in patients with NSCLC (n = 149). No patient had induction chemoradiotherapy. Intraoperative NSCLC tissue was obtained and tissue microarrays were created. Immunohistochemical analysis was performed for 5 known NSCLC tumor markers (glucose transporter 1, p53, cyclin D1, epidermal growth factor receptor, and vascular endothelial growth factor). Each tumor marker was assessed independently by two pathologists using common grading criteria. Subgroup analysis based on histologic characteristics and regional nodal status was performed.

Results: FDG–PET correlated with T classification (P < .0001), N stage (P = .002), and greatest tumor dimension (P < .0001). In addition, increasing maximal standardized uptake values correlated with increased expression of glucose transporter 1 (P < .0001) and p53 (P = .04) in adenocarcinoma. Epidermal growth factor receptor expression correlated with maximal standardized uptake values without predilection for histologic subtype (P = .004).

Conclusion: FDG–PET maximal standardized uptake values correlate with an increased expression of glucose transporter 1 and p53 in lung adenocarcinoma, but not squamous cell cancer. Future studies attempting to correlate FDG–PET with tumor biology will need to consider the effect of different tumor histologic types.

Abbreviations and Acronyms CT = computed tomography; EGFR = epidermal growth factor receptor; FDG = F-deoxyglucose; FDG–PET = fluorodeoxyglucose positron emission tomography; GLUT-1 = glucose transporter 1; NSCLC = non–small cell lung cancer; SUVmax = maximal standardized uptake values; VEGF = vascular endothelial growth factor


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 Appendix
 References
 
Fluorodeoxyglucose positron emission tomography (FDG–PET) has become an important tool in the armamentarium of clinicians for diagnosing and staging of non–small cell lung cancer (NSCLC). FDG–PET maximal standardized uptake values (SUVmax) of primary tumors have been shown to correlate with both stage and nodal disease in NSCLC.1Go Furthermore, tumor FDG–PET SUVmax have been shown to predict survival in patients with NSCLC.2Go

Although the classic TNM staging system includes widely known prognostic pathologic factors of NSCLC, this system provides no assessment of the biologic or molecular events leading to the development and progression of lung cancer. Molecular pathology has provided considerable information regarding the differential expression of gene products associated with lung carcinogenesis. A recent meta-analysis of immunohistochemical studies investigating tumor marker expression and its correlation to survival in NSCLC found 17 significant tumor markers that have been investigated by eight or more research groups.3Go With the advent of therapies directed at specific molecular pathways such as epidermal growth factor receptor (EGFR) inhibitors and anti–vascular endothelial growth factor (VEGF) antibodies, analysis of the relationship of molecular markers to diagnostic methods, such as FDG–PET, used to assess treatment response and to provide prognostic information is clearly needed.

Although glucose metabolism is the central factor for increased FDG uptake in tumor cells, very few studies have investigated the correlation of FDG uptake with lung cancer tumor marker expression. The 5 tumor markers selected for evaluation in this study were glucose transporter 1 (GLUT-1), p53, EGFR, VEGF, and cyclin D1. We selected these markers inasmuch as there is ample evidence in the literature suggesting their importance in the development and progression of lung cancer.4-13Go

The purpose of this study is to examine the correlation of selective tumor marker expression to FDG–PET, the best-known noninvasive surrogate marker of tumor biology. We hypothesize that some or all of these 5 tumor markers will correlate with SUVmax in NSCLC specimens. Subgroup analysis of patients by locoregional nodal status and histologic characteristics will determine whether expression patterns of the selected tumor markers and FDG–PET are different. Collectively, these studies will offer insight into the correlative relationships between expression of these specific tumor markers and FDG–PET in NSCLC.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 Appendix
 References
 
Patients
Paraffin-embedded primary lung tumor samples and patient-matched normal lung tissue in 149 consecutive patients were collected between January 2005 and October 2006. Approval for collection of the patient tissue was obtained from the Institutional Review Board for Health Science Research at the University of Virginia. Individual patient consent was obtained for procurement of tissue for research purposes before patients underwent surgery. Clinicopathologic data were collected from our general thoracic surgery database. Of the 149 patients, 56% had their FDG–PET scan performed and interpreted at the University of Virginia with a dedicated fusion positron emission tomography/computed tomography (PET/CT) scanner. The remaining 44% of patients had their FDG–PET imaging performed at an outside institution with interpretation of the studies independently performed by our nuclear radiologists at the University of Virginia.

Preparation of the Tissue Microarrays
All tumor slides were reviewed for tumor type and grade by two pathologists. A representative slide and the corresponding block of formalin-fixed paraffin-embedded tissue were selected. For each case, three 1-mm cores of tumor and one core of uninvolved epithelium were removed from the original block and embedded in a paraffin block with a specialized manual arraying instrument (model MTA1; Beecher Instruments, Sun Prairie, Wis).

Immunohistochemical Analysis
A tissue microarray was constructed for immunohistochemical studies that evaluated p53, VEGF, EGFR, cyclin-D1, and GLUT-1. Information for the antibody, antigen retrieval mechanism, and staining pattern are shown in Appendix Table 1 . Unstained tissue was used as the negative control. Positive controls are as follows: p53–human lymph node, EGFR–human placenta, GLUT-1–human red blood cells, cyclin D1–human tonsil, and VEGF–colon cancer. Immunohistochemical staining was scored by calculating the percentage of cells staining positive and by assessing the intensity of immunohistochemical staining. Immunohistochemical intensity was scored as 0 = none, 1 = weak, 2 = moderate, and 3 = intense. The product of each tumor marker's immunohistochemical staining was then calculated by multiplying the percentage of positive cells by the staining intensity.14Go Product scores ranged from 0% to 300%.


View this table:
[in this window]
[in a new window]

  		Table 1 Patient demographics
 
Statistical Analysis
Statistical analysis was performed with SAS version 9.1 for Windows software (SAS Institute, Inc, Cary, NC). All P values were calculated with the Spearman rank correlation test and the 2-tailed Student t test for continuous variables.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 Appendix
 References
 
One hundred forty-nine patients were included in this study. The demographic characteristics of the population are shown in Table 1.

Table 2 illustrates the selected tumor marker correlation coefficients to SUVmax and the respective P values. FDG-SUVmax correlated with greatest tumor dimension, T classification, and N classification. There was a positive correlation of increasing SUVmax and increased expression of GLUT-1 and EGFR in all NSCLC samples. Figure 1 illustrates the expression patterns of these 2 tumor markers in primary lung cancer specimens. Cyclin D1, p53, and VEGF expression did not correlate with SUVmax for our cohort of patients.


View this table:
[in this window]
[in a new window]

  		Table 2 Correlation between FDG-SUVmax and tumor marker expression and pathologic stage in all patients with NSCLC (n = 149), lung adenocarcinoma (n = 68), and squamous carcinoma (n = 64)
 

Figure 1
View larger version (141K):
[in this window]
[in a new window]

  		Figure 1. NSCLC tissue microarray. A, Representative 2x magnification tissue microarray of GLUT-1 expression in NSCLC demonstrates differential expression patterns between patient tumor samples. B, Representative 20x magnification illustrating diffuse GLUT-1 expression in NSCLC. C, Representative 10x magnification tissue microarray of EGFR expression in lung adenocarcinoma. D, Representative 10x magnification tissue microarray of EGFR expression in lung squamous carcinoma. NSCLC, Non–small cell lung cancer; GLUT-1, glucose transporter 1; EGFR, epidermal growth factor receptor.

 
NSCLC specimens were next stratified by histologic subtype (adenocarcinoma [n = 68] or squamous [n = 64]) to determine whether the correlation of SUVmax to tumor markers differed by tumor histology. Table 2 shows correlation coefficients of SUVmax with the 5 tumor markers for adenocarcinoma and squamous carcinoma. In adenocarcinoma specimens, GLUT-1 expression strongly correlated with SUVmax, in contrast to squamous histology, in which no significant correlation was found. Also, p53 was found to correlate with SUVmax in adenocarcinoma but not in squamous carcinoma. Furthermore, EGFR expression, found to correlate with SUVmax in the entire cohort, did not reach statistical significance when stratifying by histologic subtype.

We next stratified all patents by FDG-SUVmax and sought to determine whether there was a value that correlated with a significant difference in tumor marker expression. These results are shown in Table 3 . Given that SUVmax less than 2.5 in lung tumors are less indicative of malignancy, we used these values as our control group.15Go We noted a stepwise increase in the percentage of patients with positive regional nodes who had increasing SUVmax. GLUT-1 expression within tumor specimens was significantly higher in patients with SUVmax greater than 10 compared with patients with SUVmax of 2.5 or less. Furthermore, EGFR expression was found to be significantly greater in patients with primary tumor SUVmax greater than 2.5 compared with tumors with SUVmax less than 2.5.


View this table:
[in this window]
[in a new window]

  		Table 3 FDG–PET SUVmax and tumor marker expression
 
The percentage of NSCLC that had expression of the selected tumor markers and the corresponding mean SUVmax based on regional nodal status is shown in Table 4 . SUVmax was significantly greater for tumors with regional node–positive disease (6.4 ± 0.5 vs 8.5 ± 0.6; P = .005). GLUT-1 expression was found in a significantly greater proportion of tumors with associated regional nodal disease as compared with GLUT-1 expression in tumors without nodal disease. In the proportion of tumors demonstrating expression of GLUT-1, p53, and cyclin D1, SUVmax was significantly greater in the tumors with associated regional nodal disease than in those with node-negative disease.


View this table:
[in this window]
[in a new window]

  		Table 4 Tumor marker expression and SUVmax by nodal status
 

   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
Appendix
 References
 
This study investigates the correlation of 5 tumor markers in lung cancer with the best noninvasive method of assessing tumor biology, FDG–PET. Previous studies have demonstrated the correlation of FDG–PET SUVmax with survival in patients with lung cancer.2,16Go

GLUT-1 overexpression, the human erythrocyte glucose transporter, has been correlated with a poor prognosis in patients with lung cancer.17Go Increased glucose uptake in tumor cells is thought to be regulated by glucose transporter activity.5Go In our study, SUVmax was found to positively correlate with the expression of GLUT-1 in NSCLC and specifically adenocarcinoma. These results support similar findings reported in other studies.18,19Go In addition, we demonstrated that the percentage of positive GLUT-1 tumor cells was significant higher between those patients with primary tumor SUVmax greater than 10 when compared with those with values less than 2.5. Stratifying this group of patients with lung cancer by regional nodal status, we found that the number of lung cancers expressing GLUT-1 was significantly higher in specimens with concurrent regional nodal disease. Furthermore, SUVmax of these GLUT-1 positive tumors with regional nodal disease was significantly greater than SUVmax for node-negative tumors. One previous study demonstrated a correlation of GLUT-1 expression in primary lung tumor with metastatic lymph nodes; however, no comparison was made between GLUT-1 expression of the tumor and its nodal status.20Go

Alterations of tumor suppressor genes such as p53 by mutation or overexpression are frequently found in lung carcinoma, with many studies, although not all, suggesting that is associated with a poor prognosis.6,11,13Go Our analysis of p53 expression in NSCLC, demonstrated a significant correlation of p53 overexpression with SUVmax in lung adenocarcinoma. This is the first larger cohort study demonstrating a correlation between p53 expression and SUVmax in lung cancer. SUVmax of p53 immunopositive tumors with regional nodal disease were significantly greater than SUVmax for node-negative tumors. We did not find a significant increase in the number of NSCLCs expressing p53 on the basis of regional nodal status. Aberrant expression of p53 in NSCLC has been associated with an increased likelihood of mediastinal nodal metastasis.21Go The discrepancy between our results and that study may be related to the 3-fold higher representation of pathologic stage III and IV disease in that study.

EGFR expression appears to have moderate prognostic value in NSCLC.9Go Specific EGFR-activating mutations within lung tumors have been associated with a dramatically improved response to EGFR inhibitors in early-phase clinical trials.22Go EGFR expression was found to correlate to SUVmax in the entire cohort; however, statistical significance was not obtained when the specimens were examined by histologic subtype. This discrepancy is likely a result of the reduction in sample size associated with stratification. Also, this study illustrated that EGFR expression was significantly greater in NSCLC with SUVmax greater than 2.5. These results support the clinical utility of FDG–PET as a means of assessing response to EGFR inhibitor therapy, as suggested by other groups.22Go We did not find a significant difference in EGFR expression on the basis of tumor nodal status. Additionally, SUVmax of EGFR-positive tumors with regional nodal disease were not found to be greater for similar tumors without nodal disease. Fontanini and associates23Go found a correlation of EGFR expression in primary squamous cell lung cancers with the presence of node-positive disease. However, this correlation was not found in patients with lung adenocarcinoma. Our study had an equal number of patients with squamous and adenocarcinoma histologic features, and there were fewer patient samples examined, both of which may account for the discrepancy between our study and that one.

Cyclin D1, an important cell cycle regulator, is translocated to the cell nucleus when exposed to tobacco carcinogens, and this nuclear accumulation induces uncontrolled cell proliferation.7Go Cyclin D1 overexpression has been demonstrated in NSCLC compared with normal lung tissue.4Go SUVmax did not correlate with the expression of cyclin D1. Other studies have reported similar findings.24Go We also did not find a significant difference in cyclin D1 expression based on tumor nodal status. However, SUVmax in cyclin D1–positive tumors with regional node–positive disease was significantly greater than in tumors without nodal disease. Cyclin D1 overexpression in NSCLC has been associated with lymph node metastasis.25Go Closer inspection of these data supports that cyclin D1 overexpression and nodal disease were significantly stronger for stage III (P = .001) versus stage I or II (P = .048) disease. In this study 41% of patients had stage III disease, whereas in our study only 13% had stage III disease.

VEGF plays a critical role in tumor angiogenesis and metastasis in NSCLC. Studies have demonstrated overexpression of VEGF in NSCLC.8,10Go A recent review of angiogenesis in NSCLC uncovered 16 studies highlighting the prognostic significance of VEGF overexpression in lung cancer.26Go VEGF expression did not correlate with SUVmax in our population. Our study is the first to define the relationship of VEGF expression to FDG–PET in lung cancer. Stratification by regional nodal disease found no significant difference in VEGF expression based on tumor nodal status. However, an insignificant trend favoring increased SUVmax of VEGF-positive tumors with nodal disease compared with similar tumors with node-negative disease was noted. Previous studies investigating the correlation of VEGF expression in NSCLC and the presence of nodal disease have had discordant conclusions.27-30Go Therefore, in this complex milieu of growth factors, VEGF expression alone in lung tumors is unlikely to predict the presence of lymph node metastasis.

Limitations of this study include the limited sample size used. A larger sample size may elucidate further relationships between FDG–PET and the investigated tumor markers. Second, use of tissue microarrays in which small tissue cylinders are studied may not in fact adequately represent the entire specimen owing to tissue heterogeneity. Third, despite our efforts to use a well-established protocol, inherent drawbacks of immunohistochemical analysis include interlaboratory differences in antigen retrieval, staining protocols, and antibodies used. A fourth limitation is that PET/CT imaging was performed on multiple scanners, which could influence the interpretation of SUVmax. We attempted to address this by having our nuclear radiologists interpret the images at our institution.

Future study directions will evaluate expression of these tumor markers at a transcriptional level using a more sensitive method, quantitative real-time polymerase chain reaction. This investigation will use cryopreserved lung tumors, thereby circumventing the potential pitfall of using paraffin-embedded tissue for the assessment of transcriptional regulation.

In conclusion, GLUT-1 and EGFR expression in primary NSCLC correlates with FDG-SUVmax. The correlation between SUVmax and GLUT-1 expression is significantly stronger in lung adenocarcinoma. Additionally, p53 expression significantly correlated with SUVmax in lung adenocarcinoma. GLUT-1 expression in NSCLC is significantly greater in patients with regional mediastinal nodal disease. In tumors expressing GLUT-1, p53, and cyclin D1, SUVmax was significantly greater in patients with regional nodal disease. Finally, the correlation of EGFR expression with FDG–PET in lung cancer suggests potential clinical utility in monitoring response to EGFR inhibitor therapy. In contrast, a lack of correlation between FDG–PET and VEGF expression points to limited utility of FDG–PET to assess clinical response of lung adenocarcinoma to anti-VEGF therapies.


   Appendix
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Appendix
References
 

Table 1 Antibodies for immunohistochemical analysis
Antibody Company Catalog No. Type Clone Dilution Antigen retrieval Positive staining pattern
VEGF DAKO M7273 Monoclonal mouse VG1 1/6400 Citrate buffer Cytoplasmic
EGFR DAKO M3563 Monoclonal mouse H11 1/400 Citrate buffer Cytoplasmic
p53 DAKO M7001 Monoclonal mouse DO-7 1/50 Citrate buffer Nuclear
GLUT-1 DAKO A3536 Polyclonal rabbit Not available 1/300 Citrate buffer Cytoplasmic membrane
Cyclin D1 DAKO M7155 Monoclonal mouse DCS-6 1/50 Citrate buffer Nuclear

VEGF, Vascular endothelial growth factor; EGFR, epidermal growth factor receptor; GLUT-1, glucose transporter 1.


   Footnotes
 
Read at the Thirty-fourth Annual Meeting of The Western Thoracic Surgical Association, Kona, Hawaii, June 25–28, 2008.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Appendix
 References
 

  1. Vansteenkiste JF, Stroobants SG, Dupont PJ, De Leyn PR, Verbeken EK, Deneffe GJ, et al. Prognostic importance of the standardized uptake value on (18)F-fluoro-2-deoxy-glucose–positron emission tomography scan in non-small-cell lung cancer: An analysis of 125 cases. Leuven Lung Cancer Group. J Clin Oncol 1999;17:3201-3206.[Abstract/Free Full Text]
  2. Cerfolio RJ, Bryant AS, Ohja B, Bartolucci AA. The maximum standardized uptake values on positron emission tomography of a non–small cell lung cancer predict stage, recurrence, and survival. J Thorac Cardiovasc Surg 2005;130:151-159.[Abstract/Free Full Text]
  3. Zhu CQ, Shih W, Ling CH, Tsao MS. Immunohistochemical markers of prognosis in non–small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J Clin Pathol 2006;59:790-800.[Abstract/Free Full Text]
  4. Betticher DC, Heighway J, Hasleton PS, Altermatt HJ, Ryder WD, Cerny T, et al. Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer. Br J Cancer 1996;73:294-300.[Medline]
  5. Flier JS, Mueckler MM, Usher P, Lodish HF. Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science 1987;235:1492-1495.[Abstract/Free Full Text]
  6. Fujino M, Dosaka-Akita H, Harada M, Hiroumi H, Kinoshita I, Akie K, et al. Prognostic significance of p53 and ras p21 expression in nonsmall cell lung cancer. Cancer 1995;76:2457-2463.[Medline]
  7. Gautschi O, Ratschiller D, Gugger M, Betticher DC, Heighway J. Cyclin D1 in non–small cell lung cancer: a key driver of malignant transformation. Lung Cancer 2007;55:1-14.[Medline]
  8. Kajita T, Ohta Y, Kimura K, Tamura M, Tanaka Y, Tsunezuka Y, et al. The expression of vascular endothelial growth factor C and its receptors in non–small cell lung cancer. Br J Cancer 2001;85:255-260.[Medline]
  9. Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer 2001;37(Suppl. 4):S9-S15.[Medline]
  10. Niklinska W, Burzykowski T, Chyczewski L, Niklinski J. Expression of vascular endothelial growth factor (VEGF) in non–small cell lung cancer (NSCLC): association with p53 gene mutation and prognosis. Lung Cancer 2001;34(Suppl. 2):S59-S64.
  11. Quinlan DC, Davidson AG, Summers CL, Warden HE, Doshi HM. Accumulation of p53 protein correlates with a poor prognosis in human lung cancer. Cancer Res 1992;52:4828-4831.[Abstract/Free Full Text]
  12. Sunaga N, Oriuchi N, Kaira K, Yanagitani N, Tomizawa Y, Hisada T, et al. Usefulness of FDG–PET for early prediction of the response to gefitinib in non–small cell lung cancer. Lung Cancer 2008;59:203-210.[Medline]
  13. Takahashi T, Nau MM, Chiba I, Birrer MJ, Rosenberg RK, Vinocour M, et al. p53: a frequent target for genetic abnormalities in lung cancer. Science 1989;246:491-494.[Abstract/Free Full Text]
  14. Lagendijk JH, Mullink H, van Diest PJ, Meijer GA, Meijer CJ. Immunohistochemical differentiation between primary adenocarcinomas of the ovary and ovarian metastases of colonic and breast origin. Comparison between a statistical and an intuitive approach. J Clin Pathol 1999;52:283-290.[Abstract]
  15. Al-Sugair A, Coleman RE. Applications of PET in lung cancer. Semin Nucl Med 1998;28:303-319.[Medline]
  16. Ahuja V, Coleman RE, Herndon J, Patz Jr. EF. The prognostic significance of fluorodeoxyglucose positron emission tomography imaging for patients with nonsmall cell lung carcinoma. Cancer 1998;83:918-924.[Medline]
  17. Younes M, Brown RW, Stephenson M, Gondo M, Cagle PT. Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival. Cancer 1997;80:1046-1051.[Medline]
  18. de Geus-Oei LF, van Krieken JH, Aliredjo RP, Krabbe PF, Frielink C, Verhagen AF, et al. Biological correlates of FDG uptake in non-small cell lung cancer. Lung Cancer 2007;55:79-87.[Medline]
  19. van Baardwijk A, Dooms C, van Suylen RJ, Verbeken E, Hochstenbag M, Dehing-Oberije C, et al. The maximum uptake of (18)F-deoxyglucose on positron emission tomography scan correlates with survival, hypoxia inducible factor-1alpha and GLUT-1 in non–small cell lung cancer. Eur J Cancer 2007;43:1392-1398.[Medline]
  20. Nguyen XC, So Y, Chung JH, Lee WW, Park SY, Kim SE. High correlations between primary tumours and loco–regional metastatic lymph nodes in non-small-cell lung cancer with respect to glucose transporter type 1-mediated 2-deoxy-2-F18-fluoro-D-glucose uptake. Eur J Cancer 2008;44:692-698.[Medline]
  21. Tanaka F, Yanagihara K, Otake Y, Li M, Miyahara R, Wada H, et al. Biological features and preoperative evaluation of mediastinal nodal status in non–small cell lung cancer. Ann Thorac Surg 2000;70:1832-1838.[Abstract/Free Full Text]
  22. Sunaga N, Tomizawa Y, Yanagitani N, Iijima H, Kaira K, Shimizu K, et al. Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non–small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy. Lung Cancer 2007;56:383-389.[Medline]
  23. Fontanini G, Vignati S, Bigini D, Mussi A, Lucchi H, Angeletti CA, et al. Epidermal growth factor receptor (EGFr) expression in non–small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype. Eur J Cancer 1995;31A:178-183.
  24. Watanabe K, Nomori H, Ohtsuka T, Naruke T, Ebihara A, Orikasa H, et al. [F-18]Fluorodeoxyglucose positron emission tomography can predict pathological tumor stage and proliferative activity determined by Ki-67 in clinical stage IA lung adenocarcinomas. Jpn J Clin Oncol 2006;36:403-409.[Abstract/Free Full Text]
  25. Keum JS, Kong G, Yang SC, Shin DH, Park SS, Lee JH, et al. Cyclin D1 overexpression is an indicator of poor prognosis in resectable non–small cell lung cancer. Br J Cancer 1999;81:127-132.[Medline]
  26. Bremnes RM, Camps C, Sirera R. Angiogenesis in non–small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer 2006;51:143-158.[Medline]
  27. Yuan A, Yu CJ, Chen WJ, Lin FY, Kuo SH, Luh KT, et al. Correlation of total VEGF mRNA and protein expression with histologic type, tumor angiogenesis, patient survival and timing of relapse in non-small-cell lung cancer. Int J Cancer 2000;89:475-483.[Medline]
  28. Arinaga M, Noguchi T, Takeno S, Chujo M, Miura T, Uchida Y. Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in patients with nonsmall cell lung carcinoma. Cancer 2003;97:457-464.[Medline]
  29. Ogawa E, Takenaka K, Yanagihara K, Kurozumi M, Manabe T, Wada H, et al. Clinical significance of VEGF-C status in tumour cells and stromal macrophages in non–small cell lung cancer patients. Br J Cancer 2004;91:498-503.[Medline]
  30. Takizawa H, Kondo K, Fujino H, Kenzaki K, Miyoshi T, Sakiyama S, et al. The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non–small cell lung cancer. Br J Cancer 2006;95:75-79.[Medline]



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
K. Shimizu, Y. Hirami, S. Saisho, T. Yukawa, A. Maeda, K. Yasuda, and M. Nakata
Maximal Standardized Uptake Value on FDG-PET Is Correlated With Cyclooxygenase-2 Expression in Patients With Lung Adenocarcinoma
Ann. Thorac. Surg., February 1, 2012; 93(2): 398 - 403.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
K. Kaira, M. Endo, M. Abe, K. Nakagawa, Y. Ohde, T. Okumura, T. Takahashi, H. Murakami, A. Tsuya, Y. Nakamura, et al.
Biologic Correlation of 2-[18F]-Fluoro-2-Deoxy-D-Glucose Uptake on Positron Emission Tomography in Thymic Epithelial Tumors
J. Clin. Oncol., August 10, 2010; 28(23): 3746 - 3753.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Philip W. Smith
Benjamin D. Kozower
Christine L. Lau
David R. Jones
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Taylor, M. D.
Right arrow Articles by Jones, D. R.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Taylor, M. D.
Right arrow Articles by Jones, D. R.
Related Collections
Right arrow Lung - cancer

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS