Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer.
BACKGROUND
The chemotherapy resistance of non-small cell lung cancer (NSCLC) remains a clinic challenge and is closely associated with several biomarkers including epidermal growth factor receptor (EGFR) ( Drugs 72(Suppl 1):28-36, 012.), p53 ( Med Sci Monit 11(6):HY11-HY20, 2005.) and excision repair cross complementing gene 1 (ERCC1) ( J Thorac Oncol 8(5):582-586, 2013.). Fluorodeoxyglucose positron emission tomography (FDG-PET) is the best non-invasive surrogate for tumor biology with the maximal standardized uptake values (SUVmax) being the most important paradigm. However, there are limited data correlating FDG-PET with the chemotherapy resistant tumor markers. The purpose of this study was to determine the correlation of chemotherapy related tumor marker expression with FDG-PET SUVmax in NSCLC.


METHODS
FDG-PET SUVmax was calculated in chemotherapy naïve patients with NSCLC (n=62) and immunohistochemical analysis was performed for EGFR, p53 or ERCC1 on the intraoperative NSCLC tissues. Each tumor marker was assessed independently by two pathologists using common grading criteria. The SUVmax difference based on the histologic characteristics, gender, differentiation, grading and age as well as correlation analysis among these parameters were performed. Multiple stepwise regression analysis was further performed to determine the primary predictor for SUVmax and the receiver operating characteristics (ROC) curve analysis was performed to detect the optimized sensitivity and specificity for SUVmax in suggesting chemotherapy resistant tumor markers.


RESULTS
The significant tumor type (P=0.045), differentiation (P=0.021), p53 (P=0.000) or ERCC1 (P=0.033) positivity dependent differences of SUVmax values were observed. The tumor differentiation is significantly correlated with SUVmax (R=-0.327), tumor size (R=-0.286), grading (R=-0.499), gender (R=0.286) as well as the expression levels for p53 (R= -0.605) and ERCC1 (R=-0.644). The expression level of p53 is significantly correlated with SUVmax (R=0.508) and grading (R=0.321). Furthermore, multiple stepwise regression analysis revealed that p53 expression was the primary predictor for SUVmax. When the cut-off value of SUVmax was set at 5.15 in the ROC curve analysis, the sensitivity and specificity of SUVmax in suggesting p53 positive NSCLC were 79.5% and 47.8%, respectively.


CONCLUSIONS
The current study suggests that SUVmax of primary tumor on FDG-PET might be a simple and good non-invasive method for predicting p53-related chemotherapy resistance in NSCLC when we set the cu-off value of SUVmax at 5.15.
PET-CT Center, the First Affiliated Hospital, Medical School, Xi'an Jiaotong University, No,277 West Yanta road, Xi'an, Shaanxi 710061, People's Republic of China. duanxy@mail.xjtu.edu.cn.
Xiao-Yi
XY
Duan
Wen
W
Wang
Jian-Sheng
JS
Wang
Jin
J
Shang
Jun-Gang
JG
Gao
You-Min
YM
Guo
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D012372:ROC Curve; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D019788:Fluorodeoxyglucose F18; C071447:ERCC1 protein, human; D004720:Endonucleases