Kang, Shin-Myung
(Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Koh, Won-Jung
(Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Suh, Gee-Young
(Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Chung, Man-Pyo
(Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Han, Joung-Ho
(Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Kim, Ho-Joong
(Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Kwon, O-Jung
(Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Um, Sang-Won
(Division of Pulmonary and Critical Care Medicine)
Background: Recent evidences have revealed metabolic functions of p53 in cancer cells; adaptation or survival to metabolic stress and metabolic shift toward oxidative phosphorylation. However, further studies in clinical setting are needed. We investigated whether p53 protein expression, as a surrog...
Background: Recent evidences have revealed metabolic functions of p53 in cancer cells; adaptation or survival to metabolic stress and metabolic shift toward oxidative phosphorylation. However, further studies in clinical setting are needed. We investigated whether p53 protein expression, as a surrogate marker for loss of p53 function, is associated with metabolic features of stage I non-small cell lung cancer (NSCLC), focusing on tumor necrosis and maximal standardized uptake value (SUVmax) on $^{18}F$-fluorodeoxyglucose positron emission tomography. Methods: Clinical information was obtained from retrospective review of medical records. p53 expression was assessed by immunohistochemical staining. Results: p53 protein expression was detected in 112 (46%) of 241 NSCLC cases included in this study. p53 expression was independently associated with the presence of necrosis (odds ratio [OR], 2.316; 95% confidence interval [CI], 1.215~4.416; p=0.011). Non-adenocarcinoma histology (OR, 8.049; 95% CI, 4.072~15.911; p<0.001) and poorly differentiation (OR, 6.474; 95% CI, 2.998~13.979; p<0.001) were also independently associated with the presence of necrosis. However, p53 expression was not a significant factor for SUVmax. Conclusion: p53 protein expression is independently associated with the presence of necrosis, but not SUVmax.
Background: Recent evidences have revealed metabolic functions of p53 in cancer cells; adaptation or survival to metabolic stress and metabolic shift toward oxidative phosphorylation. However, further studies in clinical setting are needed. We investigated whether p53 protein expression, as a surrogate marker for loss of p53 function, is associated with metabolic features of stage I non-small cell lung cancer (NSCLC), focusing on tumor necrosis and maximal standardized uptake value (SUVmax) on $^{18}F$-fluorodeoxyglucose positron emission tomography. Methods: Clinical information was obtained from retrospective review of medical records. p53 expression was assessed by immunohistochemical staining. Results: p53 protein expression was detected in 112 (46%) of 241 NSCLC cases included in this study. p53 expression was independently associated with the presence of necrosis (odds ratio [OR], 2.316; 95% confidence interval [CI], 1.215~4.416; p=0.011). Non-adenocarcinoma histology (OR, 8.049; 95% CI, 4.072~15.911; p<0.001) and poorly differentiation (OR, 6.474; 95% CI, 2.998~13.979; p<0.001) were also independently associated with the presence of necrosis. However, p53 expression was not a significant factor for SUVmax. Conclusion: p53 protein expression is independently associated with the presence of necrosis, but not SUVmax.
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제안 방법
Pathologic stage was determined on the basis of all available data. Patients meeting the following criteria were included in this study: pathologic stage I NSCLC (excluding carcinoid, mucoepidermoid carcinoma, or adenoid cystic carcinoma) treated by lung resection surgery and mediastinal lymph node dissection or sampling; immunohistochemical staining of primary tumor for p53 expression; 18F-FDG PET/CT imaging performed within 30 days of lung cancer surgery at the Samsung Medical Center only; tumor diameter more than 1 cm due to spatial resolution of the PET scanner13; and no neoadjuvant therapy. Patients with no description of necrosis in the pathologic report were excluded.
데이터처리
Categorical variables were analyzed by Pearson's chi-square test or Fisher's exact test.
이론/모형
Immunohistochemical staining was performed using the avidin-biotinylated horseradish peroxidase complex method (DAKO LSAB kit). Briefly, 4-μm thick formalin-fixed paraffin-embedded lung tissue sections were prepared for immunohistochemistry.
Categorical variables were analyzed by Pearson's chi-square test or Fisher's exact test. The linear-by-linear association method was used to test for trends across an ordinal categorical variable. For multivariate logistic regression analysis, independent variables were selected on the basis of clinical and biological relevance with necrosis and tested for associations between necrosis and independent variables using the enter method.
성능/효과
001) compared the counterparts. After adjustment for stage, histology, grade of differentiation, and p53 expression for multiple linear regression analysis, stage IB (coefficient, 2.805; standard error [SE], 0.798; p=0.001), poorly differentiation (coefficient, 2.006; SE, 0.835; p=0.017), non-adenocarcinoma (coefficient,7.219; SE, 0.776; p＜0.001) were found to be independent variables for SUVmax. However, p53 expression was not a significant variable for SUVmax (p=0.
Multivariate logistic regression analysis adjusted for stage, histology (adenocarcinoma vs non-adenocarcinoma), grade of differentiation (well and moderately vs. poorly), and p53 expression revealed that p53 expression was independently associated with the presence of necrosis (odds ratio [OR], 2.316; 95% confidence interval [CI], 1.215∼4.416; p=0.011) (Table 4, Figure 1).
In the present study, we demonstrated that p53 expression was a significant and independent factor associated with tumor necrosis in patient with stage I NSCLC. Of note, all cases in this study had no history of chemotherapy or radiotherapy before surgical resection; therefore the presence of necrosis reflects naturally occurring cell death caused by failure to overcome various metabolic stresses during the early course of NSCLC progression. The association between necrosis and p53 expression thus provides additional indirect support for a pro-survival function of the tumor suppressor p53 in cancer.
후속연구
Because tumor p53-positivity was defined as a score ≥10% in a previous research from our institution using NSCLC tissues14, we applied the same criteria in this study. However, further study to validate the criteria is needed. To reduce bias in the interpretation of p53 expression, immunohistochemical evaluation incorporated both stain intensity and percentage such as HSCORE may be helpful in the future study26.
SUVmax on 18F-FDG PET is a semiquantitative index which might be affected by fasting duration, plasma glucose level, region of interest parameters, and cellular density of tumors21. To investigate the association between molecular markers and SUVmax, subgrouping according to histology, grade of differentiation, and stage might be necessary in the future study.
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