Malignant Pleural Effusion Supernatants Are Substitutes for Metastatic Pleural Tumor Tissues in EGFR Mutation Test in Patients with Advanced Lung Adenocarcinoma
Background Though the possibility of using malignant pleural effusions (MPEs) as alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth factor receptor (EGFR) mutation test has been examined, due to the lack of studies comparing the results in matching MPEs and MPTTs, the clinical value of MPEs for advanced adenocarcinoma patients with pleural effusions is not confirmed. Methods EGFR mutation statuses in matching MPTTs, MPE supernatants and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by thoracoscopy were analyzed using amplification refractory mutation system (ARMS). Results EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis. Generally, the same EGFR statuses were identified in both MPTTs and matching MPE cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19), specificity was 90.9% (20/22). Conclusions The high concordance of EGFR mutation statuses between MPEs and MPTTs in lung adenocarcinoma patients with pleural metastasis as determined by ARMS analysis suggests that MPEs, particularly MPE supernatants, may be substitutes for MPTTs in EGFR mutation test.
References
[1]
Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60: 277–300. doi: 10.3322/caac.20073
[2]
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, et al. (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127: 2893–2917. doi: 10.1002/ijc.25516
[3]
Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, et al. (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350: 2129–2139. doi: 10.1056/nejmoa040938
[4]
Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, et al. (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304: 1497–1500. doi: 10.1126/science.1099314
[5]
Yatabe Y, Hida T, Horio Y, Kosaka T, Takahashi T, et al. (2006) A rapid, sensitive assay to detect EGFR mutation in small biopsy specimens from lung cancer. J Mol Diagn 8: 335–341. doi: 10.2353/jmoldx.2006.050104
[6]
Do H, Krypuy M, Mitchell PL, Fox SB, Dobrovic A (2008) High resolution melting analysis for rapid and sensitive EGFR and KRAS mutation detection in formalin fixed paraffin embedded biopsies. BMC Cancer 8: 142. doi: 10.1186/1471-2407-8-142
[7]
Kawada I, Soejima K, Watanabe H, Nakachi I, Yasuda H, et al. (2008) An alternative method for screening EGFR mutation using RFLP in non-small cell lung cancer patients. J Thorac Oncol 3: 1096–1103. doi: 10.1097/jto.0b013e318186fadd
[8]
Jian G, Songwen Z, Ling Z, Qinfang D, Jie Z, et al. (2010) Prediction of epidermal growth factor receptor mutations in the plasma/pleural effusion to efficacy of gefitinib treatment in advanced non-small cell lung cancer. J Cancer Res Clin Oncol 136: 1341–1347. doi: 10.1007/s00432-010-0785-z
[9]
Soh J, Toyooka S, Aoe K, Asano H, Ichihara S, et al. (2006) Usefulness of EGFR mutation screening in pleural fluid to predict the clinical outcome of gefitinib treated patients with lung cancer. Int J Cancer 119: 2353–2358. doi: 10.1002/ijc.22190
[10]
Kimura H, Fujiwara Y, Sone T, Kunitoh H, Tamura T, et al. (2006) EGFR mutation status in tumour-derived DNA from pleural effusion fluid is a practical basis for predicting the response to gefitinib. Br J Cancer 95: 1390–1395.
[11]
Kimura H, Fujiwara Y, Sone T, Kunitoh H, Tamura T, et al. (2006) High sensitivity detection of epidermal growth factor receptor mutations in the pleural effusion of non-small cell lung cancer patients. Cancer Sci 97: 642–648. doi: 10.1111/j.1349-7006.2006.00216.x
[12]
Wu SG, Gow CH, Yu CJ, Chang YL, Yang CH, et al. (2008) Frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of lung adenocarcinoma. Eur Respir J 32: 924–930. doi: 10.1183/09031936.00167407
[13]
Viera AJ, Garrett JM (2005) Understanding interobserver agreement: the kappa statistic. Fam Med 37: 360–363.
[14]
Schiller JH (2001) Current standards of care in small-cell and non-small-cell lung cancer. Oncology 61 Suppl 13–13. doi: 10.1159/000055386
[15]
Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7: 169–181. doi: 10.1038/nrc2088
[16]
Jiang SX, Yamashita K, Yamamoto M, Piao CJ, Umezawa A, et al. (2008) EGFR genetic heterogeneity of nonsmall cell lung cancers contributing to acquired gefitinib resistance. Int J Cancer 123: 2480–2486. doi: 10.1002/ijc.23868
[17]
Canto A, Ferrer G, Romagosa V, Moya J, Bernat R (1985) Lung cancer and pleural effusion. Clinical significance and study of pleural metastatic locations. Chest 87: 649–652. doi: 10.1378/chest.87.5.649
[18]
Sekine I, Sumi M, Saijo N (2008) Local control of regional and metastatic lesions and indication for systemic chemotherapy in patients with non-small cell lung cancer. Oncologist 13 Suppl 121–27. doi: 10.1634/theoncologist.13-s1-21
[19]
Hung MS, Lin CK, Leu SW, Wu MY, Tsai YH, et al. (2006) Epidermal growth factor receptor mutations in cells from non-small cell lung cancer malignant pleural effusions. Chang Gung Med J 29: 373–379.
[20]
Zhang X, Zhao Y, Wang M, Yap WS, Chang AY (2008) Detection and comparison of epidermal growth factor receptor mutations in cells and fluid of malignant pleural effusion in non-small cell lung cancer. Lung Cancer 60: 175–182. doi: 10.1016/j.lungcan.2007.10.011
[21]
Taniguchi K, Okami J, Kodama K, Higashiyama M, Kato K (2008) Intratumor heterogeneity of epidermal growth factor receptor mutations in lung cancer and its correlation to the response to gefitinib. Cancer Sci 99: 929–935. doi: 10.1111/j.1349-7006.2008.00782.x
[22]
Nakano H, Soda H, Takasu M, Tomonaga N, Yamaguchi H, et al. (2008) Heterogeneity of epidermal growth factor receptor mutations within a mixed adenocarcinoma lung nodule. Lung Cancer 60: 136–140. doi: 10.1016/j.lungcan.2007.08.021