Correlation of survival and EGFR mutation with predominant histologic subtype according to the new lung adenocarcinoma classification in stage IB patients

World Journal of Surgical Oncology

Lei Shi¹  Jun Zhao¹  Wei Hong¹  Xun Shi¹  Xinmin Yu¹  Yan Sun¹ 

[1] Department of Medical Oncology, Zhejiang Cancer Hospital, 38 Guangji road, Gongshu District, Hangzhou 310022, People’s Republic of China

关键词: EGFR mutation;    Prognosis;    Stage IB;    IASLC/ATS/ERS classification;    Lung adenocarcinoma;   

Others  :  811713
DOI  :  10.1186/1477-7819-12-148

 received in 2013-10-12, accepted in 2014-05-04,  发布年份 2014

【 摘 要 】

Background

A new lung adenocarcinoma classification proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) has recently been published. This study aimed to investigate the utility of the new histological classification for identifying the prognostic subtypes of adenocarcinomas in stage IB patients.Correlations between the classification and the presence of epidermal growth factor receptor (EGFR) mutation status was also studied.

Methods

One hundred and thirty-six patients with stage IB lung adenocarcinoma operated on in Zhejiang Cancer Hospital were identified between 2002 and 2011. Patients overall survival and disease-free survival were calculated using Kaplan-Meier and Cox regression analyses. EGFR mutations were detected using the amplification refractory mutation system.

Results

A total of 136 cases were included in current study, of which 38 were papillary predominant, 39 were acinar predominant, 22 were micropapillary predominant, 21 were lepidic predominant subtypes, 14 were solid predominant, and 2 were variants of invasive adenocarcinoma. Patients with micropapillary- and solid-predominant tumors had the lowest five-year disease-free survival (28.4 and 36.7%, respectively). Univariate and multivariate analysis showed that the micropapillary-predominant subtype was an independent predictor of disease-free survival (P = 0.0041 and 0.048, respectively), but not overall survival (P = 0.175 and 0.214, respectively). EGFR mutations were significantly associated with the micropapillary-predominant subtype patients (P = 0.0026). The EGFR mutation frequency is lower in the solid-predominant subtype than other subtypes (P = 0.0508).

Conclusions

The predominant subtype in the primary tumor was associated with prognosis in resected stage IB lung adenocarcinoma. The EGFR mutation frequency of micropapillary-predominant subtype is higher than other subtypes.

【 授权许可】

   
2014 Sun et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin 2013, 63:11-30.
• [2]Li Z, Yu Y, Lu J, Luo Q, Wu C, Liao M, Zheng Y, Ai X, Gu L, Lu S: Analysis of the T descriptors and other prognosis factors in pathologic stage I non-small cell lung cancer in China. J ThoracOncol 2009, 4:702-709.
• [3]Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, et al.: The new IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification. J Thoracic Oncol 2011, 6:244-285.
• [4]Woo T, Okudela K, Mitsui H, Tajiri M, Yamamoto T, Rino Y, Ohashi K, Masuda M: Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases. PatholInt 2012, 62:785-791.
• [5]Gu J, Lu C, Guo J, Chen L, Chu Y, Ji Y, Ge D: Prognostic significance of the IASLC/ATS/ERS classification in Chinese patients-A single institution retrospective study of 292 lung adenocarcinoma. J SurgOncol 2013, 107:474-480.
• [6]Russell PA, Barnett SA, Walkiewicz M, Wainer Z, Conron M, Wright GM, Gooi J, Knight S, Wynne R, Liew D, John T: Correlation of mutation status and survival with predominant histologic subtype according to the new IASLC/ATS/ERS lung adenocarcinoma classification in stage III (N2) patients. J ThoracOncol 2013, 8:461-468.
• [7]Yoshizawa A, Motoi N, Riely GJ, Sima CS, Gerald WL, Kris MG, Park BJ, Rusch VW, Travis WD: Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases. Mod Pathol 2011, 24:653-664.
• [8]Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M: Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010, 11:121-128.
• [9]Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010, 362:2380-2388.
• [10]Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L: Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005, 353:123-132.
• [11]Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009, 361:947-957.
• [12]Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004, 350:2129-2139.
• [13]Yoshizawa A, Sumiyoshi S, Sonobe M, Kobayashi M, Fujimoto M, Kawakami F, Tsuruyama T, Travis WD, Date H, Haga H: Validation of the IASLC/ATS/ERS lung adenocarcinoma classification for prognosis and association with EGFR and KRAS gene mutations: analysis of 440 Japanese patients. J ThoracOncol 2013, 8:52-61.
• [14]Hung JJ, Jeng WJ, Chou TY, Hsu WH, Wu KJ, Huang BS, Wu YC: Prognostic value of the New international association for the study of lung cancer/American thoracic society/European respiratory society lung adenocarcinoma classification on death and recurrence in completely resected stage I lung adenocarcinoma. Ann Surg 2013, 258:1079-1086.
• [15]Song Z, Zhu H, Guo Z, Sun W, Zhang Y: Prognostic value of the IASLC/ATS/ERS classification in stage I lung adenocarcinoma patients-based on a hospital study in China. Eur J SurgOncol 2013, 39:1262-1268.
• [16]Shim HS, da Lee H, Park EJ, Kim SH: Histopathologic characteristics of lung adenocarcinomas with epidermal growth factor receptor mutations in the international association for the study of lung cancer/American thoracic society/European respiratory society lung adenocarcinoma classification. Arch Pathol Lab Med 2011, 135:1329-1334.
• [17]Zhang Y, Sun Y, Pan Y, Li C, Shen L, Li Y, Luo X, Ye T, Wang R, Hu H, Li H, Wang L, Pao W, Chen H: Frequency of driver mutations in lung adenocarcinoma from female never-smokers varies with histologic subtypes and age at diagnosis. Clin Cancer Res 2012, 18:1947-1953.
• [18]Song Z, Zhu H, Wu W, Sun W, Zhang Y: Correlation of EGFR mutation and predominant histologic subtype according to the new lung adenocarcinoma classification in Chinese patients. Med Oncol 2013, 30:645.