EGFR and KRAS Mutations in the Non-Tumoral Lung. Prognosis in Patients with Adenocarcinoma

被引:5
作者
Chalela, Roberto [1 ,2 ,3 ,4 ]
Bellosillo, Beatriz [2 ,3 ,5 ]
Curull, Victor [1 ,2 ,4 ,6 ]
Longaron, Raquel [5 ]
Pascual-Guardia, Sergi [1 ,2 ,3 ,4 ]
Badenes-Bonet, Diana [1 ,2 ,3 ]
Arriola, Edurne [2 ,7 ]
Sanchez-Font, Albert [1 ,2 ,6 ]
Pijuan, Lara [5 ]
Gea, Joaquim [1 ,2 ,3 ,4 ]
机构
[1] Hosp del Mar, Resp Med Dept, Barcelona 08003, Spain
[2] Hosp del Mar Med Res Inst IMIM, Barcelona 08003, Spain
[3] Univ Pompeu Fabra, Sch Hlth & Life Sci, Barcelona 08003, Spain
[4] Inst Salud Carlos III, CIBER Enfermedades Resp CibeRes, Madrid 28029, Spain
[5] Hosp del Mar, Dept Pathol, Barcelona 08003, Spain
[6] Univ Autonoma Barcelona, Barcelona 08003, Spain
[7] Hosp del Mar, Dept Oncol, Barcelona 08003, Spain
关键词
Adenocarcinoma; Mutations; EGFR; KRAS; Prognosis; CANCER; SURVIVAL; CLASSIFICATION; ASSOCIATION;
D O I
10.3390/jcm8040529
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Tumor recurrence is frequent and survival rates remain extremely low in lung adenocarcinoma (ADC). We hypothesize that carcinogenic factors will promote loco-regional modifications not only in the future tumor, but throughout the exposed lung. Objective: To analyze whether the most prevalent mutations observed in ADC can also be observed in the non-neoplastic lung tissue, as well as the short-term prognosis implications of this finding. Methods: Non-tumoral lung parenchyma specimens obtained during surgery from 47 patients with EGFR and/or KRAS abnormalities in their ADC tumors underwent similar genomic testing. Short-term outcomes were also recorded. Results: The same mutations were present in the tumor and the histologically normal tissue in 21.3% of patients (SM group). Although local recurrences were similar in both groups, distant metastases were more frequent in the former (60 vs. 5.4%, p < 0.001). Moreover, SM patients showed lower time-to-progression (8.5 vs. 11.7 months, p < 0.001) and disease-free survival (8.5 vs. 11.2 months, p < 0.001). COX regression showed a higher risk of progression or death (DFS) in the SM group (HR 5.94, p < 0.01]. Similar results were observed when adjusting for potential confounding variables. Conclusions: These results confirm that genetic changes are present in the apparently normal lung in many ADC patients, and this finding has prognostic implications.
引用
收藏
页数:12
相关论文
共 31 条
[1]   Cancer-Associated Mutations in Endometriosis without Cancer [J].
Anglesio, M. S. ;
Papadopoulos, N. ;
Ayhan, A. ;
Nazeran, T. M. ;
Noe, M. ;
Horlings, H. M. ;
Lum, A. ;
Jones, S. ;
Senz, J. ;
Seckin, T. ;
Ho, J. ;
Wu, R. -C. ;
Lac, V. ;
Ogawa, H. ;
Tessier-Cloutier, B. ;
Alhassan, R. ;
Wang, A. ;
Wang, Y. ;
Cohen, J. D. ;
Wong, F. ;
Hasanovic, A. ;
Orr, N. ;
Zhang, M. ;
Popoli, M. ;
McMahon, W. ;
Wood, L. D. ;
Mattox, A. ;
Allaire, C. ;
Segars, J. ;
Williams, C. ;
Tomasetti, C. ;
Boyd, N. ;
Kinzler, K. W. ;
Gilks, C. B. ;
Diaz, L. ;
Wang, T. -L. ;
Vogelstein, B. ;
Yong, P. J. ;
Huntsman, D. G. ;
Shih, I. -M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (19) :1835-1848
[2]  
[Anonymous], 2016, American college health association-national college health assessment II: Ontario Canada reference group executive summary Spring 2016, P1
[3]   Optimizing the Detection of Lung Cancer Patients Harboring Anaplastic Lymphoma Kinase (ALK) Gene Rearrangements Potentially Suitable for ALK Inhibitor Treatment [J].
Camidge, D. Ross ;
Kono, Scott A. ;
Flacco, Antonella ;
Tan, Aik-Choon ;
Doebele, Robert C. ;
Zhou, Qing ;
Crino, Lucio ;
Franklin, Wilbur A. ;
Varella-Garcia, Marileila .
CLINICAL CANCER RESEARCH, 2010, 16 (22) :5581-5590
[4]   2011: the immune hallmarks of cancer [J].
Cavallo, Federica ;
De Giovanni, Carla ;
Nanni, Patrizia ;
Forni, Guido ;
Lollini, Pier-Luigi .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2011, 60 (03) :319-326
[5]   Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy [J].
Chalela, Roberto ;
Curull, Victor ;
Enriquez, Cesar ;
Pijuan, Lara ;
Bellosillo, Beatriz ;
Gea, Joaquim .
JOURNAL OF THORACIC DISEASE, 2017, 9 (07) :2142-2158
[6]   Comprehensive molecular profiling of lung adenocarcinoma [J].
Collisson, Eric A. ;
Campbell, Joshua D. ;
Brooks, Angela N. ;
Berger, Alice H. ;
Lee, William ;
Chmielecki, Juliann ;
Beer, David G. ;
Cope, Leslie ;
Creighton, Chad J. ;
Danilova, Ludmila ;
Ding, Li ;
Getz, Gad ;
Hammerman, Peter S. ;
Hayes, D. Neil ;
Hernandez, Bryan ;
Herman, James G. ;
Heymach, John V. ;
Jurisica, Igor ;
Kucherlapati, Raju ;
Kwiatkowski, David ;
Ladanyi, Marc ;
Robertson, Gordon ;
Schultz, Nikolaus ;
Shen, Ronglai ;
Sinha, Rileen ;
Sougnez, Carrie ;
Tsao, Ming-Sound ;
Travis, William D. ;
Weinstein, John N. ;
Wigle, Dennis A. ;
Wilkerson, Matthew D. ;
Chu, Andy ;
Cherniack, Andrew D. ;
Hadjipanayis, Angela ;
Rosenberg, Mara ;
Weisenberger, Daniel J. ;
Laird, Peter W. ;
Radenbaugh, Amie ;
Ma, Singer ;
Stuart, Joshua M. ;
Byers, Lauren Averett ;
Baylin, Stephen B. ;
Govindan, Ramaswamy ;
Meyerson, Matthew ;
Rosenberg, Mara ;
Gabriel, Stacey B. ;
Cibulskis, Kristian ;
Sougnez, Carrie ;
Kim, Jaegil ;
Stewart, Chip .
NATURE, 2014, 511 (7511) :543-550
[7]   Somatic alterations in lung cancer: Do environmental factors matter? [J].
Gibelin, Cecilia ;
Couraud, Sebastien .
LUNG CANCER, 2016, 100 :45-52
[8]   The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer [J].
Goldstraw, Peter ;
Chansky, Kari ;
Crowley, John ;
Rami-Porta, Ramon ;
Asamura, Hisao ;
Eberhardt, Wilfried E. E. ;
Nicholson, Andrew G. ;
Groome, Patti ;
Mitchell, Alan ;
Bolejack, Vanessa .
JOURNAL OF THORACIC ONCOLOGY, 2016, 11 (01) :39-51
[9]   Lung cancer: current therapies and new targeted treatments [J].
Hirsch, Fred R. ;
Scagliotti, Giorgio V. ;
Mulshine, James L. ;
Kwon, Regina ;
Curran, Walter J. ;
Wu, Yi-Long ;
Paz-Ares, Luis .
LANCET, 2017, 389 (10066) :299-311
[10]   KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma [J].
Kadota, Kyuichi ;
Sima, Camelia S. ;
Arcila, Maria E. ;
Hedvat, Cyrus ;
Kris, Mark G. ;
Jones, David R. ;
Adusumilli, Prasad S. ;
Travis, William D. .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2016, 40 (12) :1579-1590