Micropapillary Lung Adenocarcinoma EGFR, K-ras, and BRAF Mutational Profile

被引:76
作者
Achcar, Rosane De Oliveira Duarte [1 ]
Nikiforova, Marina N. [1 ]
Yousem, Samuel A. [1 ]
机构
[1] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15213 USA
关键词
Micropapillary adenocarcinoma; Papillary adenocarcinoma; Bronchioloalveolar adenocarcinoma; GROWTH-FACTOR RECEPTOR; DISTINCT PATHOLOGICAL MARKER; PROGNOSTIC-SIGNIFICANCE; HISTOLOGIC SUBTYPE; BRONCHIOLOALVEOLAR; GEFITINIB; PATTERN; SENSITIVITY; PAPILLARY; CANCER;
D O I
10.1309/AJCPBS85VJEOBPDO
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Micropapillary lung adenocarcinoma (MPA) has been reported as an aggressive variant of adenocarcinoma, frequently manifesting at high stage with a poor prognosis. We analyzed the clinical and molecular profile of 15 primary MPAs for K-ras, EGFR, and BRAF mutations and performed,fluorescence in situ hybridization for EGFR amplification. In our study, 11 (73%) of 75 MPAs harbored mutually exclusive mutations: 5 (33%) K-ras, 3 (20%) EGFR, and 3 (20%) BRA F. Mutations in all 3 genes occurred inpatients with a smoking history and tumors with mucinous differentiation and secondary lepidic, acinar, and solid growth, suggesting that in a Western population, cytomorphologic correlation with genetic mutations is more unpredictable than in Japanese cohorts. We conclude that K-ras, EGFR, and BRAF mutations are disproportionately seen in adenocarcinomas of lung with a dominant micropapillary growth pattern compared with conventional adenocarcinoma in our institutional experience.
引用
收藏
页码:694 / 700
页数:7
相关论文
共 31 条
[1]   Prognostic analysis of pulmonary adenocarcinoma subclassification with special consideration of papillary and bronchioloalveolar types [J].
Aida, S ;
Shimazaki, H ;
Sato, K ;
Sato, M ;
Deguchi, H ;
Ozeki, Y ;
Tamai, S .
HISTOPATHOLOGY, 2004, 45 (05) :468-476
[2]   Micropapillary component in lung adenocarcinoma -: A distinctive histologic feature with possible prognostic significance [J].
Amin, MB ;
Tamboli, P ;
Merchant, SH ;
Ordóñez, NG ;
Ro, J ;
Ayala, AG ;
Ro, JY .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2002, 26 (03) :358-364
[3]   Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer [J].
Cappuzzo, F ;
Hirsch, FR ;
Rossi, E ;
Bartolini, S ;
Ceresoli, GL ;
Bemis, L ;
Haney, J ;
Witta, S ;
Danenberg, K ;
Domenichini, I ;
Ludovini, V ;
Magrini, E ;
Gregorc, V ;
Doglioni, C ;
Sidoni, A ;
Tonato, M ;
Franklin, WA ;
Crino, L ;
Bunn, PA ;
Varella-Garcia, M .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2005, 97 (09) :643-655
[4]   Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer [J].
Chou, TY ;
Chiu, CH ;
Li, LH ;
Hsiao, CY ;
Tzen, CY ;
Chang, KT ;
Chen, YM ;
Perng, RP ;
Tsai, SF ;
Tsai, CM .
CLINICAL CANCER RESEARCH, 2005, 11 (10) :3750-3757
[5]   New insight into BRAF mutations in cancer [J].
Dhomen, Nathalie ;
Marais, Richard .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2007, 17 (01) :31-39
[6]   Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib [J].
Eberhard, DA ;
Johnson, BE ;
Amler, LC ;
Goddard, AD ;
Heldens, SL ;
Herbst, RS ;
Ince, WL ;
Jänne, PA ;
Januario, T ;
Johnson, DH ;
Klein, P ;
Miller, VA ;
Ostland, MA ;
Ramies, DA ;
Sebisanovic, D ;
Stinson, JA ;
Zhang, YR ;
Seshagiri, S ;
Hillan, KJ .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (25) :5900-5909
[7]   Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib [J].
Jackman, David M. ;
Yeap, Beow Y. ;
Sequist, Lecia V. ;
Lindeman, Neal ;
Holmes, Alison J. ;
Joshi, Victoria A. ;
Bell, Daphne W. ;
Huberman, Mark S. ;
Halmos, Balazs ;
Rabin, Michael S. ;
Haber, Daniel A. ;
Lynch, Thomas J. ;
Meyerson, Matthew ;
Johnson, Bruce E. ;
Jaenne, Pasi A. .
CLINICAL CANCER RESEARCH, 2006, 12 (13) :3908-3914
[8]   Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma [J].
Kamiya, Kazunori ;
Hayashi, Yuichiro ;
Douguchi, Junya ;
Hashiguchi, Akinori ;
Yamada, Taketo ;
Izumi, Yotaro ;
Watanabe, Masazumi ;
Kawamura, Masafumi ;
Horinouchi, Hirohisa ;
Shimada, Naoki ;
Kobayashi, Koichi ;
Sakamoto, Michiie .
MODERN PATHOLOGY, 2008, 21 (08) :992-1001
[9]   Micropapillary pattern and grade of stromal invasion in pT1 adenocarcinoma of the lung: usefulness as prognostic factors [J].
Kawakami, Takehito ;
Nabeshima, Kazuki ;
Makimoto, Yoshifumi ;
Hamasaki, Makoto ;
Iwasaki, Akinori ;
Shirakusa, Takayuki ;
Iwasaki, Hiroshi .
MODERN PATHOLOGY, 2007, 20 (05) :514-521
[10]   Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib [J].
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 .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (21) :2129-2139