Fibroblast growth factor receptor 1 gene amplification and protein expression in human lung cancer

Cancer Medicine - Tập 9 Số 10 - Trang 3574-3583 - 2020
Omar Elakad1, Anna‐Maria Lois1, Katja Schmitz1, Sha Yao1, Sara Hugo1, Laura Lukat1, Marc Hinterthaner2, Bernhard C. Danner2, Alexander von Hammerstein‐Equord2, Kirsten Reuter‐Jessen1, Hans‐Ulrich Schildhaus1, Philipp Ströbel1, Hanibal Bohnenberger1
1Institute of Pathology, University Medical Center, Göttingen, Germany
2Department of Thoracic and Cardiovascular Surgery, University Medical Center, Göttingen, Germany

Tóm tắt

AbstractBackgroundTargeting fibroblast growth factor receptor 1 (FGFR1) is a potential treatment for squamous cell lung cancer (SQCLC). So far, treatment decision in clinical studies is based on gene amplification. However, only a minority of patients have shown durable response. Furthermore, former studies have revealed contrasting results regarding the impact of FGFR1 amplification and expression on patient's prognosis.AimsHere, we analyzed prevalence and correlation of FGFR1 gene amplification and protein expression in human lung cancer and their impact on overall survival.Materials & MethodsFGFR1 gene amplification and protein expression were analyzed by fluorescence in situ hybridization and immunohistochemistry (IHC) in 208 SQCLC and 45 small cell lung cancers (SCLC). Furthermore, FGFR1 protein expression was analyzed in 121 pulmonary adenocarcinomas (ACs). Amplification and expression were correlated to each other, clinicopathological characteristics, and overall survival.ResultsFGFR1 was amplified in 23% of SQCLC and 8% of SCLC. Amplification was correlated to males (P = .027) but not to overall survival. Specificity of immunostaining was verified by cellular CRISPR/Cas9 FGFR1 knockout. FGFR1 was strongly expressed in 9% of SQCLC, 35% of AC, and 4% of SCLC. Expression was correlated to females (P = .0187) and to the absence of lymph node metastasis in SQCLC (P = .018) with no significant correlation to overall survival. Interestingly, no significant correlation between amplification and expression was detected.DiscussionFGFR1 gene amplification does not seem to correlate to protein expression.ConclusionWe believe that patient selection for FGFR1 inhibitors in clinical studies should be reconsidered. Neither FGFR1 amplification nor expression influences patient's prognosis.

Từ khóa


Tài liệu tham khảo

10.3322/caac.21492

10.1097/JTO.0b013e31826aed28

10.1038/nature25183

10.21037/tlcr.2016.06.07

10.1056/NEJMoa040938

10.1038/nature05945

10.1158/1078-0432.CCR-17-0478

10.1080/15384101.2015.1041691

10.1093/annonc/mdt419

10.18632/oncotarget.14109

10.1111/cas.13071

10.1182/blood-2013-03-489823

10.18632/oncotarget.12198

10.1016/j.jtho.2015.08.003

10.1186/s12957-016-1081-4

10.1158/1078-0432.CCR-14-2329

10.1126/scitranslmed.3001451

10.1038/modpathol.2013.141

10.1038/cddiscovery.2015.49

10.1155/2015/763080

10.1038/bjc.2014.229

10.1002/cjp2.51

Yang W, 2014, Prognostic value of FGFR1 gene copy number in patients with non‐small cell lung cancer: a meta‐analysis, J Thorac Dis, 6, 803

10.1158/1078-0432.CCR-17-0645

10.1200/JCO.2016.67.2048

10.1038/modpathol.2012.102

10.1038/modpathol.2014.71

10.1021/acs.jproteome.6b00403

Varsegi GM, 2009, Cell block preparation from cytology specimen with predominance of individually scattered cells, J Vis Exp, 29, e1316

10.15252/emmm.201708428

10.1158/1078-0432.CCR-08-0167

10.1097/JTO.0000000000000562

10.1186/s13059-014-0560-6

10.1126/science.1260419

10.1124/mol.108.049544

10.1371/journal.pone.0020351

10.1371/journal.pone.0149628

10.1007/s00428-014-1634-2

10.1093/ajcp/aqv013

10.18632/oncotarget.19279

10.1007/s00428-012-1250-y

Yang F, 2013, Elevated expression of SOX2 and FGFR1 in correlation with poor prognosis in patients with small cell lung cancer, Int J Clin Exp Pathol, 6, 2846

Sasaki H, 2012, Increased FGFR1 copy number in lung squamous cell carcinomas, Mol Med Rep, 5, 725

10.1016/j.jtho.2019.05.041

10.1309/VACP-VLQA-G9DX-VUDF

10.1002/ijc.27997

Massenhausen A, 2013, FGFR1 as a novel prognostic and predictive biomarker in squamous cell cancers of the lung and the head and neck area, Ann Transl Med, 1, 23

10.1002/ijc.28090

Thông tin
Thông tin xuất bản

Cancer Medicine

Tập 9 Số 10

3574-3583

Thông tin tác giả