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Thyroid transcription factor 1 and p63 expression is associated with survival outcome in patients with non-small cell lung cancer treated with erlotinib

. 2020 Aug ; 20 (2) : 1376-1382. [epub] 20200521

Status PubMed-not-MEDLINE Language English Country Greece Media print-electronic

Document type Journal Article

While erlotinib is primarily administered to patients with non-small cell lung cancer with sensitizing epidermal growth factor receptor (EGFR) mutations, it is also prescribed to patients with wild type (wt) EGFR in higher lines of treatment. However, there is no predictive marker for erlotinib efficacy in patients with EGFR wt. Certain immunohistochemical (IHC) parameters, including thyroid transcription factor 1 (TTF1) and p63, have been reported to indicate predictive power in patients with EGFR wt. The present study focused on retrospective data from the University Hospital in Pilsen using the TULUNG register. TTF1 and p63 expression data were extracted from the hospital information system and merged with registry data to calculate progression-free survival (PFS) and overall survival (OS) rates. A cohort of 345 patients with adenocarcinoma (ADC) or squamous cell carcinoma (SCC) exhibited similar erlotinib efficacies when TTF1 and p63 were ignored. However, significant differences were reported in PFS and OS rates of a subgroup of 126 patients where TTF1 and p63 parameters were known. In a univariate analysis, group A (ADC TTF1+/p63-) achieved PFS of 2.6 months, group B (SSC TTF1-/p63+) 1.9 months and group C (did not fit into groups A or B, i.e., ADC TTF1-/p63+ or SCC TTF1+/p63-) 1.4 months (P=0.006). Median OS was 14.2, 19.1 and 5.3 months for A, B and C, respectively (P=0.002). Furthermore, a multivariate analysis demonstrated IHC markers to be the only significant parameters for PFS and OS. Group C had a negative prognostic factor for PFS [hazard ratio (HR), 1.812; P=0.02] and OS (HR=2.367; P=0.01). In conclusion, patients with EGFR wt and lung carcinomas without TTF1 and p63 expression typical for ADC (TTF1+/p633-) or SCC (TTF1-/p63+) do not appear to be suitable candidates for erlotinib treatment.

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Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107. PubMed DOI

Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–781. doi: 10.1016/j.ejca.2009.12.014. PubMed DOI

Brambilla E, Travis WD, Colby TV, Corrin B, Shimosato Y. The new World Health Organization classification of lung tumours. Eur Respir J. 2001;18:1059–1068. doi: 10.1183/09031936.01.00275301. PubMed DOI

Steins M, Thomas M, Geißler M. Erlotinib. Recent Results Cancer Res. 2018;211:1–17. doi: 10.1007/978-3-319-91442-8_1. PubMed DOI

Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, et al. Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–246. doi: 10.1016/S1470-2045(11)70393-X. PubMed DOI

Tagliamento M, Genova C, Rijavec E, Rossi G, Biello F, Dal Bello MG, Alama A, Coco S, Boccardo S, Grossi F. Afatinib and Erlotinib in the treatment of squamous-cell lung cancer. Expert Opin Pharmacother. 2018;19:2055–2062. doi: 10.1080/14656566.2018.1540591. PubMed DOI

Garassino MC, Kawaguchi T, Gregorc V, Rulli E, Ando M, Marsoni S, Isa SI, Novello S, Farina G, Barni S, et al. Chemotherapy versus erlotinib as second-line treatment in patients with advanced non-small cell lung cancer and wild-type epidermal growth factor receptor: An individual patient data (IPD) analysis. ESMO Open. 2018;3:e000327. doi: 10.1136/esmoopen-2018-000327. PubMed DOI PMC

Nakahara Y, Hosomi Y, Saito M, Ogawa M, Hishima T, Okamura T, Sasaki J, Masuda N. Predictive significance of thyroid transcription factor-1 expression in patients with non-squamous non-small cell lung cancer with wild-type epidermal growth factor receptor treated with erlotinib. Mol Clin Oncol. 2016;5:14–18. doi: 10.3892/mco.2016.870. PubMed DOI PMC

Hosny Mohammed K, Ewaz A, Cohen C, Siddiqui MT. Double staining: Diagnostic utility in non-small cell lung carcinoma in the era of tissue conservation. J Am Soc Cytopathol. 2017;6:170–175. doi: 10.1016/j.jasc.2017.05.003. PubMed DOI

Sun JM, Han J, Ahn JS, Park K, Ahn MJ. Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy. J Thorac Oncol. 2011;6:1392–1399. doi: 10.1097/JTO.0b013e3182208ea8. PubMed DOI

Puglisi F, Barbone F, Damante G, Bruckbauer M, Di Lauro V, Beltrami CA, Di Loreto C. Prognostic value of thyroid transcription factor-1 in primary, resected, non-small cell lung carcinoma. Mod Pathol. 1999;12:318–324. PubMed

Elsamany SA, Al-Fayea TM, Alzahrani AS, Abozeed WN, Darwish W, Farooq MU, Almadani AS, Bukhari EA. Thyroid transcription factor-1 expression in advanced non- small cell lung cancer: Impact on survival outcome. Asian Pac J Cancer Prev. 2015;16:2987–2991. doi: 10.7314/APJCP.2015.16.7.2987. PubMed DOI

Berghmans T, Paesmans M, Mascaux C, Martin B, Meert AP, Haller A, Lafitte JJ, Sculier JP. Thyroid transcription factor 1 - a new prognostic factor in lung cancer: A meta-analysis. Ann Oncol. 2006;17:1673–1676. doi: 10.1093/annonc/mdl287. PubMed DOI

Kim JH, Kim HS, Kim BJ, Han B, Choi DR, Kwon JH. Prognostic impact of TTF-1 expression in non-squamous non-small-cell lung cancer: A meta-analysis. J Cancer. 2018;9:4279–4286. doi: 10.7150/jca.24980. PubMed DOI PMC

Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dötsch V, Andrews NC, Caput D, McKeon F. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell. 1998;2:305–316. doi: 10.1016/S1097-2765(00)80275-0. PubMed DOI

Ma Y, Fan M, Dai L, Kang X, Liu Y, Sun Y, Xiong H, Liang Z, Yan W, Chen K. Expression of p63 and CK5/6 in early-stage lung squamous cell carcinoma is not only an early diagnostic indicator but also correlates with a good prognosis. Thorac Cancer. 2015;6:288–295. doi: 10.1111/1759-7714.12181. PubMed DOI PMC

Pelosi G, Pasini F, Olsen Stenholm C, Pastorino U, Maisonneuve P, Sonzogni A, Maffini F, Pruneri G, Fraggetta F, Cavallon A, et al. p63 immunoreactivity in lung cancer: Yet another player in the development of squamous cell carcinomas? J Pathol. 2002;198:100–109. doi: 10.1002/path.1166. PubMed DOI

Matej R, Dundr P, Hornychova H, Ryska A, Ticha I. Nádory plic - doporučený postup pro bioptické vyšetření. Společnost českých patologů, 2019. http://www.patologie.info/soubory/all/2019-5_Guideline-pl%C3%ADce-web.pdf

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45:228–247. doi: 10.1016/j.ejca.2008.10.026. PubMed DOI

Reck M, van Zandwijk N, Gridelli C, Baliko Z, Rischin D, Allan S, Krzakowski M, Heigener D. Erlotinib in advanced non-small cell lung cancer: Efficacy and safety findings of the global phase IV Tarceva Lung Cancer Survival Treatment study. J Thorac Oncol. 2010;5:1616–1622. doi: 10.1097/JTO.0b013e3181f1c7b0. PubMed DOI

Germonpré P, Van den Wyngaert T. Second-line erlotinib after failure of pemetrexed-containing chemotherapy in advanced non-small cell lung cancer (NSCLC): Real-world effectiveness, safety and tolerability. PLoS One. 2019;14:e0215135. doi: 10.1371/journal.pone.0215135. PubMed DOI PMC

Hirai F, Edagawa M, Shimamatsu S, Toyozawa R, Toyokawa G, Nosaki K, Yamaguchi M, Seto T, Takenoyama M, Ichinose Y. Evaluation of erlotinib for the treatment of patients with non-small cell lung cancer with epidermal growth factor receptor wild type. Oncol Lett. 2017;14:306–312. doi: 10.3892/ol.2017.6118. PubMed DOI PMC

Zhang YL, Yuan JQ, Wang KF, Fu XH, Han XR, Threapleton D, Yang ZY, Mao C, Tang JL. The prevalence of EGFR mutation in patients with non-small cell lung cancer: A systematic review and meta-analysis. Oncotarget. 2016;7:78985–78993. doi: 10.18632/oncotarget.12587. PubMed DOI PMC

Faehling M, Eckert R, Kuom S, Kamp T, Stoiber KM, Schumann C. Benefit of erlotinib in patients with non-small-cell lung cancer is related to smoking status, gender, skin rash and radiological response but not to histology and treatment line. Oncology. 2010;78:249–258. doi: 10.1159/000315731. PubMed DOI

Yang L, Lin M, Ruan WJ, Dong LL, Chen EG, Wu XH, Ying KJ. Nkx2-1: A novel tumor biomarker of lung cancer. J Zhejiang Univ Sci B. 2012;13:855–866. doi: 10.1631/jzus.B1100382. PubMed DOI PMC

Kerr KM. Personalized medicine for lung cancer: New challenges for pathology. Histopathology. 2012;60:531–546. doi: 10.1111/j.1365-2559.2011.03854.x. PubMed DOI

Haque AK, Syed S, Lele SM, Freeman DH, Adegboyega PA. Immunohistochemical study of thyroid transcription factor-1 and HER2/neu in non-small cell lung cancer: Strong thyroid transcription factor-1 expression predicts better survival. Appl Immunohistochem Mol Morphol. 2002;10:103–109. doi: 10.1097/00129039-200206000-00002. PubMed DOI

Zhu WY, Hu XF, Fang KX, Kong QQ, Cui R, Li HF, He JY, Zhang YK, Le HB. Prognostic value of mutant p53, Ki-67, and TTF-1 and their correlation with EGFR mutation in patients with non-small cell lung cancer. Histol Histopathol. 2019;34:1269–1278. PubMed

Fiala O, Pesek M, Skrickova J, Kolek V, Salajka F, Tomiskova M, Satankova M, Kultan J, Kuliskova J, Svaton M, et al. Thyroid transcription factor 1 expression is associated with outcome of patients with non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy. Tumour Biol. 2017;39:1010428317691186. doi: 10.1177/1010428317691186. PubMed DOI

Chatziandreou I, Tsioli P, Sakellariou S, Mourkioti I, Giannopoulou I, Levidou G, Korkolopoulou P, Patsouris E, Saetta AA. Comprehensive Molecular Analysis of NSCLC; Clinicopathological Associations. PLoS One. 2015;10:e0133859. doi: 10.1371/journal.pone.0133859. PubMed DOI PMC

Zamboni M, Civitareale D. TTF-1/Nkx2.1 functional connection with mutated EGFR relies on LRIG1 and β-catenin pathways in lung cancer cells. Biochem Biophys Res Commun. 2018;505:1027–1031. doi: 10.1016/j.bbrc.2018.10.015. PubMed DOI

Phelps CA, Lai SC, Mu D. Roles of Thyroid Transcription Factor 1 in Lung Cancer Biology. Vitam Horm. 2018;106:517–544. doi: 10.1016/bs.vh.2017.05.007. PubMed DOI PMC

34. Yoh K, Prywes R. Pathway Regulation of p63, a Director of Epithelial Cell Fate. Front Endocrinol (Lausanne) 2015;6:51. PubMed PMC

Holcakova J, Nekulova M, Orzol P, Nenutil R, Podhorec J, Svoboda M, Dvorakova P, Pjechova M, Hernychova L, Vojtesek B, et al. ΔNp63 activates EGFR signaling to induce loss of adhesion in triple-negative basal-like breast cancer cells. Breast Cancer Res Treat. 2017;163:475–484. doi: 10.1007/s10549-017-4216-6. PubMed DOI

Patel TS, Shah MG, Gandhi JS, Patel P. Accuracy of cytology in sub typing non small cell lung carcinomas. Diagn Cytopathol. 2017;45:598–603. doi: 10.1002/dc.23730. PubMed DOI

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