Malobuněčný karcinom plic – nové poznatky o biologii nádoru

Czech version

Authors: Klára Pavlíčková ¹; Radoslav Matěj ^1,2,3
Authors‘ workplace: Ústav patologie a molekulární medicíny 3. LF UK, Fakultní Thomayerova nemocnice, Praha ¹; Ústav patologie 3. LF UK, Fakultní nemocnice Královské Vinohrady, Praha ²; Ústav patologie 1. LF UK, Všeobecná fakultní nemocnice, Praha ³
Published in: Čes.-slov. Patol., 59, 2023, No. 1, p. 18-22
Category: Reviews Article

Overview

Small cell lung carcinoma (SCLC) is a high grade neuroendocrinne tumour accounting for approximately 15 % of lung cancers. It is characterised by early relapse and low survival rate. The treatment has remained unchanged for decades. Histological and cytological characteristics are summarised in brief, along with genetic alterations of the tumour. A new molecular subtype classification is presented according to the expression of transciptional factors ASCL1 (SCLC-A), NEUROD1 (SCLC-D), POU2F3 (SCLC-P) and YAP1 (SCLC-Y). These subtypes represent different ways of tumorigenesis, and the distinct genomic alterations may offer new therapeutic strategies.

Keywords:

small cell lung carcinoma– ASCL1 – NEUROD1 – POU2F3 – YAP1

Sources

1. Baine MK, Febres-Aldana CA, Chang JC, Jungbluth AA, Sethi S, Antonescu CR, et al. POU2F3 in SCLC: Clinicopathologic and Genomic Analysis With a Focus on Its Diagnostic Utility in Neuroendocrine-Low SCLC. J Thorac Oncol 2022; 17(9): 1109-21.

2. WHO Classification of Tumours Editorial Board Thoracic Tumours. WHO Classification of Tumours, 5th Edition, Volume 5, 2021

3. Pesch B, Kendzia B, Gustavsson P, Jockel KH, Johnen G, Pohlabeln H, et al. Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of case-control studies. Int J Cancer 2012; 131(5): 1210-1219.

4. Pešek M. Malobuněčný karcinom plic: epidemiologie, diagnostika a léčba. Vnitř Lék 2017.

5. Ganti AKP, Loo BW, Bassetti M, Blakely C, Chiang A, D’Amico TA, et al. Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19(12): 1441-1464.

6. Galanis E, Frytak S, Lloyd RV. Extrapulmonary small cell carcinoma. Cancer 1997;c 79(9): 1729-1736.

7. Svajdler M, Mezencev R, Saskova B, Ondic O, Mukensnabl P, Michal M. Triple marker composed of p16, CD56, and TTF1 shows higher sensitivity than INSM1 for diagnosis of pulmonary small cell carcinoma: proposal for a rational immunohistochemical algorithm for diagnosis of small cell carcinoma in small biopsy and cytology specimens. Hum Pathol 2019; 85: 58-64.

8. Khalbuss WE, Yang H, Lian Q, Elhosseiny A, Pantanowitz L, Monaco SE. The cytomorphologic spectrum of small-cell carcinoma and large-cell neuroendocrine carcinoma in body cavity effusions: A study of 68 cases. Cytojournal 2011; 8: 18.

9. Van Lommel A. Pulmonary neuroendocrine cells (PNEC) and neuroepithelial bodies (NEB): chemoreceptors and regulators of lung development. Paediatr Respir Rev 2001; 2(2): 171-6.

10. Nagy-Mignotte H, Shestaeva O, Vignoud L, Guillem P, Ruckly S, Chabre O, et al. Prognostic impact of paraneoplastic cushing’s syndrome in small-cell lung cancer. J Thorac Oncol 2014; 9(4): 497-505.

11. Maddison P, Gozzard P, Grainge MJ, Lang B. Long-term survival in paraneoplastic Lambert- Eaton myasthenic syndrome. Neurology 2017; 88(14): 1334-9.

12. George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, et al. Comprehensive genomic profiles of small cell lung cancer. Nature 2015; 524(7563): 47-53.

13. Jones PA, Issa JP, Baylin S. Targeting the cancer epigenome for therapy. Nat Rev Genet 2016; 17(10): 630-41.

14. Pleasance ED, Stephens PJ, O’Meara S, Mc- Bride DJ, Meynert A, Jones D, et al. A smallcell lung cancer genome with complex signatures of tobacco exposure. Nature 2010; 463(7278): 184-190.

15. Roberts SA, Lawrence MS, Klimczak LJ, Grimm SA, Fargo D, Stojanov P, et al. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet 2013; 45(9): 970-976.

16. Whang-Peng J, Kao-Shan CS, Lee EC, Bunn PA, Carney DN, Gazdar AF, et al. Specific chromosome defect associated with human small-cell lung cancer; deletion 3p(14-23). Science 1982; 215(4529): 181-182.

17. Nicholson SA, Beasley MB, Brambilla E, Hasleton PS, Colby TV, Sheppard MN, et al. Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens. Am J Surg Pathol 2002; 26(9): 1184-1197.

18. Poirier JT, Gardner EE, Connis N, Moreira AL, de Stanchina E, Hann CL, et al. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2. Oncogene 2015; 34(48): 5869-5878.

19. Borges M, Linnoila RI, van de Velde HJ, Chen H, Nelkin BD, Mabry M, et al. An achaete-scute homologue essential for neuroendocrine differentiation in the lung. Nature 1997; 386(6627): 852-855.

20. Rudin CM, Pietanza MC, Bauer TM, Ready N, Morgensztern D, Glisson BS, et al. Rovalpituzumab tesirine, a DLL3-targeted antibody- drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol 2017; 18(1): 42-51.

21. Borromeo MD, Savage TK, Kollipara RK, He M, Augustyn A, Osborne JK, et al. ASCL1 and NEUROD1 Reveal Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct Genetic Programs. Cell Rep 2016; 16(5): 1259-1272.

22. Huang YH, Klingbeil O, He XY, Wu XS, Arun G, Lu B, et al. POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer. Genes Dev 2018; 32(13-14): 915-928.

23. Owonikoko TK, Dwivedi B, Chen Z, Zhang C, Barwick B, Ernani V, et al. YAP1 Expression in SCLC Defines a Distinct Subtype With T-cell-Inflamed Phenotype. J Thorac Oncol 2021; 16(3): 464-476.

24. Qu S, Fetsch P, Thomas A, Pommier Y, Schrump DS, Miettinen MM, et al. Molecular Subtypes of Primary SCLC Tumors and Their Associations With Neuroendocrine and Therapeutic Markers. J Thorac Oncol 2022; 17(1): 141-153.

25. Byers LA, Bentsion D, Gans S, Penkov K, Son C, Sibille A, et al. Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naive Extensive-Stage Small Cell Lung Cancer: A Phase 2 Randomized Study. Clin Cancer Res 2021; 27(14): 3884- 3895.

26. Gardner EE, Lok BH, Schneeberger VE, Desmeules P, Miles LA, Arnold PK, et al. Chemosensitive Relapse in Small Cell Lung Cancer Proceeds through an EZH2-SLFN11 Axis. Cancer Cell 2017; 31(2): 286-299.

27. Sabari JK, Lok BH, Laird JH, Poirier JT, Rudin CM. Unravelling the biology of SCLC: implications for therapy. Nat Rev Clin Oncol 2017; 14(9): 549-561.

28. Arbour KC, Mezquita L, Long N, Rizvi H, Auclin E, Ni A, et al. Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer. J Clin Oncol 2018; 36(28): 2872-2878.

29. Pavan A, Attili I, Pasello G, Guarneri V, Conte PF, Bonanno L. Immunotherapy in smallcell lung cancer: from molecular promises to clinical challenges. J Immunother Cancer 2019; 7(1): 205.

30. Mohan S, Foy V, Ayub M, Leong HS, Schofield P, Sahoo S, et al. Profiling of Circulating Free DNA Using Targeted and Genome-wide Sequencing in Patients with SCLC. J Thorac Oncol 2020; 15(2): 216-230.