МОЛЕКУЛЯРНО-БИОЛОГИЧЕСКИЕ МАРКЕРЫ В ДИАГНОСТИКЕ НЕЙРОЭНДОКРИННЫХ ОПУХОЛЕЙ

DOI: https://doi.org/None

В.В. Делекторская, доктор медицинских наук Российский онкологический научный центр им. Н.Н. Блохина, Российская Федерация, 115478, Москва, Каширское шоссе, д. 24 E-mail: [email protected]

Нейроэндокринные опухоли (НЭО) образуют гетерогенную группу относительно редких новообразований, частота выявления которых значительно увеличилась в последние десятилетия. Эти опухоли развиваются из клеток с нейроэндокринным фенотипом и могут возникать в любом органе, но наиболее часто наблюдаются в гастроэнтеропанкреатической системе и легком. НЭО имеют общие характерные морфологические, иммуногистохимические, ультраструктурные и молекулярные особенности. Статья посвящена анализу современных представлений о природе НЭО и особенностях их биологического поведения. Обсуждаются вопросы последних классификаций и морфологической диагностики с учетом гистологических и иммуногистохимических критериев. Включены последние данные о диагностических маркерах и градации опухолей. Последняя основывается на подсчете количества митозов и определении пролиферативной активности с помощью индекса Ki-67. В статье также освещаются данные о ключевых молекулярных маркерах, влияющих на прогноз и лекарственную чувствительность НЭО пищеварительной и бронхопульмональной систем.
Ключевые слова: 
нейроэндокринная опухоль, диагностика, молекулярные маркеры, иммуногистохимия, респираторный тракт
Для цитирования: 
Делекторская В.В. МОЛЕКУЛЯРНО-БИОЛОГИЧЕСКИЕ МАРКЕРЫ В ДИАГНОСТИКЕ НЕЙРОЭНДОКРИННЫХ ОПУХОЛЕЙ. Молекулярная медицина, 2015; (2): -
Список литературы: 
  1. Klöppel G. Tumour biology and histopathology of neuroendocrine tumours. Best Practice Res. Clin. Endocrin Metabol. 2007; 21 (1): 15–31.
  2. Öberg K.E. Gastrointestinal neuroendocrine tumors. Ann. Oncol. 2010; 21 (Suppl. 7): 72–80.
  3. Caplin M., Yao J.C. An overview of thoracic and gastrointestinal neuroendocrine tumours. In: Caplin M., Yao J.C. (eds.). Handbook of Gastroenteropancreatic and Thoracic Neuroendocrine Tumours. BioScientifica. 2011: 1–9.
  4. Klimstra D.S., Modlin I.R., Coppola D. et al. The Pathologic Classification of Neuroendocrine Tumors. A Review of Nomenclature, Grading, and Staging Systems. Pancreas. 2010; 39 (6): 707–12.
  5. Rindi G., Bordi C. Endocrine tumours of the gastrointestinal tract: etiology, molecular pathogenesis and genetics. Best. Pract. Res. Clin. Gastroenterol. 2005; 19 (4): 519–34.
  6. Cives M., Strosberg J. An update on gastroenteropancreatic neuroendocrine tumors. oncology (Williston Park). 2014; 28 (9): pii: 201359.
  7. Yao J.C., Hassan M., Phan A. et al. One hundred years after «carcinoid»: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. Review. J. Clin. Oncol. 2008; 26 (18): 3063–72.
  8. Oberndorfer S. Kazinoide tumoren des Dunndarms. Z Pathol. Frankf. 1907; 1: 426–32.
  9. Soga J. The term «carcinoid» is a misnomer: the evidence based on local invasion. J. Exp. Clin. Cancer Res. 2009; 28: 15.
  10. Öberg K. Carcinoid tumors: molecular genetics, tumor biology, and update of diagnosis and treatment. Curr. Opin. Oncol. 2002; 14: 38–45.
  11. Klöppel G. Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms. Endocr. Relat. Cancer. 2011; 18: 1–16.
  12. Moran C.A., Suster S., Coppola D., Wick M.R. Neuroendocrine carcinomas of the lung: a critical analysis. Am. J. Clin. Pathol. 2009; 131 (2): 206–21.
  13. Bosman F.T., Carneiro F.T., Hrubon R.H. et al. (Eds) World Health Organization Classification of Tumours, Pathology and Genetics of Tumours of the Digestive System. IARC Press: Lyon. France. 2010.
  14. Travis W.D, Brambilla E., Müller-Hermelink H.K., Har ris C.C. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. World Health Organization Classification of Tumours. 2004. Vol. 10. IARC Press: Lyon, France.
  15. Rindi G., Wiedenmann B. Neuroendocrine neoplasms of the gut and pancreas: new insights. Nat. Rev. Endocrinol. 2011; 8 (1): 54–64.
  16. Reid M.D., Balci S., Saka B., Adsay N.V. Neuroendocrine tumors of the pancreas: current concepts and controversies. Endocr. Pathol. 2014; 25 (1): 65–79.
  17. Rekhtman N. Neuroendocrine Tumors of the Lung: An Update. Arch. Pathol. Lab. Med. 2010; 134 (11): 1628–38.
  18. Travis W.D. Advances in neuroendocrine lung tumors. Ann. Oncol. 2010; 21 (Suppl. 7): 65–71.
  19. Travis W.D. Update on small cell carcinoma and its differentiation from squamous cell carcinoma and other non-small cell carcinomas. Mod. Pathol. 2012; 25 (Suppl. 1): 18–30.
  20. Scoazec J.Y., Couvelard A. Gastroenteropancreatic neuroendocrine tumors: what must the pathologist know and do in 2014? Ann. Pathol. 2014; 34 (1): 40–50.
  21. Shi C., Klimstra D.S. Pancreatic neuroendocrine tumors: pathologic and molecular characteristics. Semin. Diagn. Pathol. 2014; 30: piiS0740-2570.
  22. Klimstra D.S. Pathology reporting of neuroendocrine tumors: essential elements for accurate diagnosis, classification, and staging. Semin. Oncol. 2013; 40 (1): 23–36.
  23. DeLellis R.A., Shin S.J., Treaba O.D. Chapter 10: Immunohistology of Endocrine Tumors. In: Dabbs D.J. ed. Diagnostic Immunohistochemistry: Theranostic and Genomic Applications. 3rd Edition. Elsevier Inc. 2010; 291–329.
  24. Leteurtre E. Pathologic diagnostic for a primary of metastatic neuroendocrine tumor. Ann. Pathol. 2011; 31 (5 Suppl.): 79–80.
  25. Sagi A., Alexis D., Remotti F., Bhagat G. Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary carcinoids. Am. J. Clin. Pathol. 2005; 123 (3): 394–404.
  26. Schmitt A.M., Riniker F., Anlauf M. Islet 1 (Isl1) expression is a reliable marker for pancreatic endocrine tumors and their metastases. Am. J. Surg. Pathol. 2008; 32 (3): 420-25.
  27. Srivastava A., Hornick J.L. Immunohistochemical staining for CDX-2, PDX-1, NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am. J. Surg. Pathol. 2009; 33 (4): 626–32.
  28. Couvelard A. Ki67 and neuroendocrine tumors. Ann. Pathol. 2011; 31 (5 Suppl.): 55–6.
  29. Klöppel G., Rindi G., Perren A. et al. The ENETS and AJCC/UICC TNM classifications of the neuroendocrine tumors of the gastrointestinal tract and the pancreas: a statement. Virchows Arch. 2010; 456 (6): 595–7.
  30. Yang M., Tian B.L., Zhang Y. et al. Evaluation of the World Health Organization 2010 grading system in surgical outcome and prognosis of pancreatic neuroendocrine tumors. Pancreas. 2014; 43 (7): 1003–8.
  31. Rindi G., Klersy C., Inzani F. et al. Grading the neuroendocrine tumors of the lung: an evidence-based proposal. Endocrine-Related Cancer. 2014; 21 (1): 1–16.
  32. Jamali M., Chetty R. Predicting prognosis in gastroentero-pancreatic neuroendocrine tumors: an overview and the value of Ki-67 immunostaining. Endocr. Pathol. 2008; 19 (4): 282–88.
  33. Boussaha T., Rougier P., Taieb J., Lepere C. Digestive neuroendocrine tumors (DNET): the era of targeted therapies. Clin. Res. Hepatol. Gastroenterol. 2013; 37 (2): 134–41.
  34. Oberg K.E., Reubi J.C., Kwekkeboom D.J., Krenning E.P. Role of somatostatins in gastroentropancreatic neuroendocrine tumor development and therapy. Gastroenterol. 2010; 139 (3): 742–53.
  35. Sidéris L., Dubé P., Rinke A. Antitumor effects of somatostatin analogs in neuroendocrine tumors. Oncologist. 2012; 17 (6): 747–55.
  36. Strosberg J., Kvols L. Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors. World Gastroenterol. 2010; 16 (24): 2963–70.
  37. Körner M., Waser B., Schonbrunn A. et al. Somatostatin receptor subtype 2a immunohistochemistry using a new monoclonal antibody selects tumors suitable for in vivo somatostatin receptor targeting. Am. J. Surg. Pathol. 2012; 36 (2): 242–52.
  38. Wolin E.M. PI3K/Akt/mTOR pathway inhibitors in the therapy of pancreatic neuroendocrine tumors. Cancer Lett. 2013; 335 (1): 1–8.
  39. Cingarlini S., Bonomi M., Corbo V. Profiling mTOR pathway in neuroendocrine tumors. Target Oncol. 2012; 7 (3): 183–8.
  40. Qian Z.R., Ter-Minassian M., Chan J.A. et al. Prognostic significance of MTOR pathway component expression in neuroendocrine tumors. J. Clin. Oncol. 2013; 31 (27): 3418–25.
  41. Kulke M.H., Hornick J.L., Frauenhoffer C. et al. O6-methylguanine DNA methyltransferase deficiency and response to temozolomide-based therapy in patients with neuroendocrine tumors. Clin. Cancer Res. 2009; 15 (1): 338–45.
  42. Schmitt A.M., Pavel M., Rudolph T. et al. Prognostic and predictive roles of MGMT protein expression and promoter methylation in sporadic pancreatic neuroendocrine neoplasms. Neuroendocrinology. 2014; 100 (1): 35–44.
  43. Abdel-Rahman O. Vascular endothelial growth factor (VEGF) pathway and neuroendocrine neoplasms (NENs): prognostic and therapeutic considerations. Tumour Biol. 2014; 35 (11): 10615–25.
  44. Scoazec J.Y. Angiogenesis in neuroendocrine tumors: therapeutic applications. Neuroendocrinology. 2013; 97 (1): 45–56.
  45. Gilbert J.A., Adhikari L.J., Lloyd R.V. et al. Molecular markers for novel therapeutic strategies in pancreatic endocrine tumors. Pancreas. 2013; 42 (3): 411–21.