CUP-синдром: современный взгляд на проблему (обзор литературы)

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Аннотация

Опухоли без выявленного первичного очага (CUP-синдром) – интригующий клинический феномен, который ежегодно регистрируется у 5% пациентов с вновь выявленными злокачественными новообразованиями. Отсутствие клинических проявлений первичной опухоли, развитие ранних, необычных, зачастую множественных метастазов – признаки этой гетерогенной группы новообразований. Однако не существует единого мнения, является ли CUP-синдром метастазами невыявленной первичной опухоли, или это самостоятельное биологическое явление с определенными генетическими и фенотипическими особенностями. Идентификация основных молекулярных отклонений, характеризующих CUP-синдром, медленно, но прогрессирует. Профиль генной экспрессии и экспрессии микро-РНК являются высокоспецифичными тестами, которые должны помочь определить гистогенез опухолей без выявленного первичного очага.

Ключевые слова: опухоли без выявленного первичного очага, CUP-синдром.

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Tumors of unknown primary site (CUP-syndrome) – an intriguing clinical phenomenon that each year 5% of patients with newly diagnosed malignancies. The absence of clinical manifestations of the primary tumor, early development, unusual, often multiple metastases – signs of this heterogeneous group of neoplasms. However, there is no consensus whether the CUP-syndrome metastases undetected primary tumor or an independent biological phenomenon with certain genetic and phenotypic characteristics. Identification of major molecular abnormalities that characterize CUP-syndrome, slow progressive. Profile of gene expression and the expression of miRNAs are highly specific tests that can help to identify histogenesis of tumors without primary site.

Key words: unknown primary tumours, CUP-syndrome.

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Список литературы

1. Комаров И.Г., Комов Д.В. Метастазы злокачественных опухолей без выявленного первичного очага. Энциклопедия клинической онкологии. М.: РЛС, 2004.
2. Минимальные клинические рекомендации Европейского общества медицинской онкологии. М., 2008.
3. Abbruzzese JL, Abbruzzese MC, Hess KR. Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. J Clin Oncol 1994; 12: 1272–80.
4. Abeloff MD, Armitage JO, Lichter AS et al. Unknown primary in clinical oncology. Churchill Livingstone. NY 1995; p. 1833–45.
5. Altman E, Cadman E. An analysis of 1539 patients with cancer of unknown primary site. Cancer 1986; 57 (1): 120–4.
6. Bar-Eli M, Abbruzzese JL, Lee-Jackson D et al. P53 gene mutation spectrum in human unknown primary tumors. Anticancer Res 1993; 13: 1619–23.
7. Bloom G, Yang IV, Boulware D et al. Multi-platform, multi-site, microarray-based human tumor classification. Am J Pathol 2004; 164: 9–16.
8. Briasoulis E, Tsokos M et al. Bcl-2 and p53 protein expression in metastatic carcinoma of unknown primary origin. Biological and clinical implications. A Hellenic Cooperative Oncology Group study. Anticancer Res 1998; 18: 1907–14.
9. Chevalier TL, Cvitkovic E, Caille P. Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients. Arch Intern Med 1988; 148: 2035–9.
10. Chorost MI, Lee MC, Yeoh CB. Unknown primary. J Surg Oncol 2004; 87: 191–203.
11. Culine S, Kramar A, Saghatchian M et al. Development and validation of a prognostic model to predict the length of survival in patients with carcinomas of an unknown primary site. J Clin Oncol 2002; 20 (24): 4679–83.
12. Gaast A, Verweij J, Planting AS et al. Fluorouracil, doxorubicin and mitomycin C: (FAM) combination chemotherapy for metastatic adenocarcinoma of unknown primary. Eur J Cancer Clin Oncol 1988; 24 (4): 765–8.
13. Greco FA, Hainsworth JD. Tumors of unknown origin. Cancer J Clin 1992; 42: 96–115.
14. Greco FA. Cancer of unknown primary site: evolving understanding and management of patients. Clin Advanc Hematol Oncol 2012; 10 (8): 518–24.
15. Haldar S, Basu A, Croce CM. Bcl-2 is the guardian of microtubule integrity. Cancer Res 1997; 57: 229–33.
16. Hillen HF. Unknown primary tumours review. Postgrad Med J 2000; 76: 690–3.
17. Hollstein M, Sidransky D, Vogelstein B. P53 mutations in human cancers. Science 1991; 253: 49–53.
18. Ilson DH, Motzer RJ, Rodriguez E et al. Genetic analysis in the diagnosis of neoplasms of unknown primary tumor site. Semin Oncol 1993; 20: 229–37.
19. Kirsten F, Chi CH, Leary JA. Metastatic adeno or undifferentiated carcinoma from unknown primary site – natural history and guidelines for identification of treatable subsets. Q J Med 1987; 62: 143–61.
20. Krämer A, Gattenlöhner S, Neben K. CUP-Syndrom. Molekulare pathogenese und biologie pathologe 2009; 30: 117–24.
21. Lembersky BC, Thomas LC. Metastases of unknown primary site. Med Clin North Am 1996; 80 (1): 153–71.
22. Leonard RJ, Nystrom JS. Diagnostic evaluation of patients with carcinoma of unknown primary site. Semin Oncol 1993; 20: 244–50.
23. Levi F, Te VC et al. Epidemiology of unknown primary tumour. Eur J Cancer 2002; 38: 1890–12.
24. Moll R. Initial CUP-Situation und CUP-Syndrom Pathologische Diagnostik. Pathologe 2009; 30 (Suppl. 2): 161–7.
25. Motzer RJ, Rodriguez E, Reuter VE et al. Molecular and cytogenetic studies in the diagnosis of patients with poorly differentiated carcinomas of unknown primary site. J Clin Oncol 1995; 13: 274–82.
26. Nissenblatt MJ. Carcinoma with unknown primary tumor (CUP syndrome). South Med J 1981; 74: 1497–502.
27. Nystrom JS, Weiner JM, Heffelfinger-Juttner J. Metastatic and histologic presentation in unknown primary cancer. Semin Oncol 1997; 4: 53–8.
28. Pantou D, Tsarouha H, Papadopoulou A. Cytogenetic profile of unknown primary tumors: clues for their pathogenesis and clinical management. Neoplasia 2003; 5: 23–31.
29. Pavlidis N, Briasoulis E, Hainsworth J. Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer 2003; 39: 1990–2005.
30. Pavlidis N. Forty years experience of treating cancer of unknown primary. Acta Oncol 2007; 46: 592–601.
31. Pavlidis N, Wick MR. Metastatic carcinomas of unknown primary origin. Chemotherapy NY. Demos Medical Publishing 2008; p. 225–34.
32. Pavlidis N, Fizazi K. Carcinoma of unknown primary (CUP) critical reviews. Oncol Hematol 2009; 69: 271–8.
33. Pavlidis N, Pentheroudakis G. Cancer of unknown primary site: 20 questions to be answered. Ann Oncol 2010; 21 (7): 303–7.
34. Pavlidis N, Pentheroudakis G. Cancer of unknown primary site. Lancet 2012; 379: 1428–5.
35. Pentheroudakis G, Briasoulis E, Pavlidis N. Cancer of unknown primary site: missing primary or missing biology. Oncologist 2007; 12: 418–25.
36. Petersen I, Hidalgo A, Petersen S. Chromosomal imbalances in brain metastases of solid tumors. Brain Pathol 2000; 10: 395–401.
37. Rosenfeld N, Aharonov R, Meiri E et al. Micro RNAs accurately identify cancer tissue origin Nat Biotechnology 2008; 26: 462–9.
38. Soong R, Robbins PD, Dix BR et al. Concordance between p53 protein overexpression and gene mutation in a large series of common human carcinomas. Hum Pathol 1996; 27: 1050–5.
39. Su AI, Welsh JB, Sapinoso LM et al. Molecular classification of human carcinomas by use of gene expression signatures. Cancer Res 2001; 61: 7388–93.
40. Summersgill B, Goker H, Osin P et al. Establishing germ cell origin of undifferentiated tumors by identifying gain of 12p material using comparative genomic hybridization analysis of paraffin-embedded samples. Diagn Mol Pathol 1998; 7: 260–6.
41. Tothill RW, Kowalczyk A, Rischin D et al. An expression-based site of origin diagnostic method designed for clinical application to cancer of unknown origin. Cancer Res 2005; 65: 4031–40.
42. Varadhachary GR, Abbruzzese JL, Lenz R. Diagnostic strategies for unknown primary cancer. Cancer 2004; 100: 1776–85.
43. Visser O, Coebergh JW, Schouten LJ. Incidence of cancer in the Netherlands. Netherlands Cancer Registry Utrecht 1993.
44. Vousden KH, Woude GF. The ins and outs of p5. Nat Cell Biol 2000; p. 178–80.
45. Wouw AJ, Janssen-Heijnen ML Coebergh JW. Epidemiology of unknown primary tumours; incidence and population-based survival of 1285 patients in Southeast Netherlands 1984–1992. Eur J Cancer 2002; 3: 409–13.
46. Wouw AJ, Jansen RL, Speel EJ. The unknown biology of the unknown primary tumour: a literature review. Ann Oncol 2003; 14: 191–6.
47. Wouw AJ, Jansen RL, Griffioen AW. Clinical and Immunohistochemical analysis of patients with unknown primary tumour. A search for prognostic factors in UPT. Anticancer Research 2004; 24: 297–302.

Авторы

Н.В.Левицкая1, V.Lewitzki2, И.Г.Комаров3, М.В.Немцова4, И.В.Поддубная1

1 Кафедра онкологии ГБОУ ДПО РМАПО, Москва
2 Universitätsklinikum Rostock Klinik für Strahlentherapie Südring 75 18059, Rostock, Deutschland
3 Федеральное государственное бюджетное учреждение "Российский онкологический научный центр им. Н. Н. Блохина» Российской академии медицинских наук
4 Кафедра медицинской генетики ГБОУ ДПО РМАПО, Москва

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N.V.Levitskaya, V.Lewitzki, I.G.Komarov, M.V.Nemtsova, I.V.Poddubnaya

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