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Molecular pathology of endometrial carcinoma – a review


Authors: Karol Kajo 1;  Miroslava Vallová 1;  Csaba Biró 1;  Gabriel Bognár 1;  Katarína Macháleková 1;  Katarína Závodná 2;  Štefan Galbavý 1,3;  Pavol Žúbor 4
Authors‘ workplace: Ústav patológie SZU a OÚSA, Bratislava 1;  Oddelenie lekárskej genetiky Ústavu laboratórnej medicíny OÚSA, Bratislava 2;  Ústav súdneho lekárstva LF UK, Bratislava 3;  Gynekologicko-pôrodnícka klinika JLF UK a UNM, Martin 4
Published in: Čes.-slov. Patol., 51, 2015, No. 2, p. 65-73
Category: Reviews Article

Overview

Endometrial carcinoma (EC) is the most common malignancy of the female genital tract in developed countries. According to its histomorphologic characteristics EC is divided into endometroid and serous carcinoma; among less common subtypes there are clear cell, mucinous, neuroendocrine and undifferentiated carcinoma and carcinosarcoma. Endometroid and serous EC were essential for the so-called dual classification of EC (type I and type II), which considered mainly epidemiological, clinical and endocrine characteristics.

It was shown that part of the high-grade serous carcinomas (type II) can develop from the endometroid EC by a multiplication of genomic changes and there are also EC, in which both basic types are overlapping. Today it is known that clinical and histological presentation of the EC reflects the genetic and epigenetic alterations affecting mainly PTEN, PIK3CA, KRAS, CTNNB1 and TP53 genes, or leading to microsatellite instability. However, these changes are variably present in both types of EC; therefore dual division of EC has appeared very rigid.

The novel classifications should represent an integrated system which also incorporates the results of the gene expression analyses and multiparallel DNA sequencing. Based on these findings EC were divided into four molecular categories: a) POLE/ultra mutated; b) hyper mutated microsatellite instable; c) “copy number low” d) “copy number high” serous-like carcinoma. This division better reflects the biological characteristics of each EC and represents a base for the individual therapy.

Keywords:
endometrium – carcinoma – immunohistochemistry – genetics


Sources

1. Matias-Guiu X, Prat J. Molecular pathology of endometrial carcinoma. Histopathology 2013; 62(1): 111-123.

2. Safaei-Diba Ch, Pleško I, Hlava P. Incidencia zhubných nádorov v Slovenskej republike 2007. Národný onkologický register SR, NCZI: Bratislava; 2012: 136.

3. Yeramian A, Moreno-Bueno G, Dolcet X, et al. Endometrial carcinoma: molecular alterations involved in tumor development and progression. Oncogene 2013; 32(4): 403-413.

4. Murali R, Soslow RA, Weigelt B. Classification of endometrial carcinoma: more than two types. Lancet Oncol 2014; 15(7): e268-e278.

5. McConechy MK, Ding J, Cheang MC, et al. Use of mutation profiles to refine the classification of endometrial carcinomas. J Pathol 2012; 228(1): 20-30.

6. Prat J, Gallaro A, Coutrecasas M, Catasús L. Endometrial carcinoma: pathology and genetics. Pathology 2007; 39(1): 72-87.

7. Nakayama K, Nakayama N, Ishikawa M, Miyazali K. Endometrial serous carcinoma: its molecular characteristics and histology-specific treatment strategies. Cancers (Basel) 2012; 4(3): 799-807.

8. Zaino R, Carinelli SG, Ellenson LH, et al. Epithelial tumours and precursors. In: Kurman RJ, Carcangiu ML, Herrington CS, Young RH, eds. WHO Classification of tumours of female reproductive organs. Lyon: IARC; 2014: 125-135.

9. Kandoth C, Schultz N, Cherniack AD, et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013; 497(7447): 67-73.

10. Ma X, Gao X. Epigenetic modification and carcinogenesis of human endometrial cancer. Austin J Clin Pathol 2014; 1(3): 9.

11. Hatzimichael E, Crook T. Cancer epigenetics: new therapies and new challenges. J Grug Deliv 2013; 2013: 529312.

12. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15(1): 10-17.

13. Abal M, Planaguma J, Gil-Moreno A, et al. Molecular pathology of endometrial carcinoma: transcriptional signature in endometroid tumors. Histol Histopathol 2006; 21(2): 197-204.

14. Doll A, Abal M, Rigau M, et al. Novel molecular profiles of endometrial cancer – new light through old window. J Steroid Biochem Mol Biol 2008: 108(3-5): 221-229.

15. Okuda T, Sekizawa A, Purwosunu Y, et al. Genetics of Endometrial Cancers. Obstet Gynecol Int 2010; 2010: 984013.

16. Llobet D, Pallares J, Yeramian A, et al. Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints. J Clin Pathol 2009; 62(9): 777-785.

17. Banno K, Nogami Y, Kisu I, et al. Candidate Biomarkers for Genetic and Clinicopathological Diagnosis of Endometrial Cancer. Int J Mol Sci 2013; 14(6): 12123-12137.

18. Bansal N, Yenduri V, Wenham RM. The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control 2009; 16(1): 8-13.

19. Fiolka R, Zubor P, Janusicova V, et al. Promoter hypermethylation of the tumor-suppressor genes RASSF1A, GSTP1 and CDH1 in endometrial cancer. Oncol Rep 2013; 30(6): 2868-2871.

20. Mutter GL, Lin MC, Fitzgerald JT, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000; 92(11): 924-931.

21. Mutter GL. PTEN, a protean tumor suppressor. Am J Pathol 2001; 158(6): 1895–1898.

22. Merritt MA, Cramer DW. Molecular pathogenesis of endometrial and ovarian cancer. Cancer Biomark (2010); 9(1-6): 287–305.

23. Baak JP, Mutter GL, Robboy S, et al. The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system. Cancer 2005; 103(11): 2304–2312.

24. Sherman ME, Bur ME, Kurman RJ. p53 in endometrial cancer and its putative precursors: evidence for diverse pathways of tumorigenesis. Hum Pathol 1995; 26(11): 1268-1274.

25. Zheng W, Liang SX, Yu H, Rutherford T, Cham­bers SK, Schwartz PE. Endometrial glandu­lar dysplasia: a newly defined precursor lesion of uterine papillary serous carcinoma. Part I: morphologic features. Int J Surg Pathol 2004; 12(3): 207-223.

26. Zheng W, Xiang L, Fadare O, Kong B. A pro­posed model for endometrial serous carcino­genesis. Am J Surg Pathol 2011; 35(1): e1-e14.

27. Han LM, Wei L, Ferguson DC, Chambers SK, Fadare O, Wang Y, Zheng W. From endometrial glandular dysplasia to endometrial serous carcinoma: insights into underlying biological aspects. Am J Clin Obstet Gynecol 2013; 1(1): 1-16.

28. Zubor P, Stanclova A, Kajo K, et al. The p53 codon 72 exon 4 BstUI polymorphism and endometrial cancer in Caucasian women. Oncology 2009; 76: 173-83.

29. Kafshdooz T, Tabrizi AD, Ardabili SMM, et al. Polymorphism of p53 Gene Codon 72 in Endometrial Cancer: Correlation with Tumor Grade and Histological Type. Asian Pac J Cancer Prev 2014; 15(22): 9603-9606.

30. Sung CO, Sohn I. The expression pattern of 19 genes predicts the histology of endometrial carcinoma. Sci Rep 2014; 4: 5174.

31. Dong P, Konno Y, Watari H, Hosaka M, Noguchi M, Sakuragi N. The impact of microRNA- mediated PI3K/AKT signalling on epithelial-mesenchymal transition and cancer stemness in endometrial cancer. J Transl Med 2014; 12: 231.

32. Soslow RA. High-grade endometrial carcinomas – strategies for typing. Histopathology 2013; 62(1): 89-110.

33. Ma X, Ma CX, Wang J. Endometrial carcinogenesis and molecular signaling pathways. Am J Mol Biol 2014; 4: 134-149.

34. Zhang B, Xing X, Li J, et al. Comparative DNA methylome analysis of endometrial carcinoma reveals complex and distinct deregulation of cancer promoters and enhancers. BMC Genomics 2014; 15: 868.

35. Dvořáková E, Chmelařová M, Laco J, Palička J, Špaček J. Methylation analysis of tumor suppressor genes in endometroid carcinoma of endometrium using MS-MLPA. Biomed Pap Med Fac Univ Palacky Olomouc Czech Republ 2013; 157(4): 298-303.

36. Hiroki E, Suzuki F, Akahira J, et al. MicroRNA-34b function as a potential tumor suppressor in endometrial serous adenocarcinoma. Int J Cancer 2012; 131(4): E395-404.

37. Kuhn E, Wu RC, Guan B, et al. Identification of molecular pathway aberrations in uterine serous carcinoma by genome-wide analyses. J Natl Cancer Inst 2012; 104(19): 1503-1513.

38. Le Gallo M, O’Hara AJ, Rudd ML, et al. Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin remodeling and ubiquitin ligase complex genes. Nat Genet 2012; 44(12): 1310-1315.

39. Zhao S, Choi M, Overton JD, et al. Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma. Proc Natl Acad Sci USA 2013; 110(8): 2916-2921.

40. Liang H, Cheung LW, Li J, et al. Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer. Genome Res 2012; 22(11): 2120-2129.

41. Kinde I, Bettegowda C, Wang Y, et al. Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers. Sci Transl Med 2013; 5(167): 167ra4.

42. Bell DW. Novel genetic targets in endometrial cancer. Exp Opin Ther Targets 2014; 18(7): 725-730.

43. Salvesen HB, Haldorsen IS, Trovik J. Markers for individualized therapy in endometrial carcinoma. Lancet Oncol 2012; 13(8): e353-361.

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