Diagnostic Histopathology
Volume 15, Issue 12 , Pages 554-563 , December 2009

Molecular genetics of endometrial carcinoma

References 

  1. American Cancer Society . Cancer facts and figures 2009. Atlanta, GA: American Cancer Society; 2009;
  2. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15:10–17
  3. Tashiro H, Isacson C, Levine R, Kurman RJ, Cho KR, Hedrick L. p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis. Am J Pathol. 1997;150:177–185
  4. Lax SF, Kendall B, Tashiro H, Slebos RJ, Hedrick L. The frequency of p53, K-Ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways. Cancer. 2000;88:814–824
  5. Berchuck A, Rodriguez G, Kinney RB, et al. Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease. Am J Obstet Gynecol. 1991;164:15–21
  6. Tritz D, Pieretti M, Turner S, Powell D. Loss of heterozygosity in usual and special variant carcinomas of the endometrium. Hum Pathol. 1997;28:607–612
  7. Burks RT, Kessis TD, Cho KR, Hedrick L. Microsatellite instability in endometrial carcinoma. Oncogene. 1994;9:1163–1166
  8. Duggan BD, Felix JC, Muderspach LI, Tourgeman D, Zheng J, Shibata D. Microsatellite instability in sporadic endometrial carcinoma. J Natl Cancer Inst. 1994;86:1216–1221
  9. Catasus L, Machin P, Matias-Guiu X, Prat J. Microsatellite instability in endometrial carcinomas clinicopathologic correlations in a series of 42 cases. Hum Pathol. 1998;29:1160–1164
  10. Tashiro H, Blazes MS, Wu R, et al. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res. 1997;57:3935–3940
  11. Risinger JI, Hayes K, Maxwell GL, et al. PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics. Clin Cancer Res. 1998;4:3005–3010
  12. Maxwell GL, Risinger JI, Gumbs C, et al. Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias. Cancer Res. 1998;58:2500–2503
  13. Bussaglia E, del Rio E, Matias-Guiu X, Prat J. PTEN mutations in endometrial carcinomas: a molecular and clinicopathologic analysis of 38 cases. Hum Pathol. 2000;31:312–317
  14. Salvesen HB, Stefansson I, Kretzschmar EI, et al. Significance of PTEN alterations in endometrial carcinoma: a population-based study of mutations, promoter methylation and PTEN protein expression. Int J Oncol. 2004;25:1615–1623
  15. Oda K, Stokoe D, Taketani Y, McCormick F. High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res. 2005;65:10669–10673
  16. Velasco A, Bussaglia E, Pallares J, et al. PIK3CA gene mutations in endometrial carcinoma. Correlation with PTEN and K-Ras alterations. Hum Pathol. 2006;37:1465–1472
  17. Hayes MP, Wang H, Espinal-Witter R, et al. PIK3CA and PTEN mutations in uterine endometrioid carcinoma and complex atypical hyperplasia. Clin Cancer Res. 2006;12:5932–5935
  18. Catasus L, Gallardo A, Cuatrecasas M, Prat J. PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters. Mod Pathol. 2008;21:131–139
  19. Enomoto T, Inoue M, Perantoni AO, et al. K-Ras activation in premalignant and malignant epithelial lesions of the human uterus. Cancer Res. 1991;51:5308–5314
  20. Lagarda H, Catasus L, Arguelles R, Matias-Guiu X, Prat J. K-Ras mutations in endometrial carcinomas with microsatellite instability. J Pathol. 2001;193:193–199
  21. Sasaki H, Nishii H, Tada A, et al. Mutation of the Ki-Ras protooncogene in human endometrial hyperplasia and carcinoma. Cancer Res. 1993;53:1906–1910
  22. Fukuchi T, Sakamoto M, Tsuda H, Maruyama K, Nozawa S, Hirohashi S. Beta-catenin mutations in carcinoma of the uterine endometrium. Cancer Res. 1998;58:3526–3528
  23. Schlosshauer PW, Pirog EC, Levine RL, Ellenson LH. Mutational analysis of the CTNNB1 and APC genes in uterine endometrioid carcinoma. Mod Pathol. 2000;13:1066–1071
  24. Machin P, Catasus L, Pons C, Muñoz J, Matias-Guiu X, Prat J. CTNNB1 mutations and beta-catenin expression in endometrial carcinomas. Hum Pathol. 2002;33:206–212
  25. Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutation in simple repeated sequences reveals a new mechanism for colonic carcinogenesis. Nature. 1993;363:558–561
  26. Thibodeau SN, Bren G, Schaid V. Microsatellite instability in cancer of the proximal colon. Science. 1993;260:816–819
  27. Esteller M, Levine R, Baylin SB, Ellenson LH, Herman JG. MLH1 promoter hypermethylation is associated with the microsatellite instability phenotype in sporadic endometrial carcinomas. Oncogene. 1998;17:2413–2417
  28. Esteller M, Catasus L, Matias-Guiu X, et al. hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis. Am J Pathol. 1999;155:1767–1772
  29. Maxwell GL, Risinger JI, Alvarez AA, Barrett JC, Berchuck A. Favorable survival associated with microsatellite instability in endometrioid endometrial cancers. Obstet Gynecol. 2001;97:417–422
  30. Black D, Soslow RA, Levine DA, et al. Clinicopathologic significance of defective DNA mismatch repair in endometrial carcinoma. J Clin Oncol. 2006;24:1745–1753
  31. An HJ, Kim KI, Kim JY, et al. Microsatellite instability in endometrioid type endometrial adenocarcinoma is associated with poor prognostic indicators. Am J Surg Pathol. 2007;31:846–853
  32. Catasus L, Matias-Guiu X, Machin P, Muñoz J, Prat J. BAX somatic frameshift mutations in endometrioid adenocarcinomas of the endometrium: evidence for a tumor progression role in endometrial carcinomas with microsatellite instability. Lab Invest. 1998;78:1439–1444
  33. Gurin CC, Federici MG, Kang L, Boyd J. Causes and consequences of microsatellite instability in endometrial carcinoma. Cancer Res. 1999;59:462–466
  34. Catasus L, Matias-Guiu X, Machin P, et al. Frameshift mutations at coding mononucleotide repeat microsatellites in endometrial carcinoma with microsatellite instability. Cancer. 2000;88:2290–2297
  35. Vassileva V, Millar A, Briollais L, Chapman W, Bapat B. Genes involved in DNA repair are mutational targets in endometrial cancers with microsatellite instability. Cancer Res. 2002;62:4095–4099
  36. Vassileva V, Millar A, Briollais L, Chapman W, Bapat B. Apoptotic and growth regulatory genes as mutational targets in mismatch repair deficient endometrioid adenocarcinomas of young patients. Oncol Rep. 2004;11:931–937
  37. Catasus L, Gallardo A, Cuatrecasas M, Prat J. Concomitant PI3K-AKT and p53 alterations in endometrial carcinomas are associated with poor prognosis. Mod Pathol. 2009;22:522–529
  38. 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;92:924–930
  39. Bilbao C, Rodriguez G, Ramirez R, et al. The relationship between microsatellite instability and PTEN gene mutations in endometrial cancer. Int J Cancer. 2006;119:563–570
  40. Levine RL, Cargile CB, Blazes MS, van Rees B, Kurman RJ, Ellenson LH. PTEN mutations and microsatellite instability in complex atypical hyperplasia, a precursor lesion to uterine endometrioid carcinoma. Cancer Res. 1998;58:3254–3258
  41. Minaguchi T, Yoshikawa H, Oda K, et al. PTEN mutation located only outside exons 5, 6, and 7 is an independent predictor of favorable survival in endometrial carcinomas. Clin Cancer Res. 2001;7:2636–2642
  42. Uegaki K, Kanamori Y, Kigawa J, et al. PTEN-positive and phosphorylated-Akt-negative expression is a predictor of survival for patients with advanced endometrial carcinoma. Oncol Rep. 2005;14:389–392
  43. Oda K, Okada J, Timmerman L, et al. PIK3CA cooperates with other phosphatidylinositol 3′-kinase pathway mutations to effect oncogenic transformation. Cancer Res. 2008;68:8127–8136
  44. Pallarés J, Velasco A, Eritja N, et al. Promoter hypermethylation and reduced expression of RASSF1A are frequent molecular alterations of endometrial carcinoma. Mod Pathol. 2008;21:691–699
  45. Brachtel EF, Sánchez-Estevez C, Moreno-Bueno G, Prat J, Palacios J, Oliva E. Distinct molecular alterations in complex endometrial hyperplasia (CEH) with and without immature squamous metaplasia (squamous morules). Am J Surg Pathol. 2005;29:1322–1329
  46. Moreno-Bueno G, Hardisson D, Sanchez C, et al. Abnormalities of the APC/beta-catenin pathway in endometrial cancer. Oncogene. 2002;21:7981–7990
  47. Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006;66:8319–8326
  48. Sakuragi N, Nishiya M, Ikeda K, et al. Decreased E-cadherin expression in endometrial carcinoma is associated with tumor dedifferentiation and deep myometrial invasion. Gynecol Oncol. 1994;53:183–189
  49. Mell LK, Meyer JJ, Tretiakova M, et al. Prognostic significance of E-cadherin protein expression in pathological stage I-III endometrial cancer. Clin Cancer Res. 2004;10:5546–5553
  50. Moreno-Bueno G, Hardisson D, Sarrio D, et al. Abnormalities of E- and P-cadherin and catenin (beta-, gamma-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia. J Pathol. 2003;199:471–478
  51. Moreno-Bueno G, Cubillo E, Sarrió D, et al. Genetic profiling of epithelial cells expressing E-cadherin repressors reveals a distinct role for Snail, Slug, and E47 factors in epithelial-mesenchymal transition. Cancer Res. 2006;66:9543–9556
  52. Blechschmidt K, Kremmer E, Hollweck R, et al. The E-cadherin repressor snail plays a role in tumor progression of endometrioid adenocarcinomas. Diagn Mol Pathol. 2007;16:222–228
  53. Hipp S, Walch A, Schuster T, Höfler H, Becker KF. Precise measurement of the E-cadherin repressor Snail in formalin-fixed endometrial carcinoma using protein lysate microarrays. Clin Exp Metastasis. 2008;25:679–683
  54. Kyo S, Sakaguchi J, Ohno S, et al. High Twist expression is involved in infiltrative endometrial cancer and affects patient survival. Hum Pathol. 2006;37:431–438
  55. Moll UM, Chalas E, Auguste M, Meaney D, Chumas J. Uterine papillary serous carcinoma evolves via a p53-driven pathway. Hum Pathol. 1996;27:1295–1300
  56. Sherman ME, Bur ME, Kurman RJ. P53 in endometrial cancer and its putative precursors: evidence for diverse pathways of tumorigenesis. Hum Pathol. 1995;26:1268–1274
  57. Trahan S, Tetu B, Raymond PE. Serous papillary carcinoma of the endometrium arising from endometrial polyps: a clinical, histological, and immunohistochemical study of 13 cases. Hum Pathol. 2005;36:1316–1321
  58. Lee C, Kim JS, Waldman T. Activated PI3K signaling as an endogenous inducer of p53 in human cancer. Cell Cycle. 2007;6:394–396
  59. Prat J, Oliva E, Lerma E, Vaquero M, Matías-Guiu X. Uterine papillary serous adenocarcinoma. A 10-case study of p53 and c-erbB-2 expression and DNA content. Cancer. 1994;74:1778–1783
  60. Santin AD, Bellone S, Van Stedum S, et al. Amplification of c-erbB2 oncogene: a major prognostic indicator in uterine serous papillary carcinoma. Cancer. 2005;104:1391–1397
  61. Morrison C, Zanagnolo V, Ramirez N, et al. HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients. J Clin Oncol. 2006;24:2376–2385
  62. Cassia R, Moreno-Bueno G, Rodríguez-Perales S, Hardisson D, Cigudosa JC, Palacios J. Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma. J Pathol. 2003;201:589–595
  63. Moreno-Bueno G, Rodríguez-Perales S, Sánchez-Estévez C, et al. Molecular alterations associated with cyclin D1 overexpression in endometrial cancer. Int J Cancer. 2004;110:194–200
  64. Planaguma J, Abal M, Gil-Moreno A, et al. Up-regulation of ERM/ETV5 correlates with the degree of myometrial infiltration in endometrioid endometrial carcinoma. J Pathol. 2005;207:422–429
  65. Risinger JI, Maxwell GL, Chandramouli GV, et al. Microarray analysis reveals distinct gene expression profiles among different histologic types of endometrial cancer. Cancer Res. 2003;63:6–11
  66. Moreno-Bueno G, Sánchez-Estévez C, Cassia R, et al. Differential gene expresión profile in endometrioid and nonendometrioid endometrial carcinoma: STK15 is frequently overexpressed and amplified in nonendometrioid carcinomas. Cancer Res. 2003;63:5697–5702
  67. Salvesen HB, Carter SL, Mannelqvist M, et al. Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation. Proc Natl Acad Sci USA. 2009;106:4834–4839

PII: S1756-2317(09)00174-1

doi: 10.1016/j.mpdhp.2009.09.002

Diagnostic Histopathology
Volume 15, Issue 12 , Pages 554-563 , December 2009