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01-03-2004 | Review Article

Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification

Author: Sigurd F. Lax

Published in: Virchows Archiv | Issue 3/2004

Abstract

Two types of endometrial carcinoma are distinguished with respect to biology and clinical course. Type-I carcinoma is related to hyperestrogenism by association with endometrial hyperplasia, frequent expression of estrogen and progesterone receptors and younger age, whereas type-II carcinoma is unrelated to estrogen, associated with atrophic endometrium, frequent lack of estrogen and progesterone receptors and older age. Histologically, endometrioid and mucinous carcinomas are considered type I, serous and clear cell carcinomas type II. Molecular data from multiple studies support the hypothesis of different genetic pathways in the development of endometrioid and serous carcinoma. The most frequent genetic alteration in endometrioid carcinoma is PTEN inactivation by mutation, followed by microsatellite instability (MIN) and mutations of K-ras and β-catenin. PTEN and K-ras mutations and MIN are considered early events, occurring in a subset of atypical endometrial hyperplasia, whereas p53 mutation is considered a late event, during progression of about 10–20% of endometrioid carcinomas. In serous carcinoma, p53 mutation is the most frequent genetic alteration, followed by inactivation of p16 and e-cadherin and amplification of her2/neu. p53 mutation occurs in endometrial intraepithelial carcinoma, the putative precursor of serous carcinoma. Considering these genetic pathways, the current histological classification of endometrial carcinoma is molecular based.

Aarnio M, Mecklin JP, Aaltonen LA, Nystrom Lahti M, Jarvinen HJ (1995) Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Int J Cancer 64:430–433PubMed

Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, Peltomaki P, Mecklin JP, Jarvinen HJ (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81:214–218CrossRefPubMed

Abeler VM, Vergote IB, Kjorstad KE, Trope CG (1996) Clear cell carcinoma of the endometrium. Prognosis and metastatic pattern. Cancer 78:1740–1747CrossRefPubMed

Albertson DG, Collins C, McCormick F, Gray JW (2003) Chromosome aberrations in solid tumors. Nat Genet 34:369–376CrossRefPubMed

Ambros RA, Sherman ME, Zahn CM, Bitterman P, Kurman RJ (1995) Endometrial intraepithelial carcinoma: a distinctive lesion specifically associated with tumors displaying serous differentiation. Hum Pathol 26:1260–1267PubMed

Baak JP, Path FR, Hermsen MA, Meijer G, Schmidt J, Janssen EA (2003) Genomics and proteomics in cancer. Eur J Cancer 39:1199–1215CrossRefPubMed

Berends MJ, Hollema H, Wu Y, van Der Sluis T, Mensink RG, ten Hoor KA, Sijmons RH, de Vries EG, Pras E, Mourits MJ, Hofstra RM, Buys CH, Kleibeuker JH, and van Der Zee AG (2001) MLH1 and MSH2 protein expression as a pre-screening marker in hereditary and non-hereditary endometrial hyperplasia and cancer. Int J Cancer 92:398–403CrossRefPubMed

Bokhman JV (1983) Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 15:10–17

Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S (1998) A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257PubMed

10.

Brown GJ, St John DJ, Macrae FA, Aittomaki K (2001) Cancer risk in young women at risk of hereditary nonpolyposis colorectal cancer: implications for gynecologic surveillance. Gynecol Oncol 80:346–349CrossRefPubMed

11.

Burks RT, Kessis TD, Cho KR, Hedrick L (1994) Microsatellite instability in endometrial carcinoma. Oncogene 9:1163–1166PubMed

12.

Caduff RF, Johnston CM, Frank TS (1995) Mutations of the Ki-ras oncogene in carcinoma of the endometrium. Am J Pathol 146:182–188PubMed

13.

Caduff RF, Johnston CM, Svoboda Newman SM, Poy EL, Merajver SD, Frank TS (1996) Clinical and pathological significance of microsatellite instability in sporadic endometrial carcinoma. Am J Pathol 148:1671–1678PubMed

14.

Catasus L, Machin P, Matias Guiu X, Prat J (1998) Microsatellite instability in endometrial carcinomas: clinicopathologic correlations in a series of 42 cases. Hum Pathol 29:1160–1164

15.

Catasus L, Matias-Guiu X, Machin P, Munoz J, Prat J (1998) BAX somatic frameshift mutations in endometrioid adenocarcinomas of the endometrium: evidence for a tumor progression role in endometrial carcinomas with microsatellite instability. Lab Invest 78:1439–1444PubMed

16.

Cirisano FD Jr, Robboy SJ, Dodge RK, Bentley RC, Krigman HR, Synan IS, Soper JT, Clarke-Pearson DL (2000) The outcome of stage I-II clinically and surgically staged papillary serous and clear cell endometrial cancers when compared with endometrioid carcinoma. Gynecol Oncol 77:55–65CrossRefPubMed

17.

de Leeuw WJ, Dierssen J, Vasen HF, Wijnen JT, Kenter GG, Meijers-Heijboer H, Brocker-Vriends A, Stormorken A, Moller P, Menko F, Cornelisse CJ, Morreau H (2000) Prediction of a mismatch repair gene defect by microsatellite instability and immunohistochemical analysis in endometrial tumours from HNPCC patients. J Pathol 192:328–335CrossRefPubMed

18.

Duggan BD, Felix JC, Muderspach LI, Tsao JL, Shibata DK (1994) Early mutational activation of the c-Ki-ras oncogene in endometrial carcinoma. Cancer Res 54:1604–1607PubMed

19.

Enomoto T, Inoue M, Perantoni AO, Terakawa N, Tanizawa O, Rice JM (1990) K-ras activation in neoplasms of the human female reproductive tract. Cancer Res 50:6139–6145PubMed

20.

Enriori CL, Reforzo-Membrives J (1984) Peripheral aromatization as a risk factor for breast and endometrial cancer in postmenopausal women: a review. Gynecol Oncol 17:1–21PubMed

21.

Esteller M, Levine R, Baylin SB, Ellenson LH, Herman JG (1998) MLH1 promoter hypermethylation is associated with the microsatellite instability phenotype in sporadic endometrial carcinomas. Oncogene 17:2413–2417CrossRefPubMed

22.

Esteller M, Catasus L, Matias Guiu X, Mutter GL, Prat J, Baylin SB, Herman JG (1999) hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis. Am J Pathol 155:1767–1772PubMed

23.

Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767PubMed

24.

Geisler JP, Geisler HE, Wiemann MC, Zhou Z, Miller GA, Crabtree W (1999) p53 expression as a prognostic indicator of 5-year survival in endometrial cancer. Gynecol Oncol 74:468–471CrossRefPubMed

25.

Goodfellow PJ, Buttin BM, Herzog TJ, Rader JS, Gibb RK, Swisher E, Look K, Walls KC, Fan MY, Mutch DG (2003) Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers. Proc Natl Acad Sci U S A 100:5908–5913CrossRefPubMed

26.

Gurin CC, Federici MG, Kang L, Boyd J (1999) Causes and consequences of microsatellite instability in endometrial carcinoma. Cancer Res 59:462–466PubMed

27.

Halperin R, Zehavi S, Habler L, Hadas E, Bukovsky I, Schneider D (2001) Comparative immunohistochemical study of endometrioid and serous papillary carcinoma of endometrium. Eur J Gynaecol Oncol 22:122–126PubMed

28.

Holcomb K, Delatorre R, Pedemonte B, McLeod C, Anderson L, Chambers J (2002) E-cadherin expression in endometrioid, papillary serous, and clear cell carcinoma of the endometrium. Obstet Gynecol 100:1290–1295CrossRefPubMed

29.

Ikeda T, Yoshinaga K, Suzuki A, Sakurada A, Ohmori H, Horii A (2000) Anticorresponding mutations of the KRAS and PTEN genes in human endometrial cancer. Oncol Res 7:567–570

30.

Ioffe OB, Papadimitriou JC, Drachenberg CB (1998) Correlation of proliferation indices, apoptosis, and related oncogene expression (bcl-2 and c-erbB-2) and p53 in proliferative, hyperplastic, and malignant endometrium. Hum Pathol 29:1150–1159PubMed

31.

Ito K, Watanabe K, Nasim S, Sasano H, Sato S, Yajima A, Silverberg SG, Garrett CT (1996) K-ras point mutations in endometrial carcinoma: effect on outcome is dependent on age of patient. Gynecol Oncol 63:238–246CrossRefPubMed

32.

Kanaya T, Kyo S, Maida Y, Yatabe N, Tanaka M, Nakamura M, Inoue M (2003) Frequent hypermethylation of MLH1 promoter in normal endometrium of patients with endometrial cancers. Oncogene 22:2352–2360CrossRefPubMed

33.

Katabuchi H, van Rees B, Lambers AR, Ronnett BM, Blazes MS, Leach FS, Cho KR, Hedrick L (1995) Mutations in DNA mismatch repair genes are not responsible for microsatellite instability in most sporadic endometrial carcinomas. Cancer Res 55:5556–5560PubMed

34.

Khalifa MA, Mannel RS, Haraway SD, Walker J, Min KW (1994) Expression of EGFR, HER-2/neu, P53, and PCNA in endometrioid, serous papillary, and clear cell endometrial adenocarcinomas. Gynecol Oncol 53:84–92CrossRefPubMed

35.

Kiechle M, Hinrichs M, Jacobsen A, Luttges J, Pfisterer J, Kommoss F, Arnold N (2000) Genetic imbalances in precursor lesions of endometrial cancer detected by comparative genomic hybridization. Am J Pathol 156:1827–1833PubMed

36.

Kihana T, Hamada K, Inoue Y, Yano N, Iketani H, Murao S, Ukita M, Matsuura S (1995) Mutation and allelic loss of the p53 gene in endometrial carcinoma. Incidence and outcome in 92 surgical patients. Cancer 76:72–78PubMed

37.

Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal cancer. Cell 87:159–170PubMed

38.

Kobayashi K, Sagae S, Nishioka Y, Tokino T, Kudo R (1999) Mutations of the beta-catenin gene in endometrial carcinomas. Jpn J Cancer Res 90:55–59PubMed

39.

Koul A, Willen R, Bendahl PO, Nilbert M, Borg A (2002) Distinct sets of gene alterations in endometrial carcinoma implicate alternate modes of tumorigenesis. Cancer 94:2369–2379CrossRefPubMed

40.

Kowalski LD, Mutch DG, Herzog TJ, Rader JS, Goodfellow PJ (1997) Mutational analysis of MLH1 and MSH2 in 25 prospectively-acquired RER+ endometrial cancers. Genes Chromosomes Cancer 18:219–227CrossRefPubMed

41.

Lax SF, Kurman RJ (1997) A dualistic model for endometrial carcinogenesis based on immunohistochemical and molecular genetic analyses. Verh Dtsch Ges Pathol 81228–81232

42.

Lax SF, Pizer ES, Ronnett BM, Kurman RJ (1998) Clear cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki-67, estrogen, and progesterone receptor expression. Hum Pathol 29:551–558PubMed

43.

Lax SF, Pizer ES, Ronnett BM, Kurman RJ (1998) Comparison of estrogen and progesterone receptor, Ki-67, and p53 immunoreactivity in uterine endometrioid carcinoma and endometrioid carcinoma with squamous, mucinous, secretory, and ciliated cell differentiation. Hum Pathol 29:924–931PubMed

44.

Lax SF, Kendall B, Tashiro H, Slebos RJ, Hedrick L (2000) The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways. Cancer 88:814–824CrossRefPubMed

45.

Lax SF, Abeler VM, Regitnig P (2001) Molecular genetic analysis of endometrial carcinoma: evidence for 2 genetically distinctive entities. Virchows Arch 439:247

46.

Lengauer C, Kinzler KW, Vogelstein B (1997) Genetic instability in colorectal cancers. Nature 386:623–627PubMed

47.

Levine RL, Cargile CB, Blazes MS, van Rees B, Kurman RJ, Ellenson LH (1998) PTEN mutations and microsatellite instability in complex atypical hyperplasia, a precursor lesion to uterine endometrioid carcinoma. Cancer Res 58:3254–3258PubMed

48.

Li LS, Kim NG, Kim SH, Park C, Kim H, Kang HJ, Koh KH, Kim SN, Kim WH, Kim NK (2003) Chromosomal imbalances in the colorectal carcinomas with microsatellite instability. Am J Pathol 163:1429–1436PubMed

49.

Lukes AS, Kohler MF, Pieper CF, Kerns BJ, Bentley R, Rodriguez GC, Soper JT, Clarke-Pearson DL, Bast RC Jr, Berchuck A (1994) Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer. Cancer 73:2380–2385

50.

MacDonald ND, Salvesen HB, Ryan A, Iversen OE, Akslen LA, Jacobs IJ (2000) Frequency and prognostic impact of microsatellite instability in a large population-based study of endometrial carcinomas. Cancer Res 60:1750–1752PubMed

51.

Matias-Guiu X, Catasus L, Bussaglia E, Lagarda H, Garcia A, Pons C, Munoz J, Arguelles R, Machin P, Prat J (2001) Molecular pathology of endometrial hyperplasia and carcinoma. Hum Pathol 32:569–577CrossRefPubMed

52.

Maxwell GL, Risinger JI, Alvarez AA, Barrett JC, Berchuck A (2001) Favorable survival associated with microsatellite instability in endometrioid endometrial cancers. Obstet Gynecol 97:417–422CrossRefPubMed

53.

Milde-Langosch K, Riethdorf L, Bamberger AM, Loning T (1999) P16/MTS1 and pRB expression in endometrial carcinomas. Virchows Arch 434:23–28PubMed

54.

Moreno-Bueno G, Hardisson D, Sarrio D, Sanchez C, Cassia R, Prat J, Herman JG, Esteller M, Matias-Guiu X, Palacios J (2003) Abnormalities of E- and P-cadherin and catenin (beta-, gamma-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia. J Pathol 199:471–478CrossRefPubMed

55.

Moreno-Bueno G, Sanchez-Estevez C, Cassia R, Rodriguez-Perales S, Diaz-Uriarte R, Dominguez O, Hardisson D, Andujar M, Prat J, Matias-Guiu X, Cigudosa JC, Palacios J (2003) Differential gene expression profile in endometrioid and nonendometrioid endometrial carcinoma: STK15 is frequently overexpressed and amplified in nonendometrioid carcinomas. Cancer Res 63:5697–5702PubMed

56.

Mutter GL (2001) Pten, a protean tumor suppressor. Am J Pathol 158:1895–1898PubMed

57.

Mutter GL, Baak JP, Crum CP, Richart RM, Ferenczy A, Faquin WC (2000) Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry. J Pathol 190:462–469CrossRefPubMed

58.

Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA, Weng LP, Eng C (2000) Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 92:924–930CrossRefPubMed

59.

Nakashima R, Fujita M, Enomoto T, Haba T, Yoshino K, Wada H, Kurachi H, Sasaki M, Wakasa K, Inoue M, Buzard G, Murata Y (1999) Alteration of p16 and p15 genes in human uterine tumours. Br J Cancer 80:458–467CrossRefPubMed

60.

Nordstrom B, Strang P, Lindgren A, Bergstrom R, Tribukait B (1996) Endometrial carcinoma: the prognostic impact of papillary serous carcinoma (UPSC) in relation to nuclear grade, DNA ploidy and p53 expression. Anticancer Res 16:899–904PubMed

61.

Palacios J, Catasus L, Moreno Bueno G, Matias Guiu X, Prat J, Gamallo C (2001) Beta- and gamma-catenin expression in endometrial carcinoma. Relationship with clinicopathological features and microsatellite instability. Virchows Arch 438:464–469CrossRefPubMed

62.

Parc YR, Halling KC, Burgart LJ, McDonnell SK, Schaid DJ, Thibodeau SN, Halling AC (2000) Microsatellite instability and hMLH1/hMSH2 expression in young endometrial carcinoma patients: associations with family history and histopathology. Int J Cancer 86:60–66PubMed

63.

Perucho M (1996) Microsatellite instability: the mutator that mutates the other mutator. Nat Med 2:630–631PubMed

64.

Potischman N, Hoover RN, Brinton LA, Siiteri P, Dorgan JF, Swanson CA, Berman ML, Mortel R, Twiggs LB, Barrett RJ, Wilbanks GD, Persky V, Lurain JR (1996) Case-control study of endogenous steroid hormones and endometrial cancer. J Natl Cancer Inst 88:1127–1135PubMed

65.

Riben MW, Malfetano JH, Nazeer T, Muraca PJ, Ambros RA, Ross JS (1997) Identification of HER-2/neu oncogene amplification by fluorescence in situ hybridization in stage I endometrial carcinoma. Mod Pathol 10:823–831PubMed

66.

Riethdorf L, Begemann C, Riethdorf S, Milde-Langosch K, Loning T (1996) Comparison of benign and malignant endometrial lesions for their p53 state, using immunohistochemistry and temperature-gradient gel electrophoresis. Virchows Arch 428:47–51PubMed

67.

Risinger JI, Dent GA, Ignar-Trowbridge D, McLachlan JA, Tsao MS, Senterman M, Boyd J (1992) p53 gene mutations in human endometrial carcinoma. Mol Carcinog 5:250–253PubMed

68.

Risinger JI, Berchuck A, Kohler MF, Watson P, Lynch HT, Boyd J (1993) Genetic instability of microsatellites in endometrial carcinoma. Cancer Res 53:5100–5103PubMed

69.

Risinger JI, Umar A, Boyd J, Berchuck A, Kunkel TA, Barrett JC (1996) Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair. Nat Genet 14:102–105PubMed

70.

Risinger JI, Hayes K, Maxwell GL, Carney ME, Dodge RK, Barrett JC, Berchuck A (1998) PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics. Clin Cancer Res 4:3005–3010PubMed

71.

Risinger JI, Maxwell GL, Chandramouli GV, Jazaeri A, Aprelikova O, Patterson T, Berchuck A, Barrett JC (2003) Microarray analysis reveals distinct gene expression profiles among different histologic types of endometrial cancer. Cancer Res 63:6–11PubMed

72.

Rolitsky CD, Theil KS, McGaughy VR, Copeland LJ, Niemann TH (1999) HER-2/neu amplification and overexpression in endometrial carcinoma. Int J Gynecol Pathol 18:138–143

73.

Ronnett BM, Burks RT, Cho KR, Hedrick L (1997) DCC genetic alterations and expression in endometrial carcinoma. Mod Pathol 10:38–46PubMed

74.

Saegusa M, Hashimura M, Yoshida T, Okayasu I (2001) Beta-catenin mutations and aberrant nuclear expression during endometrial tumorigenesis. Br J Cancer 84:209–217CrossRefPubMed

75.

Saffari B, Jones LA, el-Naggar A, Felix JC, George J, Press MF (1995) Amplification and overexpression of HER-2/neu (c-erbB2) in endometrial cancers: correlation with overall survival. Cancer Res 55:5693–5698PubMed

76.

Saito T, Nishimura M, Yamasaki H, Kudo R (2003) Hypermethylation in promoter region of E-cadherin gene is associated with tumor dedifferention and myometrial invasion in endometrial carcinoma. Cancer 97:1002–1009CrossRefPubMed

77.

Salvesen HB, Das S, Akslen LA (2000) Loss of nuclear p16 protein expression is not associated with promoter methylation but defines a subgroup of aggressive endometrial carcinomas with poor prognosis. Clin Cancer Res 6:153–159PubMed

78.

Salvesen HB, MacDonald N, Ryan A, Iversen OE, Jacobs IJ, Akslen LA, Das S (2000) Methylation of hMLH1 in a population-based series of endometrial carcinomas. Clin Cancer Res 6:3607–3613PubMed

79.

Salvesen HB, MacDonald N, Ryan A, Jacobs IJ, Lynch ED, Akslen LA, Das S (2001) PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma. Int J Cancer 91:22–26CrossRefPubMed

80.

Schlosshauer PW, Ellenson LH, Soslow RA (2002) Beta-catenin and E-cadherin expression patterns in high-grade endometrial carcinoma are associated with histological subtype. Mod Pathol 15:1032–1037PubMed

81.

Schweizer P, Moisio AL, Kuismanen SA, Truninger K, Vierumaki R, Salovaara R, Arola J, Butzow R, Jiricny J, Peltomaki P, Nystrom-Lahti M (2001) Lack of MSH2 and MSH6 characterizes endometrial but not colon carcinomas in hereditary nonpolyposis colorectal cancer. Cancer Res 61:2813–2815PubMed

82.

Semczuk A, Schneider-Stock R, Berbec H, Marzec B, Jakowicki JA, Roessner A (2001) K-ras exon 2 point mutations in human endometrial cancer. Cancer Lett 164:207–212PubMed

83.

Semczuk A, Marzec B, Roessner A, Jakowicki JA, Wojcierowski J, Schneider-Stock R (2002) Loss of heterozygosity of the retinoblastoma gene is correlated with the altered pRb expression in human endometrial cancer. Virchows Arch 441:577–583CrossRefPubMed

84.

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

85.

Sherman ME, Sturgeon S, Brinton LA, Potischman N, Kurman RJ, Berman ML, Mortel R, Twiggs LB, Barrett RJ, Wilbanks GD (1997) Risk factors and hormone levels in patients with serous and endometrioid uterine carcinomas. Mod Pathol 10:963–968PubMed

86.

Shiozawa T, Nikaido T, Shimizu M, Zhai Y, Fujii S (1997) Immunohistochemical analysis of the expression of cdk4 and p16INK4 in human endometrioid-type endometrial carcinoma. Cancer 80:2250–2256CrossRefPubMed

87.

Simpkins SB, Bocker T, Swisher EM, Mutch DG, Gersell DJ, Kovatich AJ, Palazzo JP, Fishel R, Goodfellow PJ (1999) MLH1 promoter methylation and gene silencing is the primary cause of microsatellite instability in sporadic endometrial cancers. Hum Mol Genet 8:661–666CrossRefPubMed

88.

Sonoda G, du Manoir S, Godwin AK, Bell DW, Liu Z, Hogan M, Yakushiji M, Testa JR (1997) Detection of DNA gains and losses in primary endometrial carcinomas by comparative genomic hybridization. Genes Chromosomes Cancer 18:115–125PubMed

89.

Soslow RA, Pirog E, Isacson C (2000) Endometrial intraepithelial carcinoma with associated peritoneal carcinomatosis. Am J Surg Pathol 24:726–732CrossRefPubMed

90.

Staebler A, Lax SF, Ellenson LH (2000) Altered expression of hMLH1 and hMSH2 protein in endometrial carcinomas with microsatellite instability. Hum Pathol 31:354–358PubMed

91.

Stefansson I, Akslen LA, MacDonald N, Ryan A, Das S, Jacobs IJ, Salvesen HB (2002) Loss of hMSH2 and hMSH6 expression is frequent in sporadic endometrial carcinomas with microsatellite instability: a population-based study. Clin Cancer Res 8:138–143PubMed

92.

Stewart RL, Royds JA, Burton JL, Heatley MK, Wells M (1998) Direct sequencing of the p53 gene shows absence of mutations in endometrioid endometrial adenocarcinomas expressing p53 protein. Histopathology 33:440–445CrossRefPubMed

93.

Suehiro Y, Umayahara K, Ogata H, Numa F, Yamashita Y, Oga A, Morioka H, Ito T, Kato H, Sasaki K (2000) Genetic aberrations detected by comparative genomic hybridization predict outcome in patients with endometrioid carcinoma. Genes Chromosomes Cancer 29:75–82CrossRefPubMed

94.

Sumoi R, Hakala Ala Pietila T, Leminen A, Mecklin JP, Lehtovirta P (1995) Hereditary aspects of endometrial adenocarcinoma. Int J Cancer 62:132–137

95.

Sun H, Enomoto T, Shroyer KR, Ozaki K, Fujita M, Ueda Y, Nakashima R, Kuragaki C, Ueda G, Murata Y (2002) Clonal analysis and mutations in the PTEN and the K-ras genes in endometrial hyperplasia. Diagn Mol Pathol 11:204–211CrossRefPubMed

96.

Tashiro H, Blazes MS, Wu R, Cho KR, Bose S, Wang SI, Li J, Parsons R, Ellenson LH (1997) Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res 57:3935–3940PubMed

97.

Tashiro H, Isacson C, Levine R, Kurman RJ, Cho KR, Hedrick L (1997) p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis. Am J Pathol 150:177–185PubMed

98.

Tashiro H, Lax SF, Gaudin PB, Isacson C, Cho KR, Hedrick L (1997) Microsatellite instability is uncommon in uterine serous carcinoma. Am J Pathol 150:75–79PubMed

99.

Tavassoli FA, Devilee P (eds) (2003) Tumours of the breast and female genital organs. IARC Press, Lyon

100.

Tsuda H, Yamamoto K, Inoue T, Uchiyama I, Umesaki N (2000) The role of p16-cyclin d/CDK-pRb pathway in the tumorigenesis of endometrioid-type endometrial carcinoma. Br J Cancer 82:675–682CrossRefPubMed

101.

Vasen HF, Watson P, Mecklin JP, Jass JR, Green JS, Nomizu T, Muller H, Lynch HT (1994) The epidemiology of endometrial cancer in hereditary nonpolyposis colorectal cancer. Anticancer Res 14:1675–1678PubMed

102.

Wada H, Enomoto T, Fujita M, Yoshino K, Nakashima R, Kurachi H, Haba T, Wakasa K, Shroyer KR, Tsujimoto M, Hongyo T, Nomura T, Murata Y (1997) Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors. Cancer Res 57:5379–5385PubMed

103.

Watson P, Vasen HF, Mecklin JP, Jarvinen H, Lynch HT (1994) The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer. Am J Med 96:516–520PubMed

104.

Weiderpass E, Adami HO, Baron JA, Magnusson C, Bergstrom R, Lindgren A, Correia N, Persson I (1999) Risk of endometrial cancer following estrogen replacement with and without progestins. J Natl Cancer Inst 91:1131–1137PubMed

105.

Wheeler DT, Bell KA, Kurman RJ, Sherman ME (2000) Minimal uterine serous carcinoma: diagnosis and clinicopathologic correlation. Am J Surg Pathol 24:797–806CrossRefPubMed

106.

Wijnen JT, Vasen HF, Khan PM, Zwinderman AH, van der Klift H, Mulder A, Tops C, Moller P, Fodde R (1998) Clinical findings with implications for genetic testing in families with clustering of colorectal cancer. N Engl J Med 339:511–518PubMed

107.

Williams JA Jr, Wang ZR, Parrish RS, Hazlett LJ, Smith ST, Young SR (1999) Fluorescence in situ hybridization analysis of HER-2/neu, c-myc, and p53 in endometrial cancer. Exp Mol Pathol 67:135–143CrossRefPubMed

108.

Zhou XP, Kuismanen S, Nystrom-Lahti M, Peltomaki P, Eng C (2002) Distinct PTEN mutational spectra in hereditary non-polyposis colon cancer syndrome-related endometrial carcinomas compared to sporadic microsatellite unstable tumors. Hum Mol Genet 11:445–450CrossRefPubMed

Title: Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification
Author: Sigurd F. Lax
Publication date: 01-03-2004
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 3/2004
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-003-0947-3

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Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification

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