Advertisement

Molekulare Pathogenese der Malignome des Genitalbereichs

  • Magnus von Knebel Doeberitz
Chapter
Part of the Molekulare Medizin book series (MOLMED)

Zusammenfassung

Tumoren des weiblichen Genitaltrakts weisen besondere epidemiologische Verteilungsmuster auf, die für die onkologische Ursachen- und Grundlagenforschung in den letzten Jahrzehnten richtungsweisende Einsichten und Erkenntnisse ergeben haben. Zum einen finden sich bestimmte erbliche Verteilungs muster insbesondere beim Endometrium- und Ovarialkarzinom, die nahe legten, dass erbliche Prädispositionen in der Pathogenese dieser Tumoren eine wesentliche Rolle spielen. Durch diese Beobachtungen konnten u. a. die zentrale Rolle so wesentlicher Tumorsuppressorgene wie der Brust- und Ovarialkrebsgene BRCA1 und BRCA2, aber auch der DNA-Mismatch-Reparaturgene hMLH1, hMSH2 und hMLH6 beim hereditären Endometriumkarzinom charakterisiert werden. Andererseits fanden sich gerade beim Zervixkarzinom, aber auch dem Vulva- und Vaginalkarzinom epidemiologische Anhaltspunkte für einen sexuell übertragbaren Erreger, die letztendlich zur Entdeckung und Charakterisierung der onkogenen humanen Papillomviren geführt haben.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. Abulafia O, Sherer DM (1999) Automated cervical cytology:meta-analyses of the performance of the AutoPap 300 QC system. Obstet Gynecol Surv 54:469–476PubMedGoogle Scholar
  2. Angioli R, Estape R, Mason M, Penalver M (1998) Hereditary and sporadic ovarian cancer: genetic testing and clinical implications. Int J Oncol 12:1029–1034PubMedGoogle Scholar
  3. Anttila A, Pukkala E, Soderman B, Kallio M, Nieminen P, Hakama M (1999) Effect of organised screening on cervical cancer incidence and mortality in Finland, 1963-1995: recent increase in cervical cancer incidence. Int J Cancer 83:59–65PubMedGoogle Scholar
  4. Arzimanoglou II, Lallas T, Osborne M, Barber H, Gilbert F (1996) Microsatellite instability differences between familial and sporadic ovarian cancers. Carcinogenesis 17:1799–1804PubMedGoogle Scholar
  5. Arzimanoglou II, Gilbert F, Barber H.R. (1998) Microsatellite instability in human solid tumors. Cancer 82:1808–1820PubMedGoogle Scholar
  6. Berchuck A, Schildkraut J (1997) Oral contraceptive pills. Prevention of ovarian cancer and other benefits. NC Med J 58:404–407Google Scholar
  7. Boland CR, Thibodeau SN, Hamilton SR et al.(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 58:5248–5257PubMedGoogle Scholar
  8. Boyd J (1998) Molecular genetics of hereditary ovarian cancer. Oncology (Huntingt) 12:399–406Google Scholar
  9. Boyd J, Sonoda Y, Federici MG et al. (2000) Clinicopathologic features of BRCA-linked and sporadic ovarian cancer.JAMA 283:2260–2265PubMedGoogle Scholar
  10. Bulun SE, Economos K, Miller D, Simpson ER (1994) CYP1 (arornatase cytochrome P450) gene expression in human malignant endometrial tumors. J Clin Endocrinol Metab 79:1831–1834PubMedGoogle Scholar
  11. Burke TW, Heller PB, Woodward JE, Davidson SA, Hoskins WJ, Park RC (1990) Treatment failure in endometrial carcinoma.Obstet Gynecol 75:96–101PubMedGoogle Scholar
  12. Burks RT, Kessis TD, Cho KR, Hedrick L (1994) Microsatellite instability in endometrial carcinoma. Oncogene9:1163–1166PubMedGoogle Scholar
  13. Caduff RF, Johnston CM, Frank TS (1995) Mutations of the Ki-ras oncogene in carcinoma of the endometrium. Am J Pathol 146:182–188PubMedCentralPubMedGoogle Scholar
  14. Casey G (1997) The BRCA1 and BRCA2 breast cancer genes.Curr Opin Oncol 9:88–93PubMedGoogle Scholar
  15. Cenci M, Nagar C, Giovagnoli MR, Vecchione A (1997) The PAPNET system for quality control of cervical smears: validation and limits. Anticancer Res 17:4731–4734PubMedGoogle Scholar
  16. Chen NJ, Okuda H, Sekiba K (1985) Recurrent carcinoma of the vagina following Okabayashi’s radical hysterectomy for cervical carcinoma. Gynecol Oncol 20:10–16PubMedGoogle Scholar
  17. Cuzick J, Meijer CJ, Walboomers JM (1998) Screening for cervical cancer. Lancet 351:1439–1440PubMedGoogle Scholar
  18. De Vet HC, Knipschild PG, Schouten HJ et al. (1990) Interobserver variation in histopathological grading of cervical dysplasia. J Clin Epidemiol 43:1395–1398PubMedGoogle Scholar
  19. De Vet HC, Knipschild PG, Schouten HJ et al. (1992) Sources of interobserver variation in histopathological grading of cervical dysplasia. J Clin Epidemiol 45:785–790PubMedGoogle Scholar
  20. Dunlop MG, Farrington SM, Carothers AD et al. (1997) Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet 6:105–110PubMedGoogle Scholar
  21. Easton DF, Ford D, Bishop DT (1995) Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 56:265–271PubMedCentralPubMedGoogle Scholar
  22. Ellenson LH (2000) The molecular biology of endometrial tumorigenesis: does it have a message? Int J Gynecol Pathol 19:310–313PubMedGoogle Scholar
  23. 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 17:2413–2417PubMedGoogle Scholar
  24. Farghaly SA (1998) BRCA1 and BRCA2 gene mutations in hereditary and sporadic ovarian cancer and the clinical implications. Am J Obstet Gynecol 179:1101–1102PubMedGoogle Scholar
  25. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE (1994) Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 343:692–695PubMedGoogle Scholar
  26. Ford D, Easton DF, Stratton M et al. (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 62:676–689PubMedCentralPubMedGoogle Scholar
  27. Foulkes WD, Narod SA (1995) Hereditary breast and ovarian cancer: epidemiology, genetics, screening and predictive testing. Clin Invest Med 18:473–483PubMedGoogle Scholar
  28. Gallion HH, Pieretti M, DePriest PD, Nagell JR van (1995) The molecular basis of ovarian cancer. Cancer 76:1992–1997PubMedGoogle Scholar
  29. Gissmann L, Boshart M, Durst M, Ikenberg H, Wagner D, zur Hausen H (1984) Presence of human papillomavirus in genital tumors. J luvest Dermatol 83:26s–28sGoogle Scholar
  30. Gnagy S, Ming EE, Devesa SS, Hartge P, Whittemore AS (2000) Dedining ovarian cancer rates in US women in relation to parity and oral contraceptive use. Epidemiology 11:102–105PubMedGoogle Scholar
  31. Gore H (1994) Histopathology of ovarian cancer. Semin Surg Oncol 10:255–260PubMedGoogle Scholar
  32. Halford JA, Wright RG, Ditchmen EJ (1999) Prospective study of PAPNET: review of 25,656 Pap smears negative on manual screening and rapid re screening. Cytopathology10:317–323PubMedGoogle Scholar
  33. Han R, Cladel NM, Reed CA, Peng X, Christensen ND (1999) Protection of rabbits from viral challenge by gene gun-based intracutaneous vaccination with a combination of cottontail rabbit papillomavirus E1, E2, E6, and E7 genes. J Virol 73:7039–7043PubMedCentralPubMedGoogle Scholar
  34. Herman JG, Umar A, Polyak K et al. (1998) Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci USA 95:6870–6875PubMedCentralPubMedGoogle Scholar
  35. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD (1998) Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 338:423–428PubMedGoogle Scholar
  36. Hoffmann JS, Cazaux C (1998) DNA synthesis, mismatch repair and cancer. Int J Oncol 12:377–382PubMedGoogle Scholar
  37. Holowaty P, Miller AB, Rohan T, To T (1999) Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst 91:252–258PubMedGoogle Scholar
  38. Holschneider CH, Berek JS (2000) Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol 19: 3–10PubMedGoogle Scholar
  39. Hopfl R, Heim K, Christensen N et al. (2000) Spontaneous regression of CIN and delayed-type hypersensitivity to HPV-16 oncoprotein E7. Lancet 356:1985–1986PubMedGoogle Scholar
  40. Jansen KU, Rosolowsky M, Schultz LD et al. (1995) Vaccination with yeast-expressed cottontail rabbit papillomavirus (CRPV) virus-like particles protects rabbits from CRPVinduced papilloma formation. Vaccine 13:1509–1514PubMedGoogle Scholar
  41. Jeon S, Lambert PF (1995) Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis. Proc Natl Acad Sci USA 92:1654–1658PubMedCentralPubMedGoogle Scholar
  42. Jeon S, Allen-Hoffmann BL, Lambert PF (1995) Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol 69:2989–2997PubMedCentralPubMedGoogle Scholar
  43. Jochmus I, Schafer K, Faath S, Muller M, Gissmann L (1999) Chimeric virus-like particles of the human papillomavirus type 16 (HPV 16) as a prophylactic and therapeutic vaccine. Arch Med Res 30:269–274PubMedGoogle Scholar
  44. Kirnbauer R (1996) Papillomavirus-like particles for serology and vaccine development. Intervirology 39:54–61PubMedGoogle Scholar
  45. Kiviat NB, Koutsky LA, Paavonen JA et al. (1989) Prevalence of genital papillomavirus infection among women attending a college student health clinic or a sexually transmitted disease clinic. J Infect Dis 159:293–302PubMedGoogle Scholar
  46. Klaes R, Woerner SM, Ridder R et al. (1999) Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transeripts derived from integrated papillomavirus oncogenes. Cancer Res 59:6132–6136PubMedGoogle Scholar
  47. Klaes R, Friedrich T, Spitkovsky D et al. (2001) Overexpression of p16INK4a as specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer 92:276–284PubMedGoogle Scholar
  48. Knebel DM von (1992a) Papillomaviruses in human disease: Part I. Pathogenesis and epidemiology of human papillomavirus infections. Eur J Med 1:415–423Google Scholar
  49. Knebel DM von (1992b) Papillomaviruses in human disease: Part 11.Molecular biology and immunology of papillomavirus infections and careinogenesis. Eur J Med 1:485–491Google Scholar
  50. Knebel DM von, Gissmann L (1987) Analysis of the biological role of human papilloma virus (HPV)-encoded transcripts in cervical carcinoma cells by antisense RNA. Hamatol Bluttransfus 31:377–379Google Scholar
  51. Knebel DM von, Oltersdorf T, Schwarz E, Gissmann L (1988) Correlation of modified human papilloma virus early gene expression with altered growth properties in C4-1 cervical carcinoma cells. Cancer Res 48:3780–3786Google Scholar
  52. Knebel DM von, Bauknecht T, Bartsch D, zur Hausen H (1991) Influence of chromosomal integration on glucocorticoid-regulated transcription of growth-stimulating papillomavirus genes E6 and E7 in cervical carcinoma cells. Proc Natl Acad Sci USA 88:1411–1415Google Scholar
  53. Knebel DM von, Rittmuller C, zur Hausen H, Durst M (1992) Inhibition of tumorigenicity of cervical cancer cells in nude mice by HPV E6-E7 anti-sense RNA. Int J Cancer 51:831–834Google Scholar
  54. Knebel Doeberitz M von, Rittmüller C, Aengenyndt F, Jansen-Dürr P, Spitkovsky D (1994) Reversible repression of papillomavirus oncoproteins in cervical carcinoma cells: consequences for the phenotype and p53 and pRB interactions. J Virol 68:2811–2821Google Scholar
  55. Kong D, Suzuki A, Zou TT et al. (1997)PTEN1 is frequently mutated in primary endometrial careinomas. Nat Genet 17:143–144PubMedGoogle Scholar
  56. Kovalev S, Marchenko ND, Gugliotta BG, Chalas E, Chumas J, Moll UM (1998) Loss of p53 function in uterine papillary serous carcinoma. Hum Pathol 29:613–619PubMedGoogle Scholar
  57. Launonen V, Mannermaa A, Stenback F et al. (2000) Loss of heterozygosity at chromosomes 3, 6, 8, 11, 16, and 17 in ovarian cancer: correlation to clinicopathological variables. Cancer Genet Cytogenet 122:49–54PubMedGoogle Scholar
  58. Lax SF, Kurman RJ (1997) A dualistic model for endometrial carcinogenesis based on immunohistochemical and molecular genetic analyses. Verh Dtsch Ges Pathol 81:228–232PubMedGoogle Scholar
  59. Leigh IM, Buchanan JA, Harwood CA, Cerio R, Storey A (1999) Role of human papillomaviruses in cutaneous and oral manifestations of immunosuppression. J Acquir Immune Defic Syndr Hum Retrovirol [Suppl 1] 21:S49–S57Google Scholar
  60. Lengauer C, Kinzier KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396:643–649PubMedGoogle Scholar
  61. Levenson AS, Jordan VC (1998) The key to the antiestrogenic mechanism of raloxifene is amino acid 351 (aspartate) in the estrogen receptor. Cancer Res 58:1872–1875PubMedGoogle Scholar
  62. Levine RL, Cargile CB, Blazes MS, Rees B van, Kurman RJ, Ellenson LH (1998) PTEN mutations and microsatellite instability in complex atypical hyperplasia, aprecursor lesion to uterine endometrioid carcinoma. Cancer Res 58:3254–3258PubMedGoogle Scholar
  63. Lin YL, Borenstein LA, Ahmed R, Wettstein FO (1993) Cottontail rabbit papillomavirus LI protein-based vaceines: protection is achieved only with a full-length, nondenatured product. J Virol 67:4154–4162PubMedCentralPubMedGoogle Scholar
  64. Lowy DR, Schiller JT (1999) Papillomaviruses: prophylactic vaccine prospects. Biochim Biophys Acta 1423:M1–M8PubMedGoogle Scholar
  65. Luft F, Gebert J, Schneider A, Melsheimer P, Knebel DM von (1999) Frequent allelic imbalance of tumor suppressor gene loci in cervical dysplasia. Int J Gynecol Pathol 18:374–380PubMedGoogle Scholar
  66. Lynch HT, de la Chapelle CA (1999) Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 36:801–818PubMedCentralPubMedGoogle Scholar
  67. Mann GB, Borgen P.I. (1998) Breast cancer genes and the surgeon. J Surg Oncol 67:267–274PubMedGoogle Scholar
  68. Marcus VA, Madlensky L, Gryfe R et al. (1999) Immunohistochemistry for hMLH1 and hMSH2: a practical test for DNA mismatch repair-deficient tumors. Am J Surg Pathol 23:1248–1255PubMedGoogle Scholar
  69. Marsden DE, Friedlander M, Hacker NMF (2000) Current management of epithelial ovarian carcinoma: a review. Semin Surg Oncol 19:11–19PubMedGoogle Scholar
  70. Melbye M, Sprogel P (1991) Actiological parallel between anal cancer and cervical cancer. Lancet 338:657–659PubMedGoogle Scholar
  71. Mutter GL, Lin MC, Fitzgerald JT et al. (2000) Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 92:924–930PubMedGoogle Scholar
  72. Myers MP, Pass I, Batty IH et al. (1998) The lipid phosphatase activity of PTEN is critical for its tumor suppressor function. Proc Natl Acad Sci USA 95:13513–13518PubMedCentralPubMedGoogle Scholar
  73. Nieminen P, Kallio M, Anttila A, Hakama M (1999) Organised vs. spontaneous Pap-smear screening for cervical cancer: a case-control study. Int J Cancer 83:55–58PubMedGoogle Scholar
  74. Osen W, Jochmus I, Muller M, Gissmann L (2000) Immunization against human papillomavirus infection and associated eoplasia. J Clin Virol 19:75–78PubMedGoogle Scholar
  75. Ostor AG (1993) Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol 12:186–192PubMedGoogle Scholar
  76. O’Suilivan JP (1998) Observer variation in gynaecological cytopathology. Cytopathology 9:6–14Google Scholar
  77. O’Sullivan JP, Ismail SM, Barnes WS et al. (1994) Interobserver variation in the diagnosis and grading of dyskaryosis in cervical smears: specialist cytopathologists compared with non-specialists. J Clin Pathol 47:515–518Google Scholar
  78. Pagano M, Durst M, Joswig S, Draetta G, Jansen-Durr P (1992) Binding of the human E2F transcription factor to the retinoblastoma protein but not to cyclin A is abolished in HPV-16-immortalized cells. Oncogene 7:1681–1686PubMedGoogle Scholar
  79. Papanicolaou GN, Traut HF (1997) The diagnostic value of vaginal smears in carcinoma of the uterus. Arch Pathol Lab Med 121:211–224PubMedGoogle Scholar
  80. Parkin DM, Pisani P, Ferlay J (1999) Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 80:827–841PubMedGoogle Scholar
  81. Perego P, Giarola M, Righetti SC et al. (1996) Association between cisplatin resistance and mutation of p53 gene and reduced bax expression in ovarian carcinoma cell systems. Cancer Res 56:556–562PubMedGoogle Scholar
  82. Petry KU, Bohmer G, Iftner T, Flemming P, Stoll M, Schmidt RE (1999) Human papillomavirus testing in primary screening for cervical cancer of human immunodeficiency virus-infected women, 1990-1998. Gynecol Oncol 75:427–431Google Scholar
  83. Planck M, Wenngren E, Borg A, Olsson H, Nilbert M (2000) Somatic frameshift alterations in mononucleotide repeatcontaining genes in different tumor types from an HNPCC family with germline MSH2 mutation. Genes Chromosomes Cancer 29:33–39PubMedGoogle Scholar
  84. Reuter S, Bartelmann M, Vogt M et al. (1998) APM-1, a novel human gene, identified by aberrant co-transcription with papillomavirus oncogenes in a cervical carcinoma cell line, encodes a BTB/POZ-zinc finger protein with growth inhibitory activity. EMBO J 17:215–222PubMedCentralPubMedGoogle Scholar
  85. Risinger JI, Berchuck A, Kohler MF, Watson P, Lynch HT, Boyd J (1993) Genetic instability of microsatellites in endometrial carcinoma. Cancer Res 53:5100–5103PubMedGoogle Scholar
  86. Risinger JI, Umar A, Boyer JC et al. (1995) Microsatellite instability in gynecological sarcomas and in hMSH2 mutant uterine sarcoma cell lines defective in mismatch repair activity. Cancer Res 55:5664-5669Google Scholar
  87. Risinger JI, Hayes AK, Berchuck A, Barrett JC (1997) PTEN/MMACI mutations in endometrial cancers. Cancer Res 57:4736–4738PubMedGoogle Scholar
  88. Risinger JI, Hayes K, Maxwell GL et al. (1998) PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics. Clin Cancer Res 4:3005–3010PubMedGoogle Scholar
  89. Saffari B, Jones LA, Naggar A el, Felix JC, George J, Press MF (1995) Amplification and overexpression of HER-21 neu (c-erbB2) in endometrial cancers: correlation with overall survival. Cancer Res 55:5693–5698PubMedGoogle Scholar
  90. Sano T, Oyama T, Kashiwabara K, Fukuda T, Nakajima T (1998) Expression status of p 16 protein is associated with human papillomavirus oncogenic potential in cervical and genitallesions. Am J Pathol 153:1741–1748PubMedCentralPubMedGoogle Scholar
  91. Scheffner M, Huibregtse JM, Vierstra RD, Howley PM (1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75:495–505PubMedGoogle Scholar
  92. Scully RE (1975) World Health Organization classification and nomenclature of ovarian cancer. Natl Cancer lust Monogr 42:5–7Google Scholar
  93. Segnan N (1994) Cervical cancer screening. Human benefits and human costs in the evaluation of screening programmes. Eur J Cancer 30A:873–875PubMedGoogle Scholar
  94. Selvakumar R, Borenstein LA, Lin YL, Ahmed R, Wettstein FO (1995) Immunization with nonstructural proteins E1 and E2 of cottontail rabbit papillomavirus stimulates regression of virus-induced papillomas. J Virol 69:602–605PubMedCentralPubMedGoogle Scholar
  95. Shattuck-Eidens D, McClure M, Simard J et al. (1995) A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening. JAMA 273:535–541PubMedGoogle Scholar
  96. Sherman ME (2000) Theories of endometrial carcinogenesis: a multidisciplinary approach. Mod Pathol 13:295–308PubMedGoogle Scholar
  97. Sherman ME, Schiffman M, Herrero R et al. (1998) Performance of a semiautomated Papanicolaou smear screening system: results of a population-based study conducted in Guanacaste, Costa Rica. Cancer 84:273–280PubMedGoogle Scholar
  98. Simpkins SB, Bocker T, Swisher EM et al. (1999) MLH1 promoter methylation and gene silencing is the primary cause of microsatellite instability in sporadic endometrial cancers. Hum Mol Genet 8:661–666PubMedGoogle Scholar
  99. Sirchia SM, Sironi E, Grati FR et al. (2000) Losses of heterozygosity in endometrial adenocarcinomas: positive correlations with histopathological parameters. Cancer Genet Cytogenet 121:156–162PubMedGoogle Scholar
  100. Smith LH, Oi RH (1984) Detection of malignant ovarian neoplasms: a review of the literature. I. Detection of the patient at risk; clinical, radiological and cytological detection. Obstet Gynecol Surv 39:313–328PubMedGoogle Scholar
  101. Soler ME, Blumenthai PD (2000) New technologies in cervical cancer precursor detection. Curr Opin Oncol 12:460–465PubMedGoogle Scholar
  102. Solomon D, Schiffman M, Tarone R (2001) Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer lust 93:293–299Google Scholar
  103. Sutcliffe S, Pharoah PD, Easton DF, Ponder BA (2000) Ovarian and breast cancer risks to women in families with two or more cases of ovarian cancer. Int J Cancer87:110–117PubMedGoogle Scholar
  104. Suzich JA, Ghim SJ, Palmer-Hill FJ et al. (1995) Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas. Proc Natl Acad Sci USA 92:11553–11557PubMedCentralPubMedGoogle Scholar
  105. Tashiro H, Blazes MS, Wu R et al. (1997) Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res 57:3935–3940PubMedGoogle Scholar
  106. Taylor MR (2001) Genetic testing for inherited breast and ovarian cancer syndromes: important concepts for the primary care physician. Postgrad Med J 77:11–15PubMedCentralPubMedGoogle Scholar
  107. Tritz D, Pieretti M, Turner S, Powell D (1997) Loss of heterozygosity in usual and special variant carcinomas of the endometrium. Hum Pathol 28:607–612PubMedGoogle Scholar
  108. Viikki M, Pukkala E, Hakama M (1998) Risk of endometrial, ovarian, vulvar, and vaginal cancers after a positive cervical cytology followed by negative histology. Obstet Gynecol 92:269–273PubMedGoogle Scholar
  109. Walboomers JM, Jacobs MV, Manos MM et al. (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19PubMedGoogle Scholar
  110. Yamada H, Sasaki M, Honda T et al. (1995) Suppression of endometrial carcinoma cell tumorigenicity by human chromosome 18. Genes Chromosomes Cancer 13:18–24PubMedGoogle Scholar
  111. Yang X, Lippman ME (1999) BRCA1 and BRCA2 in breast cancer. Breast Cancer Res Treat 54:1–10PubMedGoogle Scholar
  112. Yokoyama M, Nakao Y, Yang X et al. (1995) Alterations in physical state and expression of human papillomavirus type 18 DNA following crisis and establishment of immortalized ectocervical cells. Virus Res 37:139–151PubMedGoogle Scholar
  113. Zerfass K, Levy LM, Cremonesi C et al. (1995) Cell cycle-dependent disruption of E2F-p107 complexes by human papillomavirus type 16 E7. J Gen Virol 76:1815–1820PubMedGoogle Scholar
  114. Zheng L, Li S, Boyer TG, Lee WH (2000) Lessons learned from BRCAI and BRCA2. Oncogene 19:6159–6175PubMedGoogle Scholar
  115. Zuna RE (1984) The Pap smear revisited. Controversies and recent developments. Postgrad Med 76:36–46PubMedGoogle Scholar
  116. zur Hausen H (1999) Immortalization of human cells and their malignant conversion by high risk human papillomavirus genotypes. Semin Cancer Biol 9:405–411PubMedGoogle Scholar
  117. zur Hausen H (2000) Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 92:690–698PubMedGoogle Scholar
  118. Zweemer RP, Verheijen RH, Menko FH et al. (1999) Differences between hereditary and sporadic ovarian cancer. Eur J Obstet Gynecol Reprod Biol 82:151–153PubMedGoogle Scholar
  119. Zwerschke W, Jansen-Durr P (2000) Cell transformation by the E7 oncoprotein of human papillomavirus type 16: interactions with nuclear and cytoplasmic target proteins. Adv Cancer Res 78:1–29PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • Magnus von Knebel Doeberitz

There are no affiliations available

Personalised recommendations