Riassunto
Il carcinoma ovarico è tra le prime cause di morte per neoplasie ginecologiche, con un rischio cumulativo, nella popolazione generale, di sviluppare la neoplasia nell’arco della vita intorno all’1–1,8% e la sopravvivenza globale a 5 anni delle pazienti intorno al 50%. Oltre il 60% dei tumori ovarici, sia benigni che maligni, origina dall’epitelio di rivestimento dell’ovaio. Attualmente, secondo la classificazione patogenetica, i carcinomi ovarici sono distinti in 2 classi: neoplasie di tipo 1, a basso grado e a lenta progressione e di tipo 2, costituite da carcinomi sierosi ad alto grado e a rapida progressione. Recenti dati mostrano come le forme ad alto grado siano caratterizzate da pattern genetici differenti rispetto a quelle a basso grado, per cui si potrebbe ipotizzare che possano esistere due sedi di origine differenti per queste forme tumorali. Per alcuni istotipi ad alto grado è stato ipotizzato, come possibile precursore, il tessuto epiteliale di rivestimento delle fimbrie. Queste nuove acquisizioni potrebbero aiutare a identificare dei biomarker più affidabili, di quelli attualmente in uso, soprattutto per la diagnosi precoce dei carcinomi ovarici. Le ricerche in questo settore hanno permesso di identificare alcuni marcatori molecolari tra cui l’HE4 da poter affiancare al marcatore Ca125, che, oggi, risulta l’unico raccomandato da associare all’ecografia trans-vaginale per la diagnosi differenziale di una massa pelvica. HE4 sembra essere più sensibile di Ca125 soprattutto negli stadi precoci di malattia e nelle pazienti in età pre- e perimenopausale nelle quali è più arduo differenziare una massa annessiale benigna da una maligna.
Summary
Ovarian cancer is among the most lethal malignant diseases in women who have a lifetime probability of around 1.8%of developing the disease and the 5-year survival rate is near 50%. About 60% of the ovarian lesions derive from the ovarian surface epithelium. Recently, proposals of dividing ovarian carcinoma into two broad categories have been considered: type I, which tends to develop slowly and is a low-grade neoplasm; type II which spreads rapidly and has a higher degree of malignancy. Type I and type II tumors are characterized by distinct gene expression patterns. It may be due to the different histological precursors. In particular, type II tumors might derive from fimbrial epithelium. This new insight may provide a molecular platform for the discovery of new ovarian cancer markers. Several studies underline the high sensitivity of a new marker for ovarian carcinoma: HE4. It seems to be really useful when associated with Ca125 as they distinguish a malignant ovarian lesion from a benign one previously identified by transvaginal ultrasonography, especially in the early stages of the disease and in the pre-menopausal period.
Bibliografia
International Agency for Research on Cancer: Cancer Mondial. http://www-dep.iarc.fr/. Accessed July 8 2011
Drapkin R, Hecht JL (2002) The origins of ovarian cancer: hurdles and progress. Women’2019;s Oncol Rev; 2:261–268
Auersperg N, Wong AS, Choi KC et al (2001) Ovarian surface epithelium: biology, endocrinology and pathology. Endocr Rev 22:255–288
Fleming JS, Beaugie CR, Haviv I et al (2006) Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: revisiting old hypotheses. Mol Cell Endocrinol 247:4–21
Pharoah PD, Ponder BA (2002) The genetics of ovarian cancer. Best Pract Res Clin Obstet Gynaecol 16: 449–468
Ramus SJ, Gayther SA (2009) The contribution of BRCA1 and BRCA2 to ovarian cancer. Mol Oncol 3:138–150
Malander S, Rambech E, Kristoffersson U et al(2006) The contribution of the hereditary nonpolyposis colorectal cancer syndrome to the development of ovarian cancer. Gynecol Oncol 101:238–243
Seidman JD, Horkayne-Szakaly I, Haiba M et al (2004) The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin. Int J Gynecol Pathol 23:41–44
Simpson NK, Johnson CC, Ogden SL et al (2000) Recruitment strategies in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial: the first six years. Control Clin Trials 21:356S–378S
Menon U, Jacobs I (2002) Screening for ovarian cancer. Best Pract Res Clin Obstet Gynaecol 16:469–482
Levanon K, Crum C, Drapkin R (2008) New insights into the pathogenesis of serous ovarian cancer and its clinical impact. J Clin Oncol 26:5284–5293
Levine DA, Boyd J (2001) The androgen receptor and genetic susceptibility to ovarian cancer: results from a case-series. Cancer Res 61:908–911
Narod SA, Risch H, Moslehi R et al (1998) Oral contraceptives and the risk of hereditary ovarian cancer. New Engl J Med 339:424–428
Narod SA, Sun P, Ghadirian P et al (2001) Tubal ligation and risk of ovarian cancer in carriers of BRCA1 orBRCA2 mutations: a case-control study. Lancet 357:1467–1470
Landen CN Jr, Birrer MJ, Sood AK (2008) Early events in the pathogenesis of epithelial ovarian cancer. J Clin Oncol 26:995–1005
Shih IeM, Kurman RJ (2004) Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol 164:1511–1518
Singer G, Oldt R 3rd, Cohen Y et al (2003) Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst 95:484–486
Obata K, Morland SJ, Watson RH, Hitchcock A, Chenevix-Trench G, Thomas EJ, Campbell IG (1998) Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res 58:2095–2097
Wu R, Zhai Y, Fearon ER, Cho KR (2001) Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas. Cancer Res 61:8247–8255
Fathalla MF (1971) Incessant ovulation: a factor in ovarian neoplasia? Lancet 298:163
Drapkin RI, Hecht JL (2006) Pathogenesis of ovarian cancer. PA: WB Saunders, Philadelphia
Kindelberger DW, Lee Y, Miron A, et al (2007) Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol 31:161–169
Bast RC, Brewer M, Zou C et al (2007) Prevention and early detection of ovarian cancer: mission impossible? Recent Results Cancer Res 174:91–100
American College of Physicians (1994) Screening for ovarian cancer: recommendations and rationale. Ann Intern Med 121:141–142
Vasey PA, Herrstedt J, Jelic S (2005) ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of epithelial ovarian carcinoma. Ann Oncol 16 (Suppl 1):i13–i15
National Comprehensive Cancer Network (NCCN) (2005) Clinical Practice Guidelines in Oncology. Ovarian Cancer. Version 1, Vol 1. http://www.nccn.com/images/patient-guidelines/pdf/ovarian.pdf
The National Academy of Clinical Biochemistry (NACB): Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers. http://www. aacc.org /members /nacb/LMPG-/OnlineGuide/PublishedGuidelines/major/Pages/toc.aspx
Bast RC, Jr., Feeney M, Lazarus H et al (1981) Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest 68:1331–1337
Yin BW, Lloyd KO (2001) Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16. J Biol Chem 276:27371–27375
Shih Ie M, Sokoll L, Chan DW (2002) Ovarian cancer. In: Diamandis EP, Fritsche HA, Lilja H, Chan DW, Schwartz MK, edn. Tumor Markers: Physiology, pathobiology, technology and clinical applications. AACC Press, Washington DC, pp 239–252
Muto MG, Cramer DW, Brown DL et al (1993) Screening for ovarian cancer: the preliminary experience of a familial ovarian cancer center. Gynecol Oncol 51:12–20
Oei AL, Massuger LF, Bulten J, Ligtenberg MJ, Hoogerbrugge N, de Hullu JA (2006) Surveillance of women at high risk for hereditary ovarian cancer is inefficient. Br J Cancer 94:814–819
Munkarah A, Chatterjee M, Tainsky MA (2007) Update on ovarian cancer screening. Curr Opin Obstet Gynecol 19:22–26
Jacobs I, Bast RC Jr (1989) The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod 4:1–12
Pauler DK, Menon U, McIntosh M et al (2001) Factors influencing serum CA125II levels in healthy postmenopausal women. Cancer Epidemiol Biomarkers Prev 10:489–493
Bast RC Jr, Xu FJ, Yu YH et al (1998) CA125: the past and the future. Int J Biol Markers 13:179–187
Fleisher M, Dnistrian A, Sturgeon C, Lamerz R, Witliff J (2002) Practice guidelines and recommendations for use of tumor markers in the clinic. Tumor Markers: Physiology, pathobiology, technology and clinical applications, AACC Press, Washington, pp 33–63
Finkler NJ, Benacerraf B, Lavin PT et al (1988) Obstet Comparison of serum CA 125, clinical impression, and ultrasound in the preoperative evaluation of ovarian masses. Gynecol 72:659–664
CA125 definitions agreed by GCIG November 2005 http://ctep.cancer.gov/resources/gcig/respdef.html
Fritsche HA, Bast RC (1998) CA 125 in ovarian cancer: advances and controversy. Clin Chem 44:1379–1380
Meyer T, Rustin GJ (2000) Role of tumour markers in monitoring epithelial ovarian cancer. Br J Cancer 82:1535–1538
Santillan A, Garg R, Zahurak ML et al (2005) Risk of epithelial ovarian cancer recurrence in patients with rising serum CA-125 levels within the normal range. J Clin Oncol 23:9338–9343
Verheijen RH, von Mensdorff-Pouilly S, van Kamp GJ, Kenemans P (1999) CA 125: fundamental and clinical aspects. Semin Cancer Biol 9:117–124
Riedinger JM, Wafflart J, Ricolleau G et al (2006) CA 125 halflife and CA 125 nadir during induction chemotherapy are independent predictors of epithelial ovarian cancer outcome: results of a French multicentric study. Ann Oncol 17:1234–1238
Moore RG, Brown AK, Miller MC et al (2008) The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass Jr Gynecol Oncol. 108:402–40
Huhtinen K, Suvitie P, Hiissa J et al (2009) Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. British J of Cancer 100:1315–1319
Kirchhoff C (1998) Molecular characterization of epididymal proteins. Rev Reprod 3:86–95
Bingle L, Singleton V, Bingle CD (2002) The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms. Oncogene 21:2768–2773
Drapkin R, von Horsten HH, Lin Y et al (2005) Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res 65:2162–2169
Moore RG, Brown AK, Miller MC et al (2008) Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus. Gynecol Oncol 110:196–201
Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG (1990) A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol 97:922–929
Moore RG, McMeekin DS, Brown AK et al (2009) A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol 112:40–46
Moore RG, Jabre-Raughley M, Brown AK et al (2010) Comparison of a novel multiple marker assay vs the Risk of Malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass. Am J Obstet Gynecol 203:228 e1–228 e6
van Nagell JR, Gallion HH, Pavlik EJ, DePriest PD (1995) Ovarian cancer screening. Cancer 76:2086–2091
Bourne TH, Campbell S, Reynolds KM et al (1993) Screening for early familial ovarian cancer with transvaginal ultrasonography and colour blood flow imaging. BMJ 306:1025–1029
Urban N, Drescher C, Etzioni R, Colby C (1997) Use of a stochastic simulation model to identify an efficient protocol for ovarian cancer screening. Control Clin Trials 18:251–270
Menon U, Skates SJ, Lewis S et al (2005) Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer. J Clin Oncol 23:7919–7926
Tailor A, Bourne TH, Campbell S et al (2003) Results from an ultrasound-based familial ovarian cancer screening clinic: a 10-year observational study. Ultrasound Obstet Gynecol 21:378–385
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Orciari, S., Micucci, C., Procopio, A.D. et al. Il carcinoma ovarico: nuove acquisizioni sulla patogenesi e nella diagnostica di laboratorio. Riv Ital Med Lab 7, 195–204 (2011). https://doi.org/10.1007/s13631-011-0028-z
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DOI: https://doi.org/10.1007/s13631-011-0028-z