Molecular biology of gynecological cancer (Review)

Sonoda,Kenzo

doi:10.3892/ol.2015.3862

Molecular biology of gynecological cancer (Review)

Authors:
- Kenzo Sonoda
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Affiliations: Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812‑8582, Japan
Published online on: November 5, 2015 https://doi.org/10.3892/ol.2015.3862
Pages: 16-22

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Abstract

Cancer is a pathological condition in which the balance between cell growth and death is disordered. Various molecules have been reported to be involved in the oncogenic process of invasion, metastasis and resistance to treatment. An exponential growth in the collection of genomic and proteomic data in the past 20 years has provided major advances in understanding the molecular mechanisms of human cancer, which has been applied to diagnostic and treatment strategies. Targeted therapies have been developed and adopted, particularly for advanced, refractory or recurrent cancers, depending on individual molecular profiles. The aim of the present review is to provide a report of the current literature regarding the molecular biology of gynecological cancers.

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1	Hoeijmakers JH: DNA damage, aging, and cancer. N Engl J Med. 361:1475–1485. 2009. View Article : Google Scholar : PubMed/NCBI
2	Entschladen F, Drell TL IV, Lang K, Joseph J and Zaenker KS: Tumour-cell migration, invasion, and metastasis: Navigation by neurotransmitters. Lancet Oncol. 5:254–258. 2004. View Article : Google Scholar : PubMed/NCBI
3	Meacham CE and Morrison SJ: Tumour heterogeneity and cancer cell plasticity. Nature. 501:328–337. 2013. View Article : Google Scholar : PubMed/NCBI
4	Mok TS: Personalized medicine in lung cancer: What we need to know. Nat Rev Clin Oncol. 8:661–668. 2011. View Article : Google Scholar : PubMed/NCBI
5	Diou O, Tsapis N and Fattal E: Targeted nanotheranostics for personalized cancer therapy. Expert Opin Drug Deliv. 9:1475–1487. 2012. View Article : Google Scholar : PubMed/NCBI
6	Croce CM: Oncogenes and cancer. N Engl J Med. 358:502–511. 2008. View Article : Google Scholar : PubMed/NCBI
7	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
8	Esteller M: Epigenetics in cancer. N Engl J Med. 358:1148–1159. 2008. View Article : Google Scholar : PubMed/NCBI
9	Berdasco M and Esteller M: Aberrant epigenetic landscape in cancer: How cellular identity goes awry. Dev Cell. 19:698–711. 2010. View Article : Google Scholar : PubMed/NCBI
10	Esteller M: Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 8:286–298. 2007. View Article : Google Scholar : PubMed/NCBI
11	Jones PA and Baylin SB: The epigenomics of cancer. Cell. 128:683–692. 2007. View Article : Google Scholar : PubMed/NCBI
12	Doroshow JH and Kummar S: Translational research in oncology-10 years of progress and future prospects. Nat Rev Clin Oncol. 11:649–662. 2014. View Article : Google Scholar : PubMed/NCBI
13	Negrini S, Gorgoulis VG and Halazonetis TD: Genomic instability - an evolving hallmark of cancer. Nat Rev Mol Cell Biol. 11:220–228. 2010. View Article : Google Scholar : PubMed/NCBI
14	Tomita N: BCL2 and MYC dual-hit lymphoma/leukemia. J Clin Exp Hematop. 51:7–12. 2011. View Article : Google Scholar : PubMed/NCBI
15	Maire CL and Ligon KL: Molecular pathologic diagnosis of epidermal growth factor receptor. Neuro Oncol. 16:viii1–6. 2014. View Article : Google Scholar : PubMed/NCBI
16	Demoulin JB and Essaghir A: PDGF receptor signaling networks in normal and cancer cells. Cytokine Growth Factor Rev. 25:273–283. 2014. View Article : Google Scholar : PubMed/NCBI
17	Fearon AE, Gould CR and Grose RP: FGFR signaling in women's cancers. Int J Biochem Cell Biol. 45:2832–2842. 2013. View Article : Google Scholar : PubMed/NCBI
18	Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F and Salomon DS: Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 366:2–16. 2006. View Article : Google Scholar : PubMed/NCBI
19	Bishayee A, Beguinot L and Bishayee S: Phosphorylation of tyrosine 992, 1068, and 1086 is required for conformational change of the human epidermal growth factor receptor c-terminal tail. Mol Biol Cell. 10:525–536. 1999. View Article : Google Scholar : PubMed/NCBI
20	Heng BC, Aubel D and Fussenegger M: An overview of the diverse roles of G-protein coupled receptors (GPCRs) in the pathophysiology of various human diseases. Biotechnol Adv. 31:1676–1694. 2013. View Article : Google Scholar : PubMed/NCBI
21	Shaw RJ and Cantley LC: Ras, PI(3)K and mTOR signaling controls tumour cell growth. Nature. 441:424–430. 2006. View Article : Google Scholar : PubMed/NCBI
22	Prior IA, Lewis PD and Mattos C: A comprehensive survey of Ras mutations in cancer. Cancer Res. 72:2457–2467. 2012. View Article : Google Scholar : PubMed/NCBI
23	Fernández-Medarde A and Santos E: Ras in cancer and developmental diseases. Genes Cancer. 2:344–358. 2011. View Article : Google Scholar : PubMed/NCBI
24	Ho CL, Kurman RJ, Dehari R, Wang TL and Shih IeM: Mutations of BRAF and KRAS precede the development of ovarian serous borderline tumors. Cancer Res. 64:6915–6918. 2004. View Article : Google Scholar : PubMed/NCBI
25	Cantwell-Dorris ER, O'Leary JJ and Sheils OM: BRAFV600E: Implications for carcinogenesis and molecular therapy. Mol Cancer Ther. 10:385–394. 2011. View Article : Google Scholar : PubMed/NCBI
26	Eferl R and Wagner EF: AP-1: A double-edged sword in tumorigenesis. Nat Rev Cancer. 3:859–868. 2003. View Article : Google Scholar : PubMed/NCBI
27	Li Y, Casey SC and Felsher DW: Inactivation of MYC reverses tumorigenesis. J Intern Med. 276:52–60. 2014. View Article : Google Scholar : PubMed/NCBI
28	Payne SR and Kemp CJ: Tumor suppressor genetics. Carcinogenesis. 26:2031–2045. 2005. View Article : Google Scholar : PubMed/NCBI
29	Berger AH and Pandolfi PP: Haplo-insufficiency: A driving force in cancer. J Pathol. 223:137–146. 2011. View Article : Google Scholar : PubMed/NCBI
30	Smith U: PTEN - linking metabolism, cell growth, and cancer. N Engl J Med. 367:1061–1063. 2012. View Article : Google Scholar : PubMed/NCBI
31	Chaudru V, Chompret A, Bressac-de Paillerets B, Spatz A, Avril MF and Demenais F: Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by family history and in melanoma-prone families. J Natl Cancer Inst. 96:785–795. 2004. View Article : Google Scholar : PubMed/NCBI
32	Sugimura T and Ushijima T: Genetic and epigenetic alterations in carcinogenesis. Mutat Res. 462:235–246. 2000. View Article : Google Scholar : PubMed/NCBI
33	Greger V, Debus N, Lohmann D, Höpping W, Passarge E and Horsthemke B: Frequency and parental origin of hypermethylated RB1 alleles in retinoblastoma. Hum Genet. 94:491–496. 1994. View Article : Google Scholar : PubMed/NCBI
34	Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S, Samid D, Duan DS, Gnarra JR, Linehan WM, et al: Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA. 91:9700–9704. 1994. View Article : Google Scholar : PubMed/NCBI
35	Dobrovic A and Simpfendorfer D: Methylation of the BRCA1 gene in sporadic breast cancer. Cancer Res. 57:3347–3350. 1997.PubMed/NCBI
36	Arnold CN, Goel A, Niedzwiecki D, Dowell JM, Wasserman L, Compton C, Mayer RJ, Bertagnolli MM and Boland CR: APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q. Cancer Biol Ther. 3:960–964. 2004. View Article : Google Scholar : PubMed/NCBI
37	Madhavan J, Ganesh A and Kumaramanickavel G: Retinoblastoma: From disease to discovery. Ophthalmic Res. 40:221–226. 2008. View Article : Google Scholar : PubMed/NCBI
38	Guimaraes DP and Hainaut P: TP53: A key gene in human cancer. Biochimie. 84:83–93. 2002. View Article : Google Scholar : PubMed/NCBI
39	Lipinski MM and Jacks T: The retinoblastoma gene family in differentiation and development. Oncogene. 18:7873–7882. 1999. View Article : Google Scholar : PubMed/NCBI
40	Soussi T: The history of p53. A perfect example of the drawbacks of scientific paradigms. EMBO Rep. 11:822–826. 2010. View Article : Google Scholar : PubMed/NCBI
41	Ghebranious N and Donehower LA: Mouse models in tumor suppression. Oncogene. 17:3385–3400. 1998. View Article : Google Scholar : PubMed/NCBI
42	Walerych D, Napoli M, Collavin L and Del Sal G: The rebel angel: Mutant p53 as the driving oncogene in breast cancer. Carcinogenesis. 33:2007–2017. 2012. View Article : Google Scholar : PubMed/NCBI
43	Chalhoub N and Baker SJ: PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol. 4:127–150. 2009. View Article : Google Scholar : PubMed/NCBI
44	Jaiswal AS and Narayan S: A novel function of adenomatous polyposis coli (APC) in regulating DNA repair. Cancer Lett. 271:272–280. 2008. View Article : Google Scholar : PubMed/NCBI
45	Tian M and Schiemann WP: The TGF-beta paradox in human cancer: An update. Future Oncol. 5:259–271. 2009. View Article : Google Scholar : PubMed/NCBI
46	Kong YW, Ferland-McCollough D, Jackson TJ and Bushell M: microRNAs in cancer management. Lancet Oncol. 13:e249–258. 2012. View Article : Google Scholar : PubMed/NCBI
47	Lu KH: Hereditary gynecologic cancers: Differential diagnosis, surveillance, management and surgical prophylaxis. Fam Cancer. 7:53–58. 2008. View Article : Google Scholar : PubMed/NCBI
48	Perea J, Rodríguez Y, Rueda D, Marín JC, Díaz-Tasende J, Álvaro E, Alegre C, Osorio I, Colina F, Lomas M, et al: Early-onset colorectal cancer is an easy and effective tool to identify retrospectively Lynch syndrome. Ann Surg Oncol. 18:3285–3291. 2011. View Article : Google Scholar : PubMed/NCBI
49	Nieuwenhuis MH, Kets CM, Murphy-Ryan M, Yntema HG, Evans DG, Colas C, Møller P, Hes FJ, Hodgson SV, Olderode-Berends MJ, et al: Cancer risk and genotype-phenotype correlations in PTEN hamartoma tumor syndrome. Fam Cancer. 13:57–63. 2014. View Article : Google Scholar : PubMed/NCBI
50	Kobayashi H, Ohno S, Sasaki Y and Matsuura M: Hereditary breast and ovarian cancer susceptibility genes (review). Oncol Rep. 30:1019–1029. 2013.PubMed/NCBI
51	Rozen P and Macrae F: Familial adenomatous polyposis: The practical applications of clinical and molecular screening. Fam Cancer. 5:227–235. 2006. View Article : Google Scholar : PubMed/NCBI
52	Vasen HF, Möslein G, Alonso A, et al: Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet. 44:353–362. 2007. View Article : Google Scholar : PubMed/NCBI
53	Harris SL and Levine AJ: The p53 pathway: Positive and negative feedback loops. Oncogene. 24:2899–2908. 2005. View Article : Google Scholar : PubMed/NCBI
54	Collado M and Serrano M: Senescence in tumours: Evidence from mice and humans. Nat Rev Cancer. 10:51–57. 2010. View Article : Google Scholar : PubMed/NCBI
55	Su Z, Yang Z, Xu Y, Chen Y and Yu Q: Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer. 14:482015. View Article : Google Scholar : PubMed/NCBI
56	Hensley P, Mishra M and Kyprianou N: Targeting caspases in cancer therapeutics. Biol Chem. 394:831–843. 2013. View Article : Google Scholar : PubMed/NCBI
57	Lowe SW, Cepero E and Evan G: Intrinsic tumour suppression. Nature. 432:307–315. 2004. View Article : Google Scholar : PubMed/NCBI
58	Van den Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H and Vandenabeele P: Regulated necrosis: The expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol. 15:135–147. 2014. View Article : Google Scholar : PubMed/NCBI
59	Chaabane W, User SD, El-Gazzah M, Jaksik R, Sajjadi E, Rzeszowska-Wolny J and Los MJ: Autophagy, apoptosis, mitoptosis and necrosis: Interdependence between those pathways and effects on cancer. Arch Immunol Ther Exp (Warsz). 61:43–58. 2013. View Article : Google Scholar : PubMed/NCBI
60	van Deursen JM: The role of senescent cells in ageing. Nature. 509:439–446. 2014. View Article : Google Scholar : PubMed/NCBI
61	Sakamoto M, Toyoizumi T, Kikuchi Y, Okamoto A, Nakayama H, Aoki D, Yamamoto K, Hata H, Sugishita T and Tenjin Y: Telomerase activity in gynecological tumors. Oncol Rep. 7:1003–1009. 2000.PubMed/NCBI
62	Nakashima M, Sonoda K and Watanabe T: Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1. Nat Med. 5:938–942. 1999. View Article : Google Scholar : PubMed/NCBI
63	Giaginis C, Giagini A and Theocharis S: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1): A novel biomarker in the diagnosis and prognosis of human neoplasia. Histol Histopathol. 24:761–776. 2009.PubMed/NCBI
64	Sonoda K, Miyamoto S, Hirakawa T, Yagi H, Yotsumoto F, Nakashima M, Watanabe T and Nakano H: Association between RCAS1 expression and microenvironmental immune cell death in uterine cervical cancer. Gynecol Oncol. 97:772–779. 2005. View Article : Google Scholar : PubMed/NCBI
65	Sonoda K: RCAS1 is a promising therapeutic target against cancer: Its multifunctional bioactivities and clinical significance. Expert Rev Obstet Gynecol. 7:261–267. 2012. View Article : Google Scholar
66	Sonoda K, Miyamoto S, Nakashima M and Wake N: The biological role of unique molecule RCAS1: A bioactive marker that induces connective tissue remodeling and lymphocyte apoptosis. Front Biosci. 13:1106–1116. 2008. View Article : Google Scholar : PubMed/NCBI
67	Nishinakagawa T, Fujii S, Nozaki T, Maeda T, Machida K, Enjoji M and Nakashima M: Analysis of cell cycle arrest and apoptosis induced by RCAS1. Int J Mol Med. 25:717–722. 2010.PubMed/NCBI
68	Baeriswyl V and Christofori G: The angiogenic switch in carcinogenesis. Semin Cancer Biol. 19:329–337. 2009. View Article : Google Scholar : PubMed/NCBI
69	Burger RA, Brady MF, Bookman MA, et al: Gynecologic Oncology Group: Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 365:2473–2483. 2011. View Article : Google Scholar : PubMed/NCBI
70	Chéreau E, Lambaudie E and Houvenaeghel G: Morbidity of surgery after neoadjuvant chemotherapy including bevacizumab for advanced ovarian cancer. Int J Gynecol Cancer. 23:1326–1330. 2013. View Article : Google Scholar : PubMed/NCBI
71	Hua H, Li M, Luo T, Yin Y and Jiang Y: Matrix metalloproteinases in tumorigenesis: An evolving paradigm. Cell Mol Life Sci. 68:3853–3868. 2011. View Article : Google Scholar : PubMed/NCBI
72	Planagumà J, Liljeström M, Alameda F, Bützow R, Virtanen I, Reventós J and Hukkanen M: Matrix metalloproteinase-2 and matrix metalloproteinase-9 codistribute with transcription factors RUNX1/AML1 and ETV5/ERM at the invasive front of endometrial and ovarian carcinoma. Hum Pathol. 42:57–67. 2011. View Article : Google Scholar : PubMed/NCBI
73	Yan L, Lin B, Gao L, Gao S, Liu C, Wang C, Wang Y, Zhang S and Iwamori M: Lewis (y) antigen overexpression increases the expression of MMP-2 and MMP-9 and invasion of human ovarian cancer cells. Int J Mol Sci. 11:4441–4452. 2010. View Article : Google Scholar : PubMed/NCBI
74	Kamat AA, Fletcher M, Gruman LM, Mueller P, Lopez A, Landen CN Jr, Han L, Gershenson DM and Sood AK: The clinical relevance of stromal matrix metalloproteinase expression in ovarian cancer. Clin Cancer Res. 12:1707–1714. 2006. View Article : Google Scholar : PubMed/NCBI
75	Sawada K, Mitra AK, Radjabi AR, Bhaskar V, Kistner EO, Tretiakova M, Jagadeeswaran S, Montag A, Becker A, Kenny HA, et al: Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res. 68:2329–2339. 2008. View Article : Google Scholar : PubMed/NCBI
76	Paget S: The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 8:98–101. 1989.PubMed/NCBI
77	Zhang Y, Ma B and Fan Q: Mechanisms of breast cancer bone metastasis. Cancer Lett. 292:1–7. 2010. View Article : Google Scholar : PubMed/NCBI
78	Mukherjee D and Zhao J: The role of chemokine receptor CXCR4 in breast cancer metastasis. Am J Cancer Res. 3:46–57. 2013.PubMed/NCBI
79	Sonoda K: Novel therapeutic strategies to target RCAS1, which induces apoptosis via ectodomain shedding. Histol Histopathol. 26:1475–1486. 2011.PubMed/NCBI
80	Sonoda K, Miyamoto S, Hirakawa T, Yagi H, Yotsumoto F, Nakashima M, Watanabe T and Nakano H: Invasive potency related to RCAS1 expression in uterine cervical cancer. Gynecol Oncol. 99:189–198. 2005. View Article : Google Scholar : PubMed/NCBI
81	Skyldberg B, Salo S, Eriksson E, Aspenblad U, Moberger B, Tryggvason K and Auer G: Laminin-5 as a marker of invasiveness in cervical lesions. J Natl Cancer Inst. 91:1882–1887. 1999. View Article : Google Scholar : PubMed/NCBI
82	Brinkerhoff CE, Rutter JL and Benbow U: Interstitial collagenases as markers of tumor progression. Clin Cancer Res. 6:4823–4830. 2000.PubMed/NCBI
83	Przybylo JA and Radisky DC: Matrix metalloproteinase-induced epithelial-mesenchymal transition: Tumor progression at Snail's pace. Int J Biochem Cell Biol. 39:1082–1088. 2007. View Article : Google Scholar : PubMed/NCBI
84	Sonoda K, Miyamoto S, Kobayashi H, Ogawa S, Okugawa K, Taniguchi S and Wake N: The level of RCAS1 expression is inversely correlated with the number of vimentin-positive stromal cells in epithelial ovarian cancer. Int J Gynecol Cancer. 19:838–843. 2009. View Article : Google Scholar : PubMed/NCBI
85	Byun Y, Chen F, Chang R, Trivedi M, Green KJ and Cryns VL: Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis. Cell Death Differ. 8:443–450. 2001. View Article : Google Scholar : PubMed/NCBI
86	Eckes B, Dogic D, Colucci-Guyon E, Wang N, Maniotis A, Ingber D, Merckling A, Langa F, Aumailley M, Delouvée A, et al: Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts. J Cell Sci. 111:1897–1907. 1998.PubMed/NCBI
87	Nieminen M, Henttinen T, Merinen M, Marttila-Ichihara F, Eriksson JE and Jalkanen S: Vimentin function in lymphocyte adhesion and transcellular migration. Nat Cell Biol. 8:156–162. 2006. View Article : Google Scholar : PubMed/NCBI
88	Sonoda K, Miyamoto S, Yamazaki A, Kobayashi H, Nakashima M, Mekada E and Wake N: Biologic significance of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) as a pivotal regulator of tumor growth through angiogenesis in human uterine cancer. Cancer. 110:1979–1990. 2007. View Article : Google Scholar : PubMed/NCBI
89	Liby TA, Spyropoulos P, Buff Lindner H, Eldridge J, Beeson C, Hsu T and Muise-Helmericks RC: Akt3 controls vascular endothelial growth factor secretion and angiogenesis in ovarian cancer cells. Int J Cancer. 130:532–543. 2012. View Article : Google Scholar : PubMed/NCBI
90	Davis GE and Senger DR: Endothelial extracellular matrix: Biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ Res. 97:1093–1107. 2005. View Article : Google Scholar : PubMed/NCBI
91	American Cancer Society: Global Cancer Facts & Figures (3rd). Atlanta, GA: American Cancer Society. 34–36. 2015.
92	Schiffman M, Castle PE, Jeronimo J, et al: Human papillomavirus and cervical cancer. Lancet. 370:890–907. 2007. View Article : Google Scholar : PubMed/NCBI
93	Burk RD, Chen Z and Van Doorslaer K: Human papillomaviruses: Genetic basis of carcinogenicity. Public Health Genomics. 12:281–290. 2009. View Article : Google Scholar : PubMed/NCBI
94	Moody CA and Laimins LA: Human papillomavirus oncoproteins: Pathways to transformation. Nat Rev Cancer. 10:550–560. 2010. View Article : Google Scholar : PubMed/NCBI
95	Buck CB, Day PM and Trus BL: The papillomavirus major capsid protein L1. Virology. 445:169–174. 2013. View Article : Google Scholar : PubMed/NCBI
96	Mammas IN, Sourvinos G, Giannoudis A and Spandidos DA: Human papilloma virus (HPV) and host cellular interactions. Pathol Oncol Res. 14:345–354. 2008. View Article : Google Scholar : PubMed/NCBI
97	Huang KF, Lee WY, Huang SC, Lin YS, Kang CY, Liou CP and Tzeng CC: Chromosomal gain of 3q and loss of 11q often associated with nodal metastasis in early stage cervical squamous cell carcinoma. J Formos Med Assoc. 106:894–902. 2007. View Article : Google Scholar : PubMed/NCBI
98	Giarnieri E, Zanesi N, Bottoni A, Alderisio M, Lukic A, Vecchione A, Ziparo V, Croce CM and Mancini R: Oncosuppressor proteins of fragile sites are reduced in cervical cancer. Cancer Lett. 289:40–45. 2010. View Article : Google Scholar : PubMed/NCBI
99	Samir R, Asplund A, Tot T, Pekar G and Hellberg D: High-risk HPV infection and CIN grade correlates to the expression of c-myc, CD4+, FHIT, E-cadherin, Ki-67, and p16INK4a. J Low Genit Tract Dis. 15:280–286. 2011. View Article : Google Scholar : PubMed/NCBI
100	Spandidos DA, Dokianakis DN, Kallergi G and Aggelakis E: Molecular basis of gynecological cancer. Ann N Y Acad Sci. 900:56–64. 2000. View Article : Google Scholar : PubMed/NCBI
101	Sonoda K, Kaku T, Kamura T, Nakashima M, Watanabe T and Nakano H: Tumor-associated antigen 22-1-1 expression in the uterine cervical squamous neoplasia. Clin Cancer Res. 4:1517–1520. 1998.PubMed/NCBI
102	Wright JD, Barrena Medel NI, Sehouli J, Fujiwara K and Herzog TJ: Contemporary management of endometrial cancer. Lancet. 379:1352–1360. 2012. View Article : Google Scholar : PubMed/NCBI
103	American Cancer Society: Cancer facts & figures 2015. Atlanta, GA: American Cancer Society. 24–25. 2015.
104	Sorosky JI: Endometrial cancer. Obstet Gynecol. 120:383–397. 2012. View Article : Google Scholar : PubMed/NCBI
105	Koornstra JJ, Mourits MJ, Sijmons RH, Leliveld AM, Hollema H and Kleibeuker JH: Management of extracolonic tumours in patients with Lynch syndrome. Lancet Oncol. 10:400–408. 2009. View Article : Google Scholar : PubMed/NCBI
106	Matias-Guiu X and Prat J: Molecular pathology of endometrial carcinoma. Histopathology. 62:111–123. 2013. View Article : Google Scholar : PubMed/NCBI
107	Banno K, Yanokura M, Iida M, Masuda K and Aoki D: Carcinogenic mechanisms of endometrial cancer: Involvement of genetics and epigenetics. J Obstet Gynaecol Res. 40:1957–1967. 2014. View Article : Google Scholar : PubMed/NCBI
108	Niwa K, Murase T, Furui T, Morishita S, Mori H, Tanaka T, Mori H and Tamaya T: Enhancing effects of estrogens on endometrial carcinogenesis initiated by N-methyl-N-nitrosourea in ICR mice. Jpn J Cancer Res. 84:951–955. 1993. View Article : Google Scholar : PubMed/NCBI
109	Ohgami T and Kato K: Pathogenesis of endometrial cancer. Current Approaches to Endometrial Cancer. Sakuragi N and Silverberg SG: (London). Future Medicine. 18–32. 2014.
110	Yeramian A, Moreno-Bueno G, Dolcet X, Catasus L, Abal M, Colas E, Reventos J, Palacios J, Prat J and Matias-Guiu X: Endometrial carcinoma: Molecular alterations involved in tumor development and progression. Oncogene. 32:403–413. 2013. View Article : Google Scholar : PubMed/NCBI
111	MacDonald ND, Salvesen HB, Ryan A, Iversen OE, Akslen LA and Jacobs IJ: Frequency and prognostic impact of microsatellite instability in a large population-based study of endometrial carcinomas. Cancer Res. 60:1750–1752. 2000.PubMed/NCBI
112	Hecht JL and Mutter GL: Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol. 24:4783–4791. 2006. View Article : Google Scholar : PubMed/NCBI
113	Halperin R, Zehavi S, Habler L, Hadas E, Bukovsky I and Schneider D: Comparative immunohistochemical study of endometrioid and serous papillary carcinoma of endometrium. Eur J Gynaecol Oncol. 22:122–126. 2001.PubMed/NCBI
114	Holcomb K, Delatorre R, Pedemonte B, McLeod C, Anderson L and Chambers J: E-cadherin expression in endometrioid, papillary serous, and clear cell carcinoma of the endometrium. Obstet Gynecol. 100:1290–1295. 2002. View Article : Google Scholar : PubMed/NCBI
115	Sonoda K, Kaku T, Hirakawa T, Kobayashi H, Amada S, Sakai K, Nakashima M, Watanabe T and Nakano H: The clinical significance of tumor-associated antigen RCAS1 expression in the normal, hyperplastic, and malignant uterine endometrium. Gynecol Oncol. 79:424–429. 2000. View Article : Google Scholar : PubMed/NCBI
116	Sonoda K, Miyamoto S, Hirakawa T, Kaku T, Nakashima M, Watanabe T, Akazawa K, Fujita T and Nakano H: Association between RCAS1 expression and clinical outcome in uterine endometrial cancer. Br J Cancer. 89:546–551. 2003. View Article : Google Scholar : PubMed/NCBI
117	Landen CN Jr, Birrer MJ and Sood AK: Early events in the pathogenesis of epithelial ovarian cancer. J Clin Oncol. 26:995–1005. 2008. View Article : Google Scholar : PubMed/NCBI
118	Gui T, Cao D, Yang J and Shen K: Tumor heterogeneity has important consequences for personalized medicine in ovarian cancer. Histol Histopathol. 30:173–181. 2015.PubMed/NCBI
119	Mayr D, Hirschmann A, Löhrs U and Diebold J: KRAS and BRAF mutations in ovarian tumors: A comprehensive study of invasive carcinomas, borderline tumors and extraovarian implants. Gynecol Oncol. 103:883–887. 2006. View Article : Google Scholar : PubMed/NCBI
120	O'Neill CJ, Deavers MT, Malpica A, Foster H and McCluggage WG: An immunohistochemical comparison between low-grade and high-grade ovarian serous carcinomas: Significantly higher expression of p53, MIB1, BCL2, HER-2/neu, and C-KIT in high-grade neoplasms. Am J Surg Pathol. 29:1034–1041. 2005.PubMed/NCBI
121	Nowee ME, Snijders AM, Rockx DA, de Wit RM, Kosma VM, Hämäläinen K, Schouten JP, Verheijen RH, van Diest PJ, Albertson DG and Dorsman JC: DNA profiling of primary serous ovarian and fallopian tube carcinomas with array comparative genomic hybridization and multiplex ligation-dependent probe amplification. J Pathol. 213:46–55. 2007. View Article : Google Scholar : PubMed/NCBI
122	Wiegand KC, Hennessy BT, Leung S, Wang Y, Ju Z, McGahren M, Kalloger SE, Finlayson S, Stemke-Hale K, Lu Y, et al: A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: Protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation. BMC Cancer. 14:1202014. View Article : Google Scholar : PubMed/NCBI
123	Naik JD, Seligmann J and Perren TJ: Mucinous tumours of the ovary. J Clin Pathol. 65:580–584. 2012. View Article : Google Scholar : PubMed/NCBI
124	George SH and Shaw P: BRCA and early events in the development of serous ovarian cancer. Front Oncol. 4:52014. View Article : Google Scholar : PubMed/NCBI
125	Powell SN and Kachnic LA: Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation. Oncogene. 22:5784–5791. 2003. View Article : Google Scholar : PubMed/NCBI
126	Venkitaraman AR: Linking the cellular functions of BRCA genes to cancer pathogenesis and treatment. Annu Rev Pathol. 4:461–487. 2009. View Article : Google Scholar : PubMed/NCBI
127	Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, Jack E, Vesprini DJ, Kuperstein G, Abrahamson JL, et al: Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet. 68:700–710. 2001. View Article : Google Scholar : PubMed/NCBI
128	Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, et al: Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: A combined analysis of 22 studies. Am J Hum Genet. 72:1117–1130. 2003. View Article : Google Scholar : PubMed/NCBI
129	McLaughlin JR, Risch HA, Lubinski J, et al: Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: A case-control study. Lancet Oncol. 8:26–34. 2007. View Article : Google Scholar : PubMed/NCBI
130	Liu JF, Konstantinopoulos PA and Matulonis UA: PARP inhibitors in ovarian cancer: Current status and future promise. Gynecol Oncol. 133:362–369. 2014. View Article : Google Scholar : PubMed/NCBI
131	Ledermann J, Harter P, Gourley C, et al: Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 366:1382–1392. 2012. View Article : Google Scholar : PubMed/NCBI
132	Fujita T, Miyamoto S, Onoyama I, et al: Expression of lysophosphatidic acid receptors and vascular endothelial growth factor mediating lysophosphatidic acid in the development of human ovarian cancer. Cancer Lett. 192:161–169. 2003. View Article : Google Scholar : PubMed/NCBI
133	Yotsumoto F, Yagi H, Suzuki SO, et al: Validation of HB-EGF and amphiregulin as targets for human cancer therapy. Biochem Biophys Res Commun. 365:555–561. 2008. View Article : Google Scholar : PubMed/NCBI
134	Yagi H, Yotsumoto F, Sonoda K, et al: Synergistic anti-tumor effect of paclitaxel with CRM197, an inhibitor of HB-EGF, in ovarian cancer. Int J Cancer. 124:1429–1439. 2009. View Article : Google Scholar : PubMed/NCBI