Endometrial Carcinogenesis and Molecular Signaling Pathways


The Endometrial Cancer (EC) is the most common gynecologic malignancy that starts in the endometrium of women. Carcinogenesis of EC is associated with several critical regulatory molecules, which involve in different signaling pathways. A number of signaling pathways have been identified to be involved in the multiple-step development of EC, including PI3K/AKT/mTOR signaling pathway, WNT/β-catenin signal transduction cascades (including APC/β-catenin pathway), MAPK/ERK pathway, VEGF/VEGFR ligand receptor signaling pathway, ErbB signaling pathway, P53/P21 and P16INK4a/pRB signaling pathways. This review mainly focuses on the molecular signaling pathways relevant to human endometrial cancer and discusses those critical capabilities of transforming endometrial cells, including evading apoptosis; enhancing cell proliferation; blocking differentiation; and inducing angiogenesis.

Share and Cite:

Ma, X. , Ma, C. and Wang, J. (2014) Endometrial Carcinogenesis and Molecular Signaling Pathways. American Journal of Molecular Biology, 4, 134-149. doi: 10.4236/ajmb.2014.43015.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Laplante, M. and Sabatini, D.M. (2009) mTOR Signaling at a Glance. Journal of Cell Science, 122, 3589-3594.
[2] Hagiwara, A., Cornu, M., Cybulski, N., Polak, P., Betz, C., Trapani, F., Terracciano, L., Heim, M.H., Rüegg, M.A. and Hallemail, M.N. (2012) Hepatic mTORC2 Activates Glycolysis and Lipogenesis through Akt, Glucokinase, and SREBP1c. Cell Metabolism, 15, 725-738.
[3] Risinger, J.I., Hayes, K., Maxwell, G.L., Carney, M.E., Dodge, R.K., Barrett, J.C. and Berchuck, A. (1998) PTEN Mutation in Endometrial Cancers Is Associated with Favorable Clinical and Pathologic Characteristics. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 4, 3005-3010.
[4] Cancer Genome Atlas Research Networks (2013) Integrated Genomic Characterization of Endometrial Carcinoma. Nature, 497, 67-73.
[5] Cheung, L.W.T., Hennessy, B.T., Jie, L., Yu, S.X., Myers, A.P., Djordjevic, B., Lu, Y.L., Stemke-Hale, K., Dyer, M.D., Zhang, F., Ju, Z.L., Cantley, L.C., Scherer, S.E., Liang, H., Lu, K.H., Broaddus, R.R. and Mills, G.B. (2011) High Frequency of PIK3R1 and PIK3R2 Mutations in Endometrial Cancer Elucidates a Novel Mechanism for Regulation of PTEN Protein Stability. Cancer Discovery, 1, 170-185. http://dx.doi.org/10.1158/2159-8290.CD-11-0039
[6] Oda, K. (2011) Targeting Ras-PI3K/mTOR Pathway and the Predictive Biomarkers in Endometrial Cancer. Gan to Kagakuryoho. Cancer & Chemotherapy, 38, 1084-1087.
[7] Salvesen, H.B., Carter, S.L., Mannelqvist, M., Duttd, A., Getz, G., Stefansson, I.M., Raeder, M.B., Sos, M.L., Engelsen, I.B., Trovik, J., Wik, E., Greulich, H., Bø, T.H., Jonassen, I., Thomas, R.K., Zanderh, T., Garraway, L.A., Øyan, A.M., Sellers, W.R., Kalland, K.H., Meyerson, M., Akslen, L.A. and Beroukhim, R. (2009) Integrated Genomic Profiling of Endometrial Carcinoma Associates Aggressive Tumors with Indicators of PI3 Kinase Activation. Proceedings of the National Academy of Sciences of the United States of America, 106, 4834-4839.
[8] Dedes, K.J., Wetterskog, D., Ashworth, A., Kaye, S.B. and Jorge, S. (2011) Emerging Therapeutic Targets in Endometrial Cancer. Nature Reviews. Clinical Oncology, 8, 261-271.
[9] Uegaki, K., Kanamori, Y., Kigawa, J., Kawaguchi, W., Kaneko, R., Naniwa, J., Takahashi, M., Shimada, M., Oishi, T., Itamochi, H. and Terakawa, N. (2005) PTEN-Positive and Phosphorylated-Akt-Negative Expression Is a Predictor of Survival for Patients with Advanced Endometrial Carcinoma. Oncology Reports, 14, 389-392.
[10] Franke, T.F., Hornik C.P., Segev, L., Shostak, G.A. and Sugimoto, C. (2003) PI3K/Akt and Apoptosis: Size Matters. Oncogene, 22, 8983-8998.
[11] Hennessy, B.T., Smith, D.L., Ram, P.T., Lu, Y.L. and Mill, G.B. (2005) Exploiting the PI3K/AKT Pathway for Cancer Drug Discovery. Nature Reviews. Drug Discovery, 4, 988-1004.
[12] Yap, T.A., Garrett, M.D., Walton, M.I., Raynaud, F., de Bono, J.S. and Workman, P. (2008) Targeting the PI3K-AKT-mTOR Pathway: Progress, Pitfalls, and Promises. Current Opinion in Pharmacology, 8, 393-412.
[13] Lacey Jr., J.V., Yang, H., Gaudet, M.M., Dunning, A., Lissowska, J., Sherman, M.E., Peplonska, B., Brinton, L.A., Healey, C.S., Ahmed, S., Pharoah, P., Easton, D., Chanock, S. and Garcia-Closas, M. (2011) Endometrial Cancer and Genetic Variation in PTEN, PIK3CA, AKT1, MLH1, and MSH2 within a Population-Based Case-Control Study. Gynecologic Oncology, 120, 167-173.
[14] Krakstad, C., Birkeland, E., Seidel, D., Kusonmano, K., Petersen, K., Mjøs, S., Hoivik, E.A., Wik, E., Halle, M.K., Øyan, A.M., Kalland, K.-H., Werner, H.M.J., Trovik, J. and Salvesen, H. (2012) High-Throughput Mutation Profiling of Primary and Metastatic Endometrial Cancers Identifies KRAS, FGFR2 and PIK3CA to Be Frequently Mutated. PloS One, 7, Article ID: e52795.
[15] Abe, N., Watanabe, J., Tsunoda, S., Kuramoto, H. and Okayasu, I. (2011) Significance of Nuclear p-Akt in Endometrial Carcinogenesis: Rapid Translocation of p-Akt into the Nucleus by Estrogen, Possibly Resulting in Inhibition of Apoptosis. International Journal of Gynecological Cancer: Official Journal of the International Gynecological Cancer Society, 21, 194-202.
[16] Mori, N., Kyo, S., Sakaguchi, J., Mizumoto, Y., Ohno, S., Maida, Y., Hashimoto, M., Takakura, M. and Inoue, M. (2007) Concomitant Activation of AKT with Extracellular-Regulated Kinase 1/2 Occurs Independently of PTEN or PIK3CA Mutations in Endometrial Cancer and May Be Associated with Favorable Prognosiss. Cancer Science, 98, 1881-1888.
[17] Hoshino, R., Chatani, Y., Yamori, T., Tsuruo, T., Oka, H., Yoshida, O., Shimada, Y., Ari-i, S., Wada, H., Fujimoto, J. and Kohno, M. (1999) Constitutive Activation of the 41-/43-kDa Mitogen-Activated Protein Kinase Signaling Pathway in Human Tumors. Oncogene, 18, 813-822.
[18] Alexander-Sefre, F., Salvesen, H.B., Ryan, A., Singh, N., Akslen, L.A., MacDonald, N., Wilbanks, G. and Jacobs, I.J. (2003) Molecular Assessment of Depth of Myometrial Invasion in Stage I Endometrial Cancer: A Model Based on K-ras Mutation Analysis. Gynecologic Oncology, 91, 218-225.
[19] Mizuuchi, H., Nasim, S., Kudo, R., Silverberg, S.G., Greenhouse, S. and Garrett, C.T. (1992) Clinical Implications of K-ras Mutations in Malignant Epithelial Tumors of the Endometrium. Cancer Research, 52, 2777-2781.
[20] Matias-Guiu, X., Catasus, L., Bussaglia, E., Lagarda, H., Garcia, A., Pons, C., Muñoz, J., Argüelles, R., Machin, P. and Prat, J. (2001) Molecular Pathology of Endometrial Hyperplasia and Carcinoma. Human Pathology, 32, 569-577.
[21] Prat, J., Gallardo, A., Cuatrecasas, M. and Catasús, L. (2007) Endometrial Carcinoma: Pathology and Genetics. Pathology, 39, 72-87.
[22] Dobrzycka, B., Terlikowski, S.J., et al. (2009) Mutations of the KRAS Oncogene in Endometrial Hyperplasia and Carcinoma. Folia Histochemica et Cytobiologica/Polish Academy of Sciences, Polish Histochemical and Cytochemical Society, 47, 65-68.
[23] Ito, K., Watanabe, K., Nasim, S., Sasano, H., Sato, S., Yajima, A., Silverberg, S.G. and Garrett, C.T. (1996) K-RAS Point Mutations in Endometrial Carcinoma: Effect on Outcome Is Dependent on Age of Patient. Gynecologic Oncology, 63, 238-246.
[24] Kestler, H.A. and Kuhl, M. (2008) From Individual Wnt Pathways towards a Wnt Signalling Network. Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 363, 1333-1347.
[25] Logan, C.Y. and Nusse, R. (2004) The Wnt Signaling Pathway in Development and Disease. Annual Review of Cell and Developmental Biology, 20, 781-810.
[26] Kuhl, M., Sheldahl, L.C., Malbon, C.C. and Moon, R.T. (2000) Ca2+/Calmodulin-Dependent Protein Kinase II Is Stimulated by Wnt and Frizzled Homologs and Promotes Ventral Cell Fates in Xenopus. Journal of Biological Chemistry, 275, 12701-12711.
[27] Veeman, M.T., Axelrod, J.D. and Moon, R.T. (2003) A Second Canon. Functions and Mechanisms of β-Catenin-Independent Wnt Signaling. Developmental Cell, 5, 367-377.
[28] Wang, Y., Hanifi-Moghaddam, P., Hanekamp, E.E., Kloosterboer, H.J., Franken, P., Veldscholte, J., van Doorn, H.C., Ewing, P.C., Kim, J.J., Grootegoed, J.A., Burger, C.W., Fodde, R. and Blok, L.J. (2009) Progesterone Inhibition of Wnt/β-Catenin Signaling in Normal Endometrium and Endometrial Cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 15, 5784-5793.
[29] Martens, B., Amman, F., Manoharadas, S., Zeichen, L., Orell, A., Albers, S.V., Hofacker, I. and Blãsi, U. (2013) Alterations of the Transcriptome of Sulfolobus acidocaldarius by Exoribonuclease aCPSF2. PLoS ONE, 8, Article ID: e76569.
[30] Wang, Y., van der Zee, M., Fodde, R. and Blok, L.J. (2010) Wnt/β-Catenin and Sex Hormone Signaling in Endometrial Homeostasis and Cancer. Oncotarget, 1, 674-684.
[31] Sharpe, C., Lawrence, N. and Arias, A.M. (2001) Wnt Signalling: A Theme with Nuclear Variations. BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology, 23, 311-318.
[32] Aberle, H., Bauer, A., Stappert, J., Kispert, A. and Kemler, R. (1997) β-Catenin Is a Target for the Ubiquitin-Proteasome Pathway. The EMBO Journal, 16, 3797-3804.
[33] Palacios, J., Catasus, L., Moreno-Bueno, G., Matias-Guiu, X., Prat, J. and Gamallo, C. (2001) Beta- and Gamma- Catenin Expression in Endometrial Carcinoma. Relationship with Clinicopathological Features and Microsatellite Instability. Virchows Archiv: An International Journal of Pathology, 438, 464-469.
[34] Moreno-Bueno, G., Hardisson, D., Sánchez, C., Sarrió, D., Cassia, R., García-Rostán, G., Prat, J., Guo, M., Herman, J.G., Matías-Guiu, X., Esteller, M. and Palacios, J. (2002) Abnormalities of the APC/β-Catenin Pathway in Endometrial Cancer. Oncogene, 21, 7981-7990.
[35] Kolligs, F.T., Kolligs, B., Hajra, K.M., Hu, G., Tani, M., Cho, K.R. and Fearon, E.R. (2000) Gamma-Catenin Is Regulated by the APC Tumor Suppressor and Its Oncogenic Activity Is Distinct from that of β-Catenin. Genes & Development, 14, 1319-1331.
[36] Senger, D.R., Galli, S.J., Dvorak, A.M., Perruzzi, C.A., Harvey, V.S. and Dvorak, H.F. (1983) Tumor Cells Secrete a Vascular Permeability Factor that Promotes Accumulation of Ascites Fluid. Science, 219, 983-985.
[37] Ferrara, N. (2002) VEGF and the Quest for Tumour Angiogenesis Factors. Nature Reviews Cancer, 2, 795-803.
[38] Hicklin, D.J. and Ellis, L.M. (2005) Role of the Vascular Endothelial Growth Factor Pathway in Tumor Growth and Angiogenesis. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 23, 1011-1027.
[39] Kawasaki, T., Kitsukawa, T., Bekku, Y., Matsuda, Y., Sanbo, M., Yagi, T. and Fujisawa, H. (1999) A Requirement for Neuropilin-1 in Embryonic Vessel Formation. Development, 126, 4895-4902.
[40] Ferrer, F.A., Miller, L.J., Lindquist, R., Kowalczyk, P., Laudone, V.P., Albertsen, P.C. and Kreutzer, D.L. (1999) Expression of Vascular Endothelial Growth Factor Receptors in Human Prostate Cancer. Urology, 54, 567-572.
[41] Decaussin, M., Sartelet, H., Robert, C., Moro, D., Claraz, C., Brambilla, C. and Brambilla, E. (1999) Expression of Vascular Endothelial Growth Factor (VEGF) and Its Two Receptors (VEGF-R1-Flt1 and VEGF-R2-Flk1/KDR) in Non-Small Cell Lung Carcinomas (NSCLCs): Correlation with Angiogenesis and Survival. The Journal of Pathology, 188, 369-377.
[42] Dumont, D.J., Jussila, L., Taipale, J., Lymboussaki, A., Mustonen, T., Pajusola, K., Breitman, M. and Alitalo, K. (1998) Cardiovascular Failure in Mouse Embryos Deficient in VEGF Receptor-3. Science, 282, 946-949.
[43] Achen, M.G., Williams, R.A., Minekus, M.P., Thornton, G.E., Stenvers, K., Rogers, P.A.W., Lederman, F., Roufail, S. and Stacker, S.A. (2001) Localization of Vascular Endothelial Growth Factor-D in Malignant Melanoma Suggests a Role in Tumour Angiogenesis. The Journal of Pathology, 193, 147-154.
[44] Ohta, Y., Shridhar, V., Bright, R.K., Kalemkerian, G.P., Du, W., Carbone, M., Watanabe, Y. and Pass, H.I. (1999) VEGF and VEGF Type C Play an Important Role in Angiogenesis and Lymphangiogenesis in Human Malignant Mesothelioma Tumours. British Journal of Cancer, 81, 54-61.
[45] Folkman, J. (1990) What Is the Evidence that Tumors Are Angiogenesis Dependent? Journal of the National Cancer Institute, 82, 4-6.
[46] Fong, G.H., Rossant, J., Gertsenstein, M. and Breitman, M.L. (1995) Role of the Flt-1 Receptor Tyrosine Kinase in Regulating the Assembly of Vascular Endothelium. Nature, 376, 66-70.
[47] Thurston, G., Suri, C., Smith, K., McClain, J., Sato, T.N., Yancopoulos, G.D. and McDonald, D.M. (1999) Leakage-Resistant Blood Vessels in Mice Transgenically Overexpressing Angiopoietin-1. Science, 286, 2511-2514.
[48] Holland, C.M., Day, K., Evans, A. and Smith, S.K. (2003) Expression of the VEGF and Angiopoietin Genes in Endometrial Atypical Hyperplasia and Endometrial Cancer. British Journal of Cancer, 89, 891-898.
[49] Yokoyama, Y., Charnock-Jones, D.S., Licence, D., Yanaihara, A., Hastings, J.M., Holland, C.M., Emoto, M., Sakamoto, A., Sakamoto, T., Maruyama, H., Sato, S., Mizunuma, H. and Smith, S.K. (2003) Expression of Vascular Endothelial Growth Factor (VEGF)-D and Its Receptor, VEGF Receptor 3, as a Prognostic Factor in Endometrial Carcinoma. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 9, 1361-1369.
[50] Burgess, A.W., Cho, H.S., Eigenbrot, C., Ferguson, K.M., Garrett, T.P.J., Leahy, D.J., et al. (2003) An Open-and-Shut Case? Recent Insights into the Activation of EGF/ErbB Receptors. Molecular Cell, 12, 541-552.
[51] Zhang, H.T., Berezov, A., Wang, Q., Zhang, G., Drebin, J., Murali, R. and Greene, M.I. (2007) ErbB Receptors: From Oncogenes to Targeted Cancer Therapies. The Journal of Clinical Investigation, 117, 2051-2058.
[52] Zhou, S.Y., Margolis, B., Chaudhuri, M., Shoelson, S.E. and Cantley, L.C. (1995) The Phosphotyrosine Interaction Domain of SHC Recognizes Tyrosine-Phosphorylated NPXY Motif. The Journal of Biological Chemistry, 270, 14863-14866.
[53] Yarden, Y. and Sliwkowski, M.X. (2001) Untangling the ErbB Signalling Network. Nature Reviews Molecular Cell Biology, 2, 127-137.
[54] Cuevas, B.D., Lu, Y.L., Mao, M.L., Zhang, J.Y., LaPushin, R., Siminovitch, K. and Mills, G.B. (2001) Tyrosine Phosphorylation of p85 Relieves Its Inhibitory Activity on Phosphatidylinositol 3-Kinase. The Journal of Biological Chemistry, 276, 27455-27461.
[55] Jiang, X.N., Chen, S., Asara, J.M. and Balk, S.P. (2010) Phosphoinositide 3-Kinase Pathway Activation in Phosphate and Tensin Homolog (PTEN)-Deficient Prostate Cancer Cells Is Independent of Receptor Tyrosine Kinases and Mediated by the p110β and p110δ Catalytic Subunits. The Journal of Biological Chemistry, 285, 14980-14989.
[56] Haura, E.B., Turkson, J. and Jove, R. (2005) Mechanisms of Disease: Insights into the Emerging Role of Signal Transducers and Activators of Transcription in Cancer. Nature Clinical Practice Oncology, 2, 315-324.
[57] Pallares, J., Martinez-Guitarte, J.L., et al. (2005) Survivin Expression in Endometrial Carcinoma: A Tissue Microarray Study with Correlation with PTEN and STAT-3. International Journal of Gynecological Pathology: Official Journal of the International Society of Gynecological Pathologists, 24, 247-253.
[58] Catalano, S., Giordano, C., et al. (2009) Evidence That Leptin through STAT and CREB Signaling Enhances Cyclin D1 Expression and Promotes Human Endometrial Cancer Proliferation. Journal of Cellular Physiology, 218, 490-500.
[59] Irby, R.B., McCarthy, S.M. and Yeatman, T.J. (2004) Osteopontin Regulates Multiple Functions Contributing to Human Colon cancer Development and Progression. Clinical & Experimental Metastasis, 21, 515-523.
[60] Summy, J.M. and Gallick, G.E. (2006) Treatment for Advanced Tumors: SRC Reclaims Center Stage. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 12, 1398-1401.
[61] Sakaguchi, H., Fujimoto, J., et al. (2007) Clinical Implications of Steroid Receptor Coactivator (SRC)-3 in Uterine Endometrial Cancers. The Journal of Steroid Biochemistry and Molecular Biology, 104, 237-240.
[62] Balmer, N.N., Richer, J.K., et al. (2006) Steroid Receptor Coactivator AIB1 in Endometrial Carcinoma, Hyperplasia and Normal Endometrium: Correlation with Clinicopathologic Parameters and Biomarkers. Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, 19, 1593-1605.
[63] Schonwasser, D.C., Marais, R.M., Marshall, C.J. and Parker, P.J. (1998) Activation of the Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway by Conventional, Novel, and Atypical Protein Kinase C Isotypes. Molecular and Cellular Biology, 18, 790-798.
[64] McClellan, M., Kievit, P., Auersperg, N. and Rodland, K. (1999) Regulation of Proliferation and Apoptosis by Epidermal Growth Factor and Protein Kinase C in Human Ovarian Surface Epithelial Cells. Experimental Cell Research, 246, 471-479.
[65] Miturski, R., Semczuk, A. and Jakowicki, J.A. (1998) C-erbB-2 Expression in Human Proliferative and Hyperplastic Endometrium. International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics, 61, 73-74.
[66] Ejskjaer, K., Sorensen, B.S., Poulsen, S.S., Forman, A., Nexø, E. and Mogensen, O. (2007) Expression of the Epidermal Growth Factor System in Endometrioid Endometrial Cancer. Gynecologic Oncology, 104, 158-167.
[67] Huang, T.H. and Morrison, S.L. (2006) A Trimeric Anti-HER2/neu ScFv and Tumor Necrosis Factor-α Fusion Protein Induces HER2/neu Signaling and Facilitates Repair of Injured Epithelia. The Journal of Pharmacology and Experimental Therapeutics, 316, 983-991.
[68] Konecny, G.E., Santos, L., Winterhoff, B., Hatmal, M., Keeney, G.L., Mariani, A., et al. (2009) HER2 Gene Amplification and EGFR Expression in a Large Cohort of Surgically Staged Patients with Nonendometrioid (Type II) Endometrial Cancer. British Journal of Cancer, 100, 89-95.
[69] Santin, A.D., Bellone, S., Siegel, E.R., Palmieri, M., Thomas, M., Cannon, M.J., Kay, H.H., Roman, J.J., Burnett, A. and Pecorelli, S. (2005) Racial Differences in the Overexpression of Epidermal Growth Factor Type II Receptor (HER2/neu): A Major Prognostic Indicator in Uterine Serous Papillary Cancer. American Journal of Obstetrics and Gynecology, 192, 813-818.
[70] Konecny, G.E., Santos, L., Winterhoff, B., Hatmal, M., Keeney, G.L., Mariani, A., et al. (2009) HER2 Gene Amplification and EGFR Expression in a Large Cohort of Surgically Staged Patients with Nonendometrioid (Type II) Endometrial Cancer. British Journal of Cancer, 100, 89-95.
[71] Lemoine, N.R., Barnes, D.M., Hollywood, D.P., Hughes, C.M., Smith, P., Dublin, E., Prigent, S.A., Gullick, W.J. and Hurst, H.C. (1992) Expression of the ERBB3 Gene Product in Breast Cancer. British Journal of Cancer, 66, 1116-1121.
[72] Srinivasan, R., Benton, E., McCormick, F., Thomas, H. and Gullick, W.J. (1999) Expression of the c-erbB-3/HER-3 and c-erbB-4/HER-4 Growth Factor Receptors and Their Ligands, Neuregulin-1 Alpha, Neuregulin-1 Beta, and Betacellulin, in Normal Endometrium and Endometrial Cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 5, 2877-2883.
[73] Ejskjaer, K., Sorensen, B.S., Poulsen, S.S., Forman, A., Nexø, E. and Mogensen, O. (2007) Expression of the Epidermal Growth Factor System in Endometrioid Endometrial Cancer. Gynecologic Oncology, 104, 158-167.
[74] Androutsopoulos, G., Adonakis, G., Liava, A., Ravazoula, P. and Decavalas, G. (2013) Expression and Potential Role of ErbB Receptors in Type II Endometrial Cancer. European Journal of Obstetrics, Gynecology and Reproductive Biology, 168, 204-208.
[75] Contessa, J.N., Abell, A., Mikkelsen, R.B., Valerie, K. and Schmidt-Ullrich, R.K. (2006) Compensatory ErbB3/c-SRC Signaling Enhances Carcinoma Cell Survival to Ionizing Radiation. Breast Cancer Research and Treatment, 95, 17-27. http://dx.doi.org/10.1007/s10549-005-9023-9
[76] Chobotova, K., Karpovich, N., Carver, J., Manek, S., Gullick, W.J., Barlow, D.H. and Mardon, H.J. (2005) Heparin-Binding Epidermal Growth Factor and Its Receptors Mediate Decidualization and Potentiate Survival of Human Endometrial Stromal Cells. The Journal of Clinical Endocrinology and Metabolism, 90, 913-919.
[77] Saghir, F.S.A., Rose, I.M., et al. (2010) Gene Expression Profiling and Cancer-Related Pathways in Type I Endometrial Carcinoma. International Journal of Gynecological Cancer, 20, 724-731.
[78] Janiec-Jankowska, A., Konopka, B., Goluda, C. and Najmola, U. (2010) Tp53 Mutations in Endometrial Cancers: Relation to PTEN Gene Defects. International Journal of Gynecological Cancer, 20, 196-202.
[79] Tashiro, H., Isacson, C., Levine, R., Kurman, R.J., Cho, K.R. and Hedrick, L. (1997) P53 Gene Mutations Are Common in Uterine Serous Carcinoma and Occur Early in Their Pathogenesis. The American Journal of Pathology, 150, 177-185.
[80] Kohlberger, P., Gitsch, G., Loesch, A., Tempfer, C., Kaider, A., Reinthaller, A., Kainz, C. and Breitenecker, G. (1996) P53 Protein Overexpression in Early Stage Endometrial Cancer. Gynecologic Oncology, 62, 213-217.
[81] Ito, K., Watanabe, K., Nasim, S., Sasano, H., Sato, S., Yajima, A., Silverberg, S.G. and Garrett, C.T. (1994) Prognostic Significance of P53 Overexpression in Endometrial Cancer. Cancer Research, 54, 4667-4670.
[82] Nakashima, R., Fujita, M., Enomoto, T., Haba, T., Yoshino, K., Wada, H., Kurachi, H., Sasaki, M., Wakasa, K., Inoue, M., Buzard, G. and Murata, Y. (1999) Alteration of p16 and p15 Genes in Human Uterine Tumours. British Journal of Cancer, 80, 458-467.
[83] Semczuk, A., Boltze, C., Marzec, B., Szczygielska, A., Roessner, A. and Schneider-Stock, R. (2003) p16INK4A Alterations Are Accompanied by Aberrant Protein Immunostaining in Endometrial Carcinomas. Journal of Cancer Research and Clinical Oncology, 129, 589-596.
[84] Guida, M., Sanguedolce, F., Bufo, P., Di Spiezio Sardo, A., Bifulco, G., Nappi, C. and Pannone, G. (2009) Aberrant DNA Hypermethylation of hMLH-1 and CDKN2A/p16 Genes in Benign, Premalignant and Malignant Endometrial Lesions. European Journal of Gynaecological Oncology, 30, 267-270.
[85] O’Hara, A.J. and Bell, D.W. (2012) The Genomics and Genetics of Endometrial Cancer. Advances in Genomics and Genetics, 2012, 33-47.
[86] Wong, Y.F., Cheung, T.H., Kit Lo, K.W., Yim, S.F., Yin Chan, L.K., Buhard, O., Duval, A., Hung Chung, T.K. and Hamelin, R. (2006) Detection of Microsatellite Instability in Endometrial Cancer: Advantages of a Panel of Five Mononucleotide Repeats over the National Cancer Institute Panel of Markers. Carcinogenesis, 27, 951-955.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.