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Immunohistochemistry as Biomarker Platform in Endometrial Cancer

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Biomarkers in Cancer

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Abstract

Endometrial cancer is the most common malignancy of the female genital tract in Western countries, and its incidence is rapidly increasing in Asia. The standard treatment for women with endometrial cancer is staging operation followed by adjuvant radiation therapy according to the risk factors for recurrence. These include tumor histology, differentiation grade, lymphovascular space invasion, myometrial invasion, lymph node metastasis, and disease stage. However, these factors are not accurate independent predictors of recurrence or prognosis in endometrial cancer. Therefore, several biomarkers have been investigated as potential predictive or prognostic factors, and immunohistochemical markers for endometrial cancer have been investigated extensively in the past decades. In this chapter, we review recent advances in the identification of immunohistochemical markers as predictive or prognostic markers in endometrial cancer.

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Abbreviations

CEA:

Carcinoembryonic Antigen

COX-2:

Cyclooxygenase-2

EGF:

Epidermal Growth Factor

FIGO:

The International Federation of Obstetrics and Gynecology

GLUT:

Glucose Transporter

HER-2:

Human Epidermal Growth Factor

HIF-1 Alpha:

Hypoxia-Induced Factor-1 Alpha

HNPCC:

Hereditary Nonpolyposis Colorectal Cancer

IL:

Interleukin

L1CAM:

L1 Cell Adhesion Molecule

MLH:

MutL Homolog

MMP:

Matrix Metalloproteinases

MMR gene:

Mismatch Repair Gene

MSH:

MutS Homolog

MSI:

Microsatellite Instability

mTOR:

Mammalian Target of Rapamycin

Op 18:

Oncoprotein 18

P53:

Phosphoprotein p53

PD-ECGF:

Platelet-Derived Endothelial Cell Growth Factor

PG:

Prostaglandin

PIK3:

Phosphatidylinositol 3-Kinase

PTEN:

Phosphatase and Tensin Homolog

STMN 1:

Stathmin 1

TGF-alpha:

Transforming Growth Factor Alpha

VEGF:

Vascular Endothelial Growth Factor

References

  • Aglund K, Rauvala M, Puistola U, Angstrom T, Turpeenniemi-Hujanen T, Zackrisson B, Stendahl U. Gelatinases A and B (MMP-2 and MMP-9) in endometrial cancer-MMP-9 correlates to the grade and the stage. Gynecol Oncol. 2004;94:699–704.

    CAS  PubMed  Google Scholar 

  • Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I. Endometrial cancer. Lancet. 2005;366:491–505.

    PubMed  Google Scholar 

  • Banno K, Nogami Y, Kisu I, Yanokura M, Umene K, Masuda K, Kobayashi Y, Yamagami W, Susumu N, Aoki D. Candidate biomarkers for genetic and clinicopathological diagnosis of endometrial cancer. Int J Mol Sci. 2013;14:12123–37.

    PubMed Central  PubMed  Google Scholar 

  • Barbati A, Mariani L, Porpora MG, Anceschi M, Collini P, Lauro V, Cosmi EV. Serum evaluation of p53 protein in patients with gynaecological cancer. Anticancer Res. 2000;20(2A):1003–5.

    Google Scholar 

  • Ben-Hur H, Berman V, Sandler B, Smimoff P, Gurevich P, Open M, Zusman I. Serological and immunohistochemical determinations of p53 protein in diagnosis of endometrial cancer: a comparative study. Eur J Gynaecol Oncol. 1997;18(5):400–6.

    CAS  PubMed  Google Scholar 

  • Bilbao C, Lara PC, Ramirez R, Henriquez-Hernandez LA, Rodriguez G, Falcon O, Leon L, Perucho M, Diaz-Chico BN, Diaz-Chico JC. Microsatellite instability predicts clinical outcome in radiation-treated endometrioid endometrial cancer. Int J Radiat Oncol Biol Phys. 2010;76:9–13.

    PubMed Central  PubMed  Google Scholar 

  • Bray F, Loos AH, Oostindier M, Weiderpass E. Geographic and temporal variations in cancer of the corpus uteri: incidence and mortality in pre- and postmenopausal women in Europe. Int J Cancer. 2005;117:123–31.

    CAS  PubMed  Google Scholar 

  • Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002;296:1655–7.

    CAS  PubMed  Google Scholar 

  • Cao QJ, Einstein MH, Anderson PS, Runowicz CD, Balan R, Jones JG. Expression of COX-2, Ki-67, cyclin D1, and P21 in endometrial endometrioid carcinomas. Int J Gynecol Pathol. 2002;21:147–54.

    PubMed  Google Scholar 

  • Catasus L, Machin P, Matias-Guiu X, Prat J. Microsatellite instability in endometrial carcinomas: clinicopathologic correlations in a series of 42 cases. Hum Pathol. 1998;29:1160–4.

    CAS  PubMed  Google Scholar 

  • Catasus L, Gallardo A, Cuatrecasas M, Prat J. PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters. Mod Pathol. 2008;21:131–9.

    CAS  PubMed  Google Scholar 

  • Choi KC, Kang SK, Tai CJ, Auersperg N, Leung PC. Estradiol up-regulates antiapoptotic Bcl-2 messenger ribonucleic acid and protein in tumorigenic ovarian surface epithelium cells. Endocrinology. 2001;142:2351–60.

    CAS  PubMed  Google Scholar 

  • Clarke BA, Gilks CB. Endometrial carcinoma: controversies in histopathological assessment of grade and tumour cell type. J Clin Pathol. 2010;63:410–5.

    PubMed  Google Scholar 

  • Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C, Sessa C, ESMO Guidelines Working Group. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24 Suppl 6:vi33–8.

    PubMed  Google Scholar 

  • Curran S, Dundas SR, Buxton J, Leeman MF, Ramsay R, Murray GI. Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers. Clin Cancer Res. 2004;10:8229–34.

    CAS  PubMed  Google Scholar 

  • Dousias V, Vrekoussis T, Navrozoglou I, Paschopoulos M, Stefos T, Makrigiannakis A, Jeschke U. Hypoxia-induced factor-1alpha in endometrial carcinoma: a mini-review of current evidence. Histol Histopathol. 2012;27:1247–53.

    CAS  PubMed  Google Scholar 

  • Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002;2:161–74.

    CAS  PubMed  Google Scholar 

  • Ejskjaer K, Sorensen BS, Poulsen SS, Forman A, Nexo E, Mogensen O. Expression of the epidermal growth factor system in endometrioid endometrial cancer. Gynecol Oncol. 2007;104:158–67.

    CAS  PubMed  Google Scholar 

  • Espinosa I, Jose Carnicer M, Catasus L, Canet B, D'Angelo E, Zannoni GF, Prat J. Myometrial invasion and lymph node metastasis in endometrioid carcinomas: tumor-associated macrophages, microvessel density, and HIF1A have a crucial role. Am J Surg Pathol. 2010;34:1708–14.

    PubMed  Google Scholar 

  • Esteller M, Levine R, Baylin SB, Ellenson LH, Herman JG. MLH1 promoter hypermethylation is associated with the microsatellite instability phenotype in sporadic endometrial carcinomas. Oncogene. 1998;17:2413–7.

    CAS  PubMed  Google Scholar 

  • Feng YZ, Shiozawa T, Horiuchi A, Shih HC, Miyamoto T, Kashima H, Suzuki A, Nikaido T, Konishi I. Intratumoral heterogeneous expression of p53 correlates with p53 mutation, Ki-67, and cyclin A expression in endometrioid-type endometrial adenocarcinomas. Virchows Arch. 2005;447(5):816–22.

    CAS  PubMed  Google Scholar 

  • Ferrandina G, Legge F, Ranelletti FO, Zannoni GF, Maggiano N, Evangelisti A, Mancuso S, Scambia G, Lauriola L. Cyclooxygenase-2 expression in endometrial carcinoma: correlation with clinicopathologic parameters and clinical outcome. Cancer. 2002;95:801–7.

    CAS  PubMed  Google Scholar 

  • Fosslien E. Molecular pathology of cyclooxygenase-2 in neoplasia. Ann Clin Lab Sci. 2000;30:3–21.

    CAS  PubMed  Google Scholar 

  • Fox SB, Moghaddam A, Westwood M, Turley H, Bicknell R, Gatter KC, Harris AL. Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in normal tissues: an immunohistochemical study. J Pathol. 1995;176:183–90.

    CAS  PubMed  Google Scholar 

  • Friedrich M. Analysis of the DNA “mismatch-repair” enzyme human mut-S-homologon-2 in endometrial cancer on protein- and RNA-level. Eur J Gynaecol Oncol. 2000;21:273–7.

    CAS  PubMed  Google Scholar 

  • Frumovitz M, Sood AK. Vascular endothelial growth factor (VEGF) pathway as a therapeutic target in gynecologic malignancies. Gynecol Oncol. 2007;104:768–78.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fujimoto J, Ichigo S, Sakaguchi H, Hirose R, Tamaya T. Expression of platelet-derived endothelial cell growth factor and its mRNA in uterine endometrium during the menstrual cycle. Mol Hum Reprod. 1998;4:509–13.

    CAS  PubMed  Google Scholar 

  • Fujimoto J, Sato E, Alam SM, Jahan I, Toyoki H, Hong BL, Sakaguchi H, Tamaya T. Plausible linkage of hypoxia-inducible factor (HIF) in uterine endometrial cancers. Oncology. 2006;71:95–101.

    CAS  PubMed  Google Scholar 

  • Gassel AM, Backe J, Krebs S, Schon S, Caffier H, Muller-Hermelink HK. Endometrial carcinoma: immunohistochemically detected proliferation index is a prognosticator of long-term outcome. J Clin Pathol. 1998;51:25–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Giambernardi TA, Grant GM, Taylor GP, Hay RJ, Maher VM, McCormick JJ, Klebe RJ. Overview of matrix metalloproteinase expression in cultured human cells. Matrix Biol. 1998;16:483–96.

    CAS  PubMed  Google Scholar 

  • Guidi AJ, Abu-Jawdeh G, Tognazzi K, Dvorak HF, Brown LF. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in endometrial carcinoma. Cancer. 1996;78:454–60.

    CAS  PubMed  Google Scholar 

  • Guset G, Costi S, Lazar E, Dema A, Cornianu M, Vernic C, Paiusan L. Expression of vascular endothelial growth factor (VEGF) and assessment of microvascular density with CD34 as prognostic markers for endometrial carcinoma. Rom J Morphol Embryol. 2010;51:677–82.

    CAS  PubMed  Google Scholar 

  • Hirai M, Nakagawara A, Oosaki T, Hayashi Y, Hirono M, Yoshihara T. Expression of vascular endothelial growth factors (VEGF-A/VEGF-1 and VEGF-C/VEGF-2) in postmenopausal uterine endometrial carcinoma. Gynecol Oncol. 2001;80:181–8.

    CAS  PubMed  Google Scholar 

  • Hirai Y, Banno K, Suzuki M, Ichikawa Y, Udagawa Y, Sugano K, Miki Y. Molecular epidemiological and mutational analysis of DNA mismatch repair (MMR) genes in endometrial cancer patients with HNPCC-associated familial predisposition to cancer. Cancer Sci. 2008;99:1715–9.

    CAS  PubMed  Google Scholar 

  • Honkavuori M, Talvensaari-Mattila A, Soini Y, Turpeenniemi-Hujanen T, Santala M. MMP-2 expression associates with CA 125 and clinical course in endometrial carcinoma. Gynecol Oncol. 2007;104:217–21.

    CAS  PubMed  Google Scholar 

  • Horree N, Gort EH, van der Groep P, Heintz AP, Vooijs M, van Diest PJ. Hypoxia-inducible factor 1 alpha is essential for hypoxic p27 induction in endometrioid endometrial carcinoma. J Pathol. 2008;214:38–45.

    CAS  PubMed  Google Scholar 

  • Huszar M, Pfeifer M, Schirmer U, Kiefel H, Konecny GE, Ben-Arie A, Edler L, Munch M, Muller-Holzner E, Jerabek-Klestil S, et al. Up-regulation of L1CAM is linked to loss of hormone receptors and E-cadherin in aggressive subtypes of endometrial carcinomas. J Pathol. 2010;220:551–61.

    CAS  PubMed  Google Scholar 

  • Ishikawa F, Miyazono K, Hellman U, Drexler H, Wernstedt C, Hagiwara K, Usuki K, Takaku F, Risau W, Heldin C-H. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature. 1989;338:557–62.

    CAS  PubMed  Google Scholar 

  • Kanamori Y, Kigawa J, Itamochi H, Sultana H, Suzuki M, Ohwada M, Kamura T, Sugiyama T, Kikuchi Y, Kita T, et al. PTEN expression is associated with prognosis for patients with advanced endometrial carcinoma undergoing postoperative chemotherapy. Int J Cancer. 2002;100:686–9.

    CAS  PubMed  Google Scholar 

  • Kiefel H, Bondong S, Hazin J, Ridinger J, Schirmer U, Riedle S, Altevogt P. L1CAM: a major driver for tumor cell invasion and motility. Cell Adh Migr. 2012;6:374–84.

    PubMed Central  PubMed  Google Scholar 

  • Kohlberger P, Loesch A, Koelbl H, Breitenecker G, Kainz C, Gitsch G. Prognostic value of immunohistochemically detected HER-2/neu oncoprotein in endometrial cancer. Cancer Lett. 1996;98:151–5.

    CAS  PubMed  Google Scholar 

  • Kokka F, Brockbank E, Oram D, Gallagher C, Bryant A. Hormonal therapy in advanced or recurrent endometrial cancer. Cochrane Database Syst Rev. 2010;CD007926

    Google Scholar 

  • Konstantinova D, Kaneva R, Dimitrov R, Savov A, Ivanov S, Dyankova T, Kremensky I, Mitev V. Rare mutations in the PIK3CA gene contribute to aggressive endometrial cancer. DNA Cell Biol. 2010;29:65–70.

    CAS  PubMed  Google Scholar 

  • Korsmeyer SJ. Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood. 1992;80:879–86.

    CAS  PubMed  Google Scholar 

  • Koukourakis MI, Giatromanolaki A, Sivridis E, Fezoulidis I. Cancer vascularization: implications in radiotherapy? Int J Radiat Oncol Biol Phys. 2000;48:545–53.

    CAS  PubMed  Google Scholar 

  • Landen Jr CN, Mathur SP, Richardson MS, Creasman WT. Expression of cyclooxygenase-2 in cervical, endometrial, and ovarian malignancies. Am J Obstet Gynecol. 2003;188:1174–6.

    CAS  PubMed  Google Scholar 

  • Lax SF, Kurman RJ. A dualistic model for endometrial carcinogenesis based on immunohistochemical and molecular genetic analyses. Verh Dtsch Ges Pathol. 1997;81:228–32.

    CAS  PubMed  Google Scholar 

  • Liggett Jr WH, Sidransky D. Role of the p16 tumor suppressor gene in cancer. J Clin Oncol. 1998;16:1197–206.

    CAS  PubMed  Google Scholar 

  • Liu FS. Molecular carcinogenesis of endometrial cancer. Taiwan J Obstet Gynecol. 2007;46:26–32.

    CAS  PubMed  Google Scholar 

  • Liu T, Du X, Sheng X. Gene expression changes after ionizing radiation in endothelial cells derived from human endometrial cancer-preliminary outcomes. Arch Gynecol Obstet. 2014;289:1315–23.

    CAS  PubMed  Google Scholar 

  • Lukes AS, Kohler MF, Pieper CF, Kerns BJ, Bentley R, Rodriguez GC, Soper JT, Clarke-Pearson DL, Bast Jr RC, Berchuck A. Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer. Cancer. 1994;73:2380–5.

    CAS  PubMed  Google Scholar 

  • Lynch HT, Smyrk T, Lynch JF. Overview of natural history, pathology, molecular genetics and management of HNPCC (Lynch syndrome). Int J Cancer. 1996;69:38–43.

    CAS  PubMed  Google Scholar 

  • Maxwell GL, Risinger JI, Gumbs C, Shaw H, Bentley RC, Barrett JC, Berchuck A, Futreal PA. Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias. Cancer Res. 1998;58:2500–3.

    CAS  PubMed  Google Scholar 

  • McCulloch E, Minden M. The cell surface receptor encoded by the proto-oncogene KIT and its ligand. In: Leukemia: advances in research and treatment. New York: Springer; 1993. p. 45–77.

    Google Scholar 

  • Miyadera K, Sumizawa T, Haraguchi M, Yoshida H, Konstanty W, Yamada Y, S-i A. Role of thymidine phosphorylase activity in the angiogenic effect of platelet-derived endothelial cell growth factor/thymidine phosphorylase. Cancer Res. 1995;55:1687–90.

    CAS  PubMed  Google Scholar 

  • Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Reed JC. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 1994;9:1799–805.

    CAS  PubMed  Google Scholar 

  • Moghaddam A, Zhang H-T, Fan T, Hu D-E, Lees VC, Turley H, Fox SB, Gatter KC, Harris AL, Bicknell R. Thymidine phosphorylase is angiogenic and promotes tumor growth. Proc Natl Acad Sci. 1995;92:998–1002.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Morrison C, Zanagnolo V, Ramirez N, Cohn DE, Kelbick N, Copeland L, Maxwell GL, Fowler JM. HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients. J Clin Oncol. 2006;24:2376–85.

    CAS  PubMed  Google Scholar 

  • Mutter GL. Pten, a protean tumor suppressor. Am J Pathol. 2001;158:1895–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nielsen AL, Nyholm HC. Proliferative activity as revealed by Ki-67 in uterine adenocarcinoma of endometrioid type: comparison of tumours from patients with and without previous oestrogen therapy. J Pathol. 1993;171:199–205.

    CAS  PubMed  Google Scholar 

  • No JH, Jeon YT, Park IA, Kang D, Kim JW, Park NH, Kang SB, Song YS. Expression of mTOR protein and its clinical significance in endometrial cancer. Med Sci Monit. 2009;15:BR301–5.

    PubMed  Google Scholar 

  • Oda K, Stokoe D, Taketani Y, McCormick F. High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res. 2005;65:10669–73.

    CAS  PubMed  Google Scholar 

  • Oreskovic S, Babic D, Kalafatic D, Barisic D, Beketic-Oreskovic L. A significance of immunohistochemical determination of steroid receptors, cell proliferation factor Ki-67 and protein p53 in endometrial carcinoma. Gynecol Oncol. 2004;93:34–40.

    CAS  PubMed  Google Scholar 

  • Otsuki Y, Misaki O, Sugimoto O, Ito Y, Tsujimoto Y, Akao Y. Cyclic bcl-2 gene expression in human uterine endometrium during menstrual cycle. Lancet. 1994;344:28–9.

    CAS  PubMed  Google Scholar 

  • Ozbudak IH, Karaveli S, Simsek T, Erdogan G, Pestereli E. Neoangiogenesis and expression of hypoxia-inducible factor 1alpha, vascular endothelial growth factor, and glucose transporter-1 in endometrioid type endometrium adenocarcinomas. Gynecol Oncol. 2008;108:603–8.

    CAS  PubMed  Google Scholar 

  • Page-McCaw A, Ewald AJ, Werb Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol. 2007;8:221–33.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pansare V, Munkarah AR, Schimp V, Haitham Arabi M, Saed GM, Morris RT, Ali-Fehmi R. Increased expression of hypoxia-inducible factor 1alpha in type I and type II endometrial carcinomas. Mod Pathol. 2007;20:35–43.

    CAS  PubMed  Google Scholar 

  • Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    PubMed  Google Scholar 

  • Pfisterer J, Kommoss F, Sauerbrei W, Rendl I, Kiechle M, Kleine W, Pfleiderer A. Prognostic value of DNA ploidy and S-phase fraction in stage I endometrial carcinoma. Gynecol Oncol 1995;58(2):149–56.

    CAS  PubMed  Google Scholar 

  • Pisani AL, Barbuto DA, Chen D, Ramos L, Lagasse LD, Karlan BY. HER-2/neu, p53, and DNA analyses as prognosticators for survival in endometrial carcinoma. Obstet Gynecol. 1995;85:729–34.

    CAS  PubMed  Google Scholar 

  • Prat J, Gallardo A, Cuatrecasas M, Catasus L. Endometrial carcinoma: pathology and genetics. Pathology. 2007;39:72–87.

    CAS  PubMed  Google Scholar 

  • Rubin CI, Atweh GF. The role of stathmin in the regulation of the cell cycle. J Cell Biochem. 2004;93:242–50.

    CAS  PubMed  Google Scholar 

  • Sakuragi N, Salah-eldin AE, Watari H, Itoh T, Inoue S, Moriuchi T, Fujimoto S. Bax, Bcl-2, and p53 expression in endometrial cancer. Gynecol Oncol. 2002;86:288–96.

    CAS  PubMed  Google Scholar 

  • Salvesen HB, Akslen LA. Molecular pathogenesis and prognostic factors in endometrial carcinoma. APMIS. 2002;110:673–89.

    CAS  PubMed  Google Scholar 

  • Salvesen HB, Das S, Akslen LA. 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. 2000;6:153–9.

    CAS  PubMed  Google Scholar 

  • Salvesen HB, Carter SL, Mannelqvist M, Dutt A, Getz G, Stefansson IM, Raeder MB, Sos ML, Engelsen IB, Trovik J, et al. Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation. Proc Natl Acad Sci U S A. 2009;106:4834–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Salvesen HB, Haldorsen IS, Trovik J. Markers for individualised therapy in endometrial carcinoma. Lancet Oncol. 2012;13:e353–61.

    PubMed  Google Scholar 

  • Sanseverino F, Santopietro R, Torricelli M, D'Andrilli G, Russo G, Cevenini G, Bovicelli A, Leoncini L, Scambia G, Petraglia F. pRb2/p130 and VEGF expression in endometrial carcinoma in relation to angiogenesis and histopathologic tumor grade. Cancer Biol Ther. 2006;5:84–8.

    CAS  PubMed  Google Scholar 

  • Schafer MK, Altevogt P. L1CAM malfunction in the nervous system and human carcinomas. Cell Mol Life Sci. 2010;67:2425–37.

    PubMed  Google Scholar 

  • Schropfer A, Kammerer U, Kapp M, Dietl J, Feix S, Anacker J. Expression pattern of matrix metalloproteinases in human gynecological cancer cell lines. BMC Cancer. 2010;10:553.

    PubMed Central  PubMed  Google Scholar 

  • Seeber LM, Horree N, van der Groep P, van der Wall E, Verheijen RH, van Diest PJ. Necrosis related HIF-1alpha expression predicts prognosis in patients with endometrioid endometrial carcinoma. BMC Cancer. 2010;10:307.

    PubMed Central  PubMed  Google Scholar 

  • Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature. 2006;441:424–30.

    CAS  PubMed  Google Scholar 

  • Sheahan K, O'brien M, Burke B, Dervan P, O'keane J, Gottlieb L, Zamcheck N. Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies. Am J Clin Pathol. 1990;94:157.

    CAS  PubMed  Google Scholar 

  • Slomovitz BM, Broaddus RR, Burke TW, Sneige N, Soliman PT, Wu W, Sun CC, Munsell MF, Gershenson DM, Lu KH. Her-2/neu overexpression and amplification in uterine papillary serous carcinoma. J Clin Oncol. 2004;22:3126–32.

    CAS  PubMed  Google Scholar 

  • Spatz A, Borg C, Feunteun J. X-chromosome genetics and human cancer. Nat Rev Cancer. 2004;4:617–29.

    CAS  PubMed  Google Scholar 

  • Srijaipracharoen S, Tangjitgamol S, Tanvanich S, Manusirivithaya S, Khunnarong J, Thavaramara T, Leelahakorn S, Pataradool K. Expression of ER, PR, and Her-2/neu in endometrial cancer: a clinicopathological study. Asian Pac J Cancer Prev. 2010;11:215–20.

    PubMed  Google Scholar 

  • Strang P, Nordstom B, Nilsson S, Bergstrom R, Tribukait B. Mutant p53 protein as a predictor of survival in endometrial carcinoma. Eur J Cancer. 1996;32A(4):598–602.

    CAS  PubMed  Google Scholar 

  • Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol. 2001;17:463–516.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sumizawa T, Furukawa T, Haraguchi M, Yoshimura A, Takeyasu A, Ishizawa M, Yamada Y, S-i A. Thymidine phosphorylase activity associated with platelet-derived endothelial cell growth factor. J Biochem. 1993;114:9–14.

    CAS  PubMed  Google Scholar 

  • Talvensaari-Mattila A, Santala M, Soini Y, Turpeenniemi-Hujanen T. Prognostic value of matrix metalloproteinase-2 (MMP-2) expression in endometrial endometrioid adenocarcinoma. Anticancer Res. 2005a;25:4101–5.

    CAS  PubMed  Google Scholar 

  • Talvensaari-Mattila A, Soini Y, Santala M. VEGF and its receptors (flt-1 and KDR/flk-1) as prognostic indicators in endometrial carcinoma. Tumor Biol. 2005b;26:81–7.

    CAS  Google Scholar 

  • Thompson J, Mössinger S, Reichardt V, Engels U, Beauchemin N, Kommoss F, Von Kleist S, Zimmermann W. A polymerase-chain-reaction assay for the specific identification of transcripts encoded by individual carcinoembryonic antigen (CEA)-gene-family members. Int J Cancer. 1993;55:311–9.

    CAS  PubMed  Google Scholar 

  • Trovik J, Wik E, Stefansson IM, Marcickiewicz J, Tingulstad S, Staff AC, Njolstad TS, MoMaTec Study Group, Vandenput I, Amant F, et al. Stathmin overexpression identifies high-risk patients and lymph node metastasis in endometrial cancer. Clin Cancer Res. 2011;17:3368–77.

    CAS  PubMed  Google Scholar 

  • Trovik J, Wik E, Werner HM, Krakstad C, Helland H, Vandenput I, Njolstad TS, Stefansson IM, Marcickiewicz J, Tingulstad S, et al. Hormone receptor loss in endometrial carcinoma curettage predicts lymph node metastasis and poor outcome in prospective multicentre trial. Eur J Cancer. 2013;49:3431–41.

    CAS  PubMed  Google Scholar 

  • Tsikouras P, Bouchlariotou S, Vrachnis N, Dafopoulos A, Galazios G, Csorba R, von Tempelhoff GF. Endometrial cancer: molecular and therapeutic aspects. Eur J Obstet Gynecol Reprod Biol. 2013;169:1–9.

    CAS  PubMed  Google Scholar 

  • Ushijima K. Current status of gynecologic cancer in Japan. J Gynecol Oncol. 2009;20:67–71.

    PubMed Central  PubMed  Google Scholar 

  • Vandenput I, Debiec-Rychter M, Capoen A, Verbist G, Vergote I, Moerman P, Amant F. Kit gene in endometrial carcinoma: an immunohistochemical and mutational analysis. Int J Gynecol Cancer. 2011;21:203–5.

    PubMed  Google Scholar 

  • Wang L, Felix JC, Lee JL, Tan PY, Tourgeman DE, O’Meara AT, Amezcua CA. The proto-oncogene c-kit is expressed in leiomyosarcomas of the uterus. Gynecol Oncol. 2003;90:402–6.

    CAS  PubMed  Google Scholar 

  • Wright JD, Barrena Medel NI, Sehouli J, Fujiwara K, Herzog TJ. Contemporary management of endometrial cancer. Lancet. 2012;379:1352–60.

    PubMed  Google Scholar 

  • Yilmaz E, Celik O, Simsek Y, Turkcuoglu I, Celik E, Gül M, Hascalik S, Aydin E. c-Kit proto-oncogene expression in endometrial hyperplasia and endometrial cancer. Arch Gynecol Obstet. 2012;286:197–200.

    CAS  PubMed  Google Scholar 

  • Yoshida Y, Kurokawa T, Horiuchi Y, Sawamura Y, Shinagawa A, Kotsuji F. Localisation of phosphorylated mTOR expression is critical to tumour progression and outcomes in patients with endometrial cancer. Eur J Cancer. 2010;46:3445–52.

    CAS  PubMed  Google Scholar 

  • Yuan R, Kay A, Berg WJ, Lebwohl D. Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy. J Hematol Oncol. 2009;2:45.

    PubMed Central  PubMed  Google Scholar 

  • Zeimet AG, Reimer D, Huszar M, Winterhoff B, Puistola U, Azim SA, Muller-Holzner E, Ben-Arie A, van Kempen LC, Petru E, et al. L1CAM in early-stage type I endometrial cancer: results of a large multicenter evaluation. J Natl Cancer Inst. 2013;105:1142–50.

    PubMed  Google Scholar 

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  1. Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, #388-1 Poongnap-2 dong, 138-736, Seoul, South Korea

    Joo-Hyun Nam, Jeong-Yeol Park, Min-Hyun Baek, Ji-Hyun Han, Woo-Suk Han & A-Ra Ko

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  1. Joo-Hyun Nam
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  2. Jeong-Yeol Park
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  3. Min-Hyun Baek
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  4. Ji-Hyun Han
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  5. Woo-Suk Han
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  6. A-Ra Ko
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Correspondence to Joo-Hyun Nam .

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  1. Department of Nutrition and Dietetics Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine King’s College London, London, United Kingdom

    Victor R. Preedy

  2. Department of Biomedical Sciences Faculty of Science and Technology, University of Westminster, London, United Kingdom

    Vinood B. Patel

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© 2014 Springer Science+Business Media Dordrecht

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Nam, JH., Park, JY., Baek, MH., Han, JH., Han, WS., Ko, AR. (2014). Immunohistochemistry as Biomarker Platform in Endometrial Cancer. In: Preedy, V., Patel, V. (eds) Biomarkers in Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7744-6_42-1

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  • DOI: https://doi.org/10.1007/978-94-007-7744-6_42-1

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  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-7744-6

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

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