| Peer-Reviewed

Comparison of LPA1 and LPA2 Receptor Expression with Proliferative and Prognostic Factors in Endometroid Carcinomas and Endometrial Hyperplasias

Received: 16 June 2014    Accepted: 1 July 2014    Published: 10 July 2014
Views:       Downloads:
Abstract

Objective: In this study we aimed to evaluate the staining patterns of lysophosphatidic acid in endometrial carcinomas(EC) and endometrial hyperplasias(EH). Materials and Method: Sixty diagnostic cases were included in this study in order to evaluate the staining patterns of lysophosphatidic acid in EC and EH. EC was diagnosed in 20 of the cases, EH with atypia was present in 20 and EH without atypia was evident in 20 of the cases. Patients staged according to FİGO(International Federation of Gynecology and Obstetrics,2014). After performing the new sections on each of these cases, 55 routine Hematoxylin and eosin staining was repeated, sections of chosen diagnostic blocks were stained immune histologically with LPA1(Lysophosphatidic acid 1), LPA(Lysophosphatidic acid 2), MMP-2(Matrix metalloproteinase 2) and Ki-67 antibodies. Results: According to the data obtained, LPA1 showed most intense staining in cases with EH without atypia, however endometrioid type endometrial carcinoma (EEC) cases had the levels very close to this. Furthermore, it was found that there was a reverse correlation between LPA1 staining and histological grade in cases with EEC. It was noted that highest level of LPA2 staining was in cases that had EH with atypia where as lowest level was seen in cases with EEC cases. No relationship between LPA2 and the grade in cases with EEC. It was found that MMP-2 increased linearly with the histological grade in cases with EEC. Correlation tests done among LPA1, LPA2 and MMP-2 antibodies revealed moderate degree of relation only between LAP1 and MMP-2 scores in cases with EEC. No significant relation could be shown in correlation test done between LPA1 and LPA2 and Ki-67, a marker for proliferation index. Conclusion: When correlation of LPA1, LPA2 and MMP-2 H scores with stages of EEC cases was taken into account, the average LPA1 H score was higher in stage 1, while H score averages of LPA2 and MMP-2 H scores were higher in stage 2+3 tumors, however these differences were not statistically significant.

Published in American Journal of Clinical and Experimental Medicine (Volume 2, Issue 4)
DOI 10.11648/j.ajcem.20140204.12
Page(s) 64-69
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

LPA1-2, MMP-2 Immunohistochemistry, Endometrial Carcinoma, Endometrial Hyperplasia, FİGO, Endometrioid Carcinoma

References
[1] Lomnytska M, Becker S, Gemoll T. Impact of genomic stability on protein expression in endometrioid endometrial cancer. Br J Cancer. 2012 March 27; 106(7): 1297–1305. . Published online 2012 March 13 .doi :10. 1038 /bjc. 2012.67
[2] O’Hara A,Bell D. The genomics and genetics of endometrial cancer Adv Genomics Genet. Author manuscript; available in PMC 2012 August 9. Published in final edited form as: Adv Genomics Genet. 2012 March; 2012(2): 33–47. doi: 10.2147/AGG.S28953
[3] Felix A,Weissfeld J,Stone R,Bowser R. Factors associated with Type I and Type II endometrial cancer. Cancer Causes Control. 1851–1856. Published online 2010 July 14. doi: 10.1007/s10552-010-9612-8
[4] Mark E,Sherman A. Theories of Endometrial Carcinogenesis: A Multidisciplinary Approach Mod Pathol 2000;13:295–308.
[5] Ioffe OB,Papadimitriou JC,Drachenberg CB. Correlation of proliferation indices, appopitosis and related oncogene expression (bcl-2 and c-erbB-2) and p53 in proliferative, hyperplastic and malignant endometrium. Hum Pathol 1998;29(10):1150–9.
[6] Lynch H, Casey J, Hereditary Ovarian Cancer: Molecular Genetics, Pathology, Management and Heterogeneity.2009 April; 3(2): 97–137. Published online 2009 February 21. doi: 10.1016/j.molonc.2009.02.004
[7] Norasate Samarnthai, Kevin Hall, I-Tien Yeh Molecular Profiling of Endometrial Malignancies. Obstet Gynecol Int. 2010; 2010: 162363. Published online 2010 March 28. doi: 10.1155/2010/162363
[8] Hendrickson MR,Longacre TA,Kempson RL. The uterin corpus. In: Mııls SE, Carter D, Reuter VE, Greenson JK, Stoler MH, Oberman HA. Stenberg’s diagnostic surgical Pathology. 4th. Ed.Philadelphia: Lipincott Williams & Wilkins; 2004.p.2435–43.
[9] Rodriguez A.F, Folpe A.L, Pathology of Peripheral Nerve Sheath Tumors: Diagnostic Overview and Update on Selected Diagnostic Problem.Acta Neuropathol. 2012 March; 123(3): 295–319. Published online 2012 February 12. doi: 10.1007/s00401-012-0954
[10] Melissa A. Merritt, Daniel W. Molecular Pathogenesis of Endometrial and Ovarian Cancer .PMC 2013 November 11. 2010; 9(0): 10.3233/CBM-2011-0167 . doi : 10 .3233 /CBM-2011-0167
[11] Kurman R, Shih I .The Origin and Pathogenesis of Epithelial Ovarian Cancer- a Proposed Unifying Theory. 2010 March; 34(3): 433 443. Doi : 10 .1097/ PAS.
[12] Tan M, Strunc E, Scholzen T, Gerdes J, Vollmer G. Extracelluler matrix regulates Steady state Mrna levels of the proliferation associated protein Ki-67 in endometrial cancer cells.Cancer Letters 1999;140:145-52.
[13] Ambros RA. Simple hyperplasia of the endometrium: An evoluation of proliferative activitiy Ki–67 immunostaining. Int J GynPathol 2000;19:206–11.
[14] Vaskiuvuo TE, Stenback F, Karhumaa P. Apopitosis and apoptosis-releated proteins in human endometrium. Molecular and Cellular Endocrinology 2000;165:75–83.
[15] Matsomoto Y,Iwasaka T, Yamasaki F,Sugimori H. Apoptosis and Ki-67 expression in adenomyotic lesions and in the corresponding eutopic endometrium. ObstetGynecol 1999;94:71–7.
[16] Salvesen HB, Iversan OE, Akslen LA. Identification of high risk patients by assessment of nuclear Ki-67 expression in a prospective study of endometrial carcinomas. Clin Cancer Res 1998;4:2779–85.
[17] An S, Dickens MA, Bleu T, Hallmark OG, Goetzl EJ. Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid.BiochemBiophys Res Commun 1997;231:619–22.
[18] Lee MJ, Van Brocklyn JR, Thangada S, Liu CH, Hand AR, Menzeleev R et al. Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science (Wash DC) 1998;279:1552-5.
[19] Contos JJ, Ishii I, Fukushima N, Kingsbury MA, Ye X, Kawamura S et al. Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: Signaling deficits without obvious phenotypic abnormality attributable to lpa(2). Mol Cell Bio 2002;22:6921–29.
[20] Inoue M, Rashid MH, Fujita R, Contos JJ, Chun J, Ueda H. Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nat Med 2004;10:712–8.
[21] Castro A, Johnson MC, Ando M, Cortinez A, Gabler F, Vega M. Role of nitric oxide and bcl–2 family genes in the regulation of human endometrial apopitosis. FerSter 2002;78(3):587–95.
[22] Prat J. Prognostic parameters of endometrial carcinoma. Hum Pathol 2004;35(6):649–62.
[23] Maneschi M, Maneschi F, Geraci P. Surgical pathological staging of endometrial adenocarcinoma and results of treatment. Eur J GynecolOncol 1992;45:142–6.
[24] Grushko T.A, Filiaci V.L, Mundt A.J, Ridderstråle K. An Exploratory Analysis of HER-2 Amplification and Overexpression in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study.Gynecol Oncol. 2008 January; 108(1): 3–9. Published online 2007 October 18. doi: 10.1016/j.ygyno.2007.09.007
[25] Aromatase in human endometrial carcinoma and hyperplasia. Immunohistochemical, in situ hybridization, and biochemical studies Aromatase in human endometrial carcinoma and hyperplasia. Immunohistochemical, in situ hybridization, and biochemical studie Zaino JR, Kurman RJ, Herbold D. The signifiance of squamous diferentiation in endometrial carcinoma. Cancer 1991;68:2293–302.
[26] Dai S, Toshiaki W, Junken A. Aberrant expression of lysophosphatidic acid (LPA) receptors in human colorectal cancer. Laboratory Investigation. 2004: 84;1352–62.
[27] Schulte KM, Beyer A, Köhrer K, Oberhauser S, Röher HD. Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer. Int J Cancer 2001;92:249–56.
[28] Joji K, Dai S, Akihiro S. Over-expression of lysophosphatidic acid receptor-2 in human invasive ductal carcinoma. Breast Cancer Res 2004;6:640-6.
[29] Ma D, Chen Z., Nero C, P. Patel K.Somatic Deletions of the PolyA Tract in the 3′ Untranslated Region of Epidermal Growth Factor Receptor Are Common in Microsatellite Instability–High Endometrial and Colorectal Carcinomas.Arch Pathol Lab Med. Author manuscript; 2012 May; 136(5): 510–516. doi: 10.5858/arpa.2010-0638-OA
[30] Guo W, Chen G, Zhu C, Wang H. Expression of matrix metalloproteinase–2, -9 and it’s tissue inhibitor–1,-2 in endometrial carcinoma. Zhonghua Fu Chan KeZaZhi 2002;37:604–7.
[31] Graesslin O, Cortez A, Fauvet R. Metalloproteinase -2, -7 and -9 and tissue inhibitor of metalloproteinase- 1 and -2 expression in normal, hyperplastic and neoplastic endometrium: a clinical- pathological correlation study. Ann Oncol 2006;17(4): 637–45.
[32] Langosch KM, Bamberger AM, Goemann C, Rössing E, Rieck G, Kelp B et al. Expression of cell-cycle regulatory proteins in endometrial carcinomas: correlations with hormone receptor status and clinicopathologic parameters. J Cancer Res Clin Oncol 2001;127:537-44.
[33] Morsi HM, Leers MPG, Jager W, Björklund V, Radespiel-Tröger M, Kabarity HE et al.The patterns of expression of an apopitosis related CK–18 neoepitope, the bcl–2 protoonkogene, and the Ki–67 proliferation marker in the normal, hyperplastic and malignant endometrium. Int J GynPathol 2000;19:118–26.
[34] Salvesen HB, Iversen OE, Akslen LA. Prognostic significance of angiogenesis and Ki–67,p–53, and p21 expression: A population based endometrial carcinoma study. J ClinOncol 1999;17:1382–90.
Cite This Article
  • APA Style

    Ayşegül Kaynar, Serdar Yanık, Ayşe Neslin Akkoca, Raziye Kurt, Ozan Turgut, et al. (2014). Comparison of LPA1 and LPA2 Receptor Expression with Proliferative and Prognostic Factors in Endometroid Carcinomas and Endometrial Hyperplasias. American Journal of Clinical and Experimental Medicine, 2(4), 64-69. https://doi.org/10.11648/j.ajcem.20140204.12

    Copy | Download

    ACS Style

    Ayşegül Kaynar; Serdar Yanık; Ayşe Neslin Akkoca; Raziye Kurt; Ozan Turgut, et al. Comparison of LPA1 and LPA2 Receptor Expression with Proliferative and Prognostic Factors in Endometroid Carcinomas and Endometrial Hyperplasias. Am. J. Clin. Exp. Med. 2014, 2(4), 64-69. doi: 10.11648/j.ajcem.20140204.12

    Copy | Download

    AMA Style

    Ayşegül Kaynar, Serdar Yanık, Ayşe Neslin Akkoca, Raziye Kurt, Ozan Turgut, et al. Comparison of LPA1 and LPA2 Receptor Expression with Proliferative and Prognostic Factors in Endometroid Carcinomas and Endometrial Hyperplasias. Am J Clin Exp Med. 2014;2(4):64-69. doi: 10.11648/j.ajcem.20140204.12

    Copy | Download

  • @article{10.11648/j.ajcem.20140204.12,
      author = {Ayşegül Kaynar and Serdar Yanık and Ayşe Neslin Akkoca and Raziye Kurt and Ozan Turgut and Zeynep Tuba Özdemir and Nurdan Tatar and Ufuk Usta},
      title = {Comparison of LPA1 and LPA2 Receptor Expression with Proliferative and Prognostic Factors in Endometroid Carcinomas and Endometrial Hyperplasias},
      journal = {American Journal of Clinical and Experimental Medicine},
      volume = {2},
      number = {4},
      pages = {64-69},
      doi = {10.11648/j.ajcem.20140204.12},
      url = {https://doi.org/10.11648/j.ajcem.20140204.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20140204.12},
      abstract = {Objective: In this study we aimed to evaluate the staining patterns of lysophosphatidic acid in endometrial carcinomas(EC) and endometrial hyperplasias(EH). Materials and Method: Sixty diagnostic cases were included in this study in order to evaluate the staining patterns of lysophosphatidic acid in EC and EH. EC was diagnosed in 20 of the cases, EH with atypia was present in 20 and EH without atypia was evident in 20 of the cases. Patients staged according to FİGO(International Federation of Gynecology and Obstetrics,2014). After performing the new sections on each of these cases, 55 routine Hematoxylin and eosin staining was repeated, sections of chosen diagnostic blocks were stained immune histologically with  LPA1(Lysophosphatidic acid 1), LPA(Lysophosphatidic acid 2), MMP-2(Matrix metalloproteinase 2) and Ki-67 antibodies. Results: According to the data obtained, LPA1 showed most intense staining in cases with EH without atypia, however endometrioid type endometrial carcinoma (EEC) cases had the levels very close to this. Furthermore, it was found that there was a reverse correlation between LPA1 staining and histological grade in cases with EEC. It was noted that highest level of LPA2 staining was in cases that had EH with atypia where as lowest level was seen in cases with EEC cases. No relationship between LPA2 and the grade in cases with EEC. It was found that MMP-2 increased linearly with the histological grade in cases with EEC. Correlation tests done among LPA1, LPA2 and MMP-2 antibodies revealed moderate degree of relation only between LAP1 and MMP-2 scores in cases with EEC. No significant relation could be shown in correlation test done between LPA1 and LPA2 and Ki-67, a marker for proliferation index. Conclusion: When correlation of LPA1, LPA2 and MMP-2 H scores with stages of EEC cases was taken into account, the average LPA1 H score was higher in stage 1, while H score averages of LPA2 and MMP-2 H scores were higher in stage 2+3 tumors, however these differences were not statistically significant.},
     year = {2014}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Comparison of LPA1 and LPA2 Receptor Expression with Proliferative and Prognostic Factors in Endometroid Carcinomas and Endometrial Hyperplasias
    AU  - Ayşegül Kaynar
    AU  - Serdar Yanık
    AU  - Ayşe Neslin Akkoca
    AU  - Raziye Kurt
    AU  - Ozan Turgut
    AU  - Zeynep Tuba Özdemir
    AU  - Nurdan Tatar
    AU  - Ufuk Usta
    Y1  - 2014/07/10
    PY  - 2014
    N1  - https://doi.org/10.11648/j.ajcem.20140204.12
    DO  - 10.11648/j.ajcem.20140204.12
    T2  - American Journal of Clinical and Experimental Medicine
    JF  - American Journal of Clinical and Experimental Medicine
    JO  - American Journal of Clinical and Experimental Medicine
    SP  - 64
    EP  - 69
    PB  - Science Publishing Group
    SN  - 2330-8133
    UR  - https://doi.org/10.11648/j.ajcem.20140204.12
    AB  - Objective: In this study we aimed to evaluate the staining patterns of lysophosphatidic acid in endometrial carcinomas(EC) and endometrial hyperplasias(EH). Materials and Method: Sixty diagnostic cases were included in this study in order to evaluate the staining patterns of lysophosphatidic acid in EC and EH. EC was diagnosed in 20 of the cases, EH with atypia was present in 20 and EH without atypia was evident in 20 of the cases. Patients staged according to FİGO(International Federation of Gynecology and Obstetrics,2014). After performing the new sections on each of these cases, 55 routine Hematoxylin and eosin staining was repeated, sections of chosen diagnostic blocks were stained immune histologically with  LPA1(Lysophosphatidic acid 1), LPA(Lysophosphatidic acid 2), MMP-2(Matrix metalloproteinase 2) and Ki-67 antibodies. Results: According to the data obtained, LPA1 showed most intense staining in cases with EH without atypia, however endometrioid type endometrial carcinoma (EEC) cases had the levels very close to this. Furthermore, it was found that there was a reverse correlation between LPA1 staining and histological grade in cases with EEC. It was noted that highest level of LPA2 staining was in cases that had EH with atypia where as lowest level was seen in cases with EEC cases. No relationship between LPA2 and the grade in cases with EEC. It was found that MMP-2 increased linearly with the histological grade in cases with EEC. Correlation tests done among LPA1, LPA2 and MMP-2 antibodies revealed moderate degree of relation only between LAP1 and MMP-2 scores in cases with EEC. No significant relation could be shown in correlation test done between LPA1 and LPA2 and Ki-67, a marker for proliferation index. Conclusion: When correlation of LPA1, LPA2 and MMP-2 H scores with stages of EEC cases was taken into account, the average LPA1 H score was higher in stage 1, while H score averages of LPA2 and MMP-2 H scores were higher in stage 2+3 tumors, however these differences were not statistically significant.
    VL  - 2
    IS  - 4
    ER  - 

    Copy | Download

Author Information
  • Department of Obstetrics and Gynecology, Mustafa Kemal University, Medical School, Hatay, Turkey

  • Department of Obstetrics and Gynecology, ?skenderun State Hospital, Hatay, Turkey

  • Department of Patology, ?skenderun State Hospital, Hatay, Turkey

  • Department of Patology, Trakya University Medical School, Edirne, Turkey

  • Sections