Download PDF
Rev Bras Ginecol Obstet 2016; 38(05): 253-262
DOI: 10.1055/s-0036-1583293
Review Article
Thieme Publicações Ltda Rio de Janeiro, Brazil

Common Dysregulated Genes in Endometriosis and Malignancies

Genes comuns desregulados em endometriose e doenças malignas
Daniel Blasioli Dentillo
1   Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo – USP, Ribeirão Preto, SP, Brasil
,
Juliana Meola
1   Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo – USP, Ribeirão Preto, SP, Brasil
,
Rui Alberto Ferriani
2   Human Reproduction Sector, Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP, Brasil
,
Julio César Rosa-e-Silva
3   Gynecology Surgery Sector, Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP, Brasil
› Author Affiliations
Further Information

Publication History

19 November 2015

07 January 2016

Publication Date:
24 May 2016 (online)

   Permissions and Reprints

Abstract

Several authors have investigated the malignant transformation of endometriosis, which supports the hypothesis of the pre-neoplastic state of endometriotic lesions, but there are few data about the pathways and molecular events related to this phenomenon. This review provides current data about deregulated genes that may function as key factors in the malignant transition of endometriotic lesions. In order to do so, we first searched for studies that have screened differential gene expression between endometriotic tissues and normal endometrial tissue of women without endometriosis, and found only two articles with 139 deregulated genes. Further, using the PubMed database, we crossed the symbol of each gene with the terms related to malignancies, such as cancer and tumor, and obtained 9,619 articles, among which 444 were studies about gene expression associated with specific types of tumor. This revealed that more than 68% of the analyzed genes are also deregulated in cancer. We have also found genes functioning as tumor suppressors and an oncogene. In this study, we present a list of 95 informative genes in order to understand the genetic components that may be responsible for endometriosis' malignant transformation. However, future studies should be conducted to confirm these findings.

Resumo

Vários autores têm estudado transformações malignas em endometriose que suportam a hipótese de um estado pré-neoplásico das lesões endometrióticas; contudo, existem poucos dados sobre as vias e eventos moleculares relacionados a este fenômeno. Esta revisão fornece dados atuais sobre genes desregulados que possam funcionar como fatores-chave para a transição maligna das lesões endometrióticas. Assim, inicialmente, estudos de expressão gênica diferencial em larga escala comparando tecido endometriótico e endométrio normal de mulheres sem endometriose foram procurados, e apenas dois artigos com 139 genes desregulados foram obtidos. Posteriormente, usando o banco de dados do PubMed, foram cruzados os símbolos de cada gene com termos relacionados à malignidade, como câncer e tumor, e 9.619 artigos foram obtidos, dos quais 444 eram estudos sobre expressão de genes associados a tipos específicos de tumor. Isto revela que mais de 68% dos genes analisados eram também desregulados em câncer. Também foram encontrados genes que funcionam como supressor tumoral e um oncogene. Este estudo apresenta uma lista de 95 genes informativos para compreender os componentes genéticos que possam ser responsáveis por transformações malignas na endometriose. Contudo, estudos futuros são necessários para confirmar estes achados.

Keywords

cancer - endometriosis - gene expression

Palavras-chave

câncer - endometriose - expressão gênica
 

  • References

  • 1 Fourquet J, Báez L, Figueroa M, Iriarte RI, Flores I. Quantification of the impact of endometriosis symptoms on health-related quality of life and work productivity. Fertil Steril 2011; 96 (1) 107-112
    CrossrefPubMedGoogle Scholar
  • 2 Meola J, Rosa e Silva JC, Dentillo DB , et al. Differentially expressed genes in eutopic and ectopic endometrium of women with endometriosis. Fertil Steril 2010; 93 (6) 1750-1773
    CrossrefPubMedGoogle Scholar
  • 3 Michaud N, Al-Akoum M, Gagnon G , et al. Decreased concentrations of soluble interleukin-1 receptor accessory protein levels in the peritoneal fluid of women with endometriosis. J Reprod Immunol 2011; 92 (1–2) 68-73
    CrossrefPubMedGoogle Scholar
  • 4 Kokcu A. Relationship between endometriosis and cancer from current perspective. Arch Gynecol Obstet 2011; 284 (6) 1473-1479
    CrossrefPubMedGoogle Scholar
  • 5 Kasvandik S, Samuel K, Peters M , et al. Deep quantitative proteomics reveals extensive metabolic reprogramming and cancer-like changes of ectopic endometriotic stromal cells. J Proteome Res 2016; 15 (2) 572-584
    CrossrefPubMedGoogle Scholar
  • 6 Heaps JM, Nieberg RK, Berek JS. Malignant neoplasms arising in endometriosis. Obstet Gynecol 1990; 75 (6) 1023-1028
    PubMedGoogle Scholar
  • 7 Fishman A, Demirel D, Laucirica R , et al. Malignant tumors arising in endometriosis: clinical-pathological study and flow cytometry analysis. Eur J Obstet Gynecol Reprod Biol 1996; 70 (1) 69-74
    CrossrefPubMedGoogle Scholar
  • 8 Jiang X, Morland SJ, Hitchcock A, Thomas EJ, Campbell IG. Allelotyping of endometriosis with adjacent ovarian carcinoma reveals evidence of a common lineage. Cancer Res 1998; 58 (8) 1707-1712
    PubMedGoogle Scholar
  • 9 Ogawa S, Kaku T, Amada S , et al. Ovarian endometriosis associated with ovarian carcinoma: a clinicopathological and immunohistochemical study. Gynecol Oncol 2000; 77 (2) 298-304
    CrossrefPubMedGoogle Scholar
  • 10 Stern RC, Dash R, Bentley RC, Snyder MJ, Haney AF, Robboy SJ. Malignancy in endometriosis: frequency and comparison of ovarian and extraovarian types. Int J Gynecol Pathol 2001; 20 (2) 133-139
    CrossrefPubMedGoogle Scholar
  • 11 Slomovitz BM, Soslow RA, Chang RC, Golub R, Kuo DY. Serous adenocarcinoma of the inguinal region arising from endometriosis followed by a successful pregnancy. Gynecol Oncol 2002; 87 (1) 152-154
    CrossrefPubMedGoogle Scholar
  • 12 Melin A, Sparén P, Persson I, Bergqvist A. Endometriosis and the risk of cancer with special emphasis on ovarian cancer. Hum Reprod 2006; 21 (5) 1237-1242
    CrossrefPubMedGoogle Scholar
  • 13 Melin A, Sparén P, Bergqvist A. The risk of cancer and the role of parity among women with endometriosis. Hum Reprod 2007; 22 (11) 3021-3026
    CrossrefPubMedGoogle Scholar
  • 14 Efthymiou CA. Endometriosis-associated intestinal tumours: a consequence of long-term unopposed oestrogen?. Ann R Coll Surg Engl 2009; 91 (3) 259-260
    CrossrefPubMedGoogle Scholar
  • 15 Lin PY, Cheng CJ, Lou HY , et al. Deep infiltrating cervical endometriosis mimicking rectosigmoid cancer. Am J Med Sci 2011; 342 (3) 239
    CrossrefPubMedGoogle Scholar
  • 16 Xu B, Hamada S, Kusuki I, Itoh R, Kitawaki J. Possible involvement of loss of heterozygosity in malignant transformation of ovarian endometriosis. Gynecol Oncol 2011; 120 (2) 239-246
    CrossrefPubMedGoogle Scholar
  • 17 Meng Q, Sun W, Jiang J, Fletcher NM, Diamond MP, Saed GM. Identification of common mechanisms between endometriosis and ovarian cancer. J Assist Reprod Genet 2011; 28 (10) 917-923
    CrossrefPubMedGoogle Scholar
  • 18 del Carmen MG. Evidence for the relationship between endometriosis and epithelial ovarian cancer. Obstet Gynecol Surv 2015; 70 (9) 587-595
    CrossrefPubMedGoogle Scholar
  • 19 Seidman JD. Prognostic importance of hyperplasia and atypia in endometriosis. Int J Gynecol Pathol 1996; 15 (1) 1-9
    CrossrefPubMedGoogle Scholar
  • 20 Donnez J, Nisolle M, Gillet N, Smets M, Bassil S, Casanas-Roux F. Large ovarian endometriomas. Hum Reprod 1996; 11 (3) 641-646
    CrossrefPubMedGoogle Scholar
  • 21 Taburiaux L, Pluchino N, Petignat P, Wenger JM. Endometriosis-associated abdominal wall cancer: a poor prognosis?. Int J Gynecol Cancer 2015; 25 (9) 1633-1638
    CrossrefPubMedGoogle Scholar
  • 22 Munksgaard PS, Blaakaer J. The association between endometriosis and gynecological cancers and breast cancer: a review of epidemiological data. Gynecol Oncol 2011; 123 (1) 157-163
    CrossrefPubMedGoogle Scholar
  • 23 Akbarzadeh-Jahromi M, Shekarkhar G, Sari Aslani F, Azarpira N, Heidari Esfahani M, Momtahan M. Prevalence of endometriosis in malignant epithelial ovarian tumor. Arch Iran Med 2015; 18 (12) 844-848
    PubMedGoogle Scholar
  • 24 Yantiss RK, Clement PB, Young RH. Neoplastic and pre-neoplastic changes in gastrointestinal endometriosis: a study of 17 cases. Am J Surg Pathol 2000; 24 (4) 513-524
    CrossrefPubMedGoogle Scholar
  • 25 Szubert M, Suzin J, Stawerski P, Kowalczyk-Amico K, Duechler M. Endometriosis and carcinosarcoma—a hypothetical correlation or a proven pathogenetic pathway? Colon carcinosarcoma with origin in endometriotic foci—a case report. Ginekol Pol 2015; 86 (7) 547-550
    CrossrefPubMedGoogle Scholar
  • 26 Sampson JA. Endometrial carcinoma of the ovary arising in endometrial tissue in that organ. Arch Surg 1925; 10 (1) 1-72
    CrossrefPubMedGoogle Scholar
  • 27 Scott RB. Malignant changes in endometriosis. Obstet Gynecol 1953; 2 (3) 283-289
    PubMedGoogle Scholar
  • 28 Somigliana E, Vigano' P, Parazzini F, Stoppelli S, Giambattista E, Vercellini P. Association between endometriosis and cancer: a comprehensive review and a critical analysis of clinical and epidemiological evidence. Gynecol Oncol 2006; 101 (2) 331-341
    CrossrefPubMedGoogle Scholar
  • 29 Leiserowitz GS, Gumbs JL, Oi R , et al. Endometriosis-related malignancies. Int J Gynecol Cancer 2003; 13 (4) 466-471
    CrossrefPubMedGoogle Scholar
  • 30 Jiang X, Hitchcock A, Bryan EJ , et al. Microsatellite analysis of endometriosis reveals loss of heterozygosity at candidate ovarian tumor suppressor gene loci. Cancer Res 1996; 56 (15) 3534-3539
    PubMedGoogle Scholar
  • 31 Guo SW. Epigenetics of endometriosis. Mol Hum Reprod 2009; 15 (10) 587-607
    CrossrefPubMedGoogle Scholar
  • 32 Lu Y, Cuellar-Partida G, Painter JN , et al; Australian Ovarian Cancer Study; International Endogene Consortium (IEC). Shared genetics underlying epidemiological association between endometriosis and ovarian cancer. Hum Mol Genet 2015; 24 (20) 5955-5964
    CrossrefPubMedGoogle Scholar
  • 33 Gogusev J, Bouquet de Jolinière J, Telvi L , et al. Detection of DNA copy number changes in human endometriosis by comparative genomic hybridization. Hum Genet 1999; 105 (5) 444-451
    CrossrefPubMedGoogle Scholar
  • 34 Gogusev J, Bouquet de Jolinière J, Telvi L , et al. Genetic abnormalities detected by comparative genomic hybridization in a human endometriosis-derived cell line. Mol Hum Reprod 2000; 6 (9) 821-827
    CrossrefPubMedGoogle Scholar
  • 35 Sharpe-Timms KL. Endometrial anomalies in women with endometriosis. Ann N Y Acad Sci 2001; 943: 131-147
    CrossrefPubMedGoogle Scholar
  • 36 Honda H, Barrueto FF, Gogusev J, Im DD, Morin PJ. Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis. Reprod Biol Endocrinol 2008; 6: 59-71
    CrossrefPubMedGoogle Scholar
  • 37 Dentillo DB, Meola J, Rosa e Silva JC , et al. Deregulation of LOXL1 and HTRA1 gene expression in endometriosis. Reprod Sci 2010; 17 (11) 1016-1023
    CrossrefPubMedGoogle Scholar
  • 38 Moss LD, Runals AL. Carcinoma of the ovary arising in an endometrial cyst. N Y State J Med 1948; 48 (4) 401-406
    PubMedGoogle Scholar
  • 39 Hawthorne HR, Kimbrough RA, Davis HC. Concomitant endometriosis and carcinoma of the rectosigmoid. Am J Obstet Gynecol 1951; 62 (3) 681-684
    CrossrefPubMedGoogle Scholar
  • 40 Dockerty MB. Malignancy complicating endometriosis. Pathologic features in 9 cases. Am J Obstet Gynecol 1962; 83 (2) 175-179
    CrossrefPubMedGoogle Scholar
  • 41 Saunders P, Price AB, Taylor RW. Mixed mesodermal tumour of the ovary arising in pelvic endometriosis. Proc R Soc Med 1970; 63 (10) 1050-1051
    PubMedGoogle Scholar
  • 42 Crum CP, Wible J, Frick HC, Fenoglio CM, Richart RM, Williamson S. A case of extensive pelvic endometriosis terminating in endometrial sarcoma. Am J Obstet Gynecol 1981; 140 (6) 718-719
    CrossrefPubMedGoogle Scholar
  • 43 Mckay DC, Ellis JH, Marn CS. CT of mullerian adenosarcoma arising in endometriosis. Clin Imaging 1993; 17 (3) 204-206
    CrossrefPubMedGoogle Scholar
  • 44 Dimoulios P, Koutroubakis IE, Tzardi M, Antoniou P, Matalliotakis IM, Kouroumalis EA. A case of sigmoid endometriosis difficult to differentiate from colon cancer. BMC Gastroenterol 2003; 3: 18-22
    CrossrefPubMedGoogle Scholar
  • 45 Varma R, Rollason T, Gupta JK, Maher ER. Endometriosis and the neoplastic process. Reproduction 2004; 127 (3) 293-304
    CrossrefPubMedGoogle Scholar
  • 46 Sayasneh A, Tsivos D, Crawford R. Endometriosis and ovarian cancer: a systematic review. ISRN Obstet Gynecol 2011; 2011: 140310
    PubMedGoogle Scholar
  • 47 Van Gorp T, Amant F, Neven P, Vergote I, Moerman P. Endometriosis and the development of malignant tumours of the pelvis. A review of literature. Best Pract Res Clin Obstet Gynaecol 2004; 18 (2) 349-371
    CrossrefPubMedGoogle Scholar
  • 48 Burghaus S, Häberle L, Schrauder MG , et al. Endometriosis as a risk factor for ovarian or endometrial cancer - results of a hospital-based case-control study. BMC Cancer 2015; 15: 751-759
    CrossrefPubMedGoogle Scholar
  • 49 Testa AC, Timmerman D, Van Holsbeke C , et al. Ovarian cancer arising in endometrioid cysts: ultrasound findings. Ultrasound Obstet Gynecol 2011; 38 (1) 99-106
    CrossrefPubMedGoogle Scholar
  • 50 Sáinz de la Cuesta R, Izquierdo M, Cañamero M, Granizo JJ, Manzarbeitia F. Increased prevalence of p53 overexpression from typical endometriosis to atypical endometriosis and ovarian cancer associated with endometriosis. Eur J Obstet Gynecol Reprod Biol 2004; 113 (1) 87-93
    CrossrefPubMedGoogle Scholar
  • 51 Yu HC, Lin CY, Chang WC, Shen BJ, Chang WP, Chuang CM ; Task Force on Carcinogenesis of Endometrial Cancer. Increased association between endometriosis and endometrial cancer: a nationwide population-based retrospective cohort study. Int J Gynecol Cancer 2015; 25 (3) 447-452
    CrossrefPubMedGoogle Scholar
  • 52 Brooks JJ, Wheeler JE. Malignancy arising in extragonadal endometriosis: a case report and summary of the world literature. Cancer 1977; 40 (6) 3065-3073
    CrossrefPubMedGoogle Scholar
  • 53 Brinton LA, Gridley G, Persson I, Baron J, Bergqvist A. Cancer risk after a hospital discharge diagnosis of endometriosis. Am J Obstet Gynecol 1997; 176 (3) 572-579
    CrossrefPubMedGoogle Scholar
  • 54 Sainz de la Cuesta R, Eichhorn JH, Rice LW, Fuller Jr AF, Nikrui N, Goff BA. Histologic transformation of benign endometriosis to early epithelial ovarian cancer. Gynecol Oncol 1996; 60 (2) 238-244
    CrossrefPubMedGoogle Scholar
  • 55 Dmowski WP, Radwanska E, Rana N. Recurrent endometriosis following hysterectomy and oophorectomy: the role of residual ovarian fragments. Int J Gynaecol Obstet 1988; 26 (1) 93-103
    CrossrefPubMedGoogle Scholar
  • 56 Judson PL, Temple AM, Fowler Jr WC, Novotny DB, Funkhouser Jr WK. Vaginal adenosarcoma arising from endometriosis. Gynecol Oncol 2000; 76 (1) 123-125
    CrossrefPubMedGoogle Scholar
  • 57 Prowse AH, Manek S, Varma R , et al. Molecular genetic evidence that endometriosis is a precursor of ovarian cancer. Int J Cancer 2006; 119 (3) 556-562
    CrossrefPubMedGoogle Scholar
  • 58 Melin A, Lundholm C, Malki N, Swahn ML, Sparen P, Bergqvist A. Endometriosis as a prognostic factor for cancer survival. Int J Cancer 2011; 129 (4) 948-955
    CrossrefPubMedGoogle Scholar
  • 59 Modesitt SC, Tortolero-Luna G, Robinson JB, Gershenson DM, Wolf JK. Ovarian and extraovarian endometriosis-associated cancer. Obstet Gynecol 2002; 100 (4) 788-795
    CrossrefPubMedGoogle Scholar
  • 60 Keita M, Bessette P, Pelmus M, Ainmelk Y, Aris A. Expression of interleukin-1 (IL-1) ligands system in the most common endometriosis-associated ovarian cancer subtypes. J Ovarian Res 2010; 3: 3
    CrossrefPubMedGoogle Scholar
  • 61 Zanetta GM, Webb MJ, Li H, Keeney GL. Hyperestrogenism: a relevant risk factor for the development of cancer from endometriosis. Gynecol Oncol 2000; 79 (1) 18-22
    CrossrefPubMedGoogle Scholar
  • 62 Munksgaard PS, Blaakaer J. The association between endometriosis and ovarian cancer: a review of histological, genetic and molecular alterations. Gynecol Oncol 2012; 124 (1) 164-169
    CrossrefPubMedGoogle Scholar
  • 63 Eyster KM, Boles AL, Brannian JD, Hansen KA. DNA microarray analysis of gene expression markers of endometriosis. Fertil Steril 2002; 77 (1) 38-42
    CrossrefPubMedGoogle Scholar
  • 64 Hu WP, Tay SK, Zhao Y. Endometriosis-specific genes identified by real-time reverse transcription-polymerase chain reaction expression profiling of endometriosis versus autologous uterine endometrium. J Clin Endocrinol Metab 2006; 91 (1) 228-238
    CrossrefPubMedGoogle Scholar
  • 65 Kyama CM, Overbergh L, Debrock S , et al. Increased peritoneal and endometrial gene expression of biologically relevant cytokines and growth factors during the menstrual phase in women with endometriosis. Fertil Steril 2006; 85 (6) 1667-1675
    CrossrefPubMedGoogle Scholar
  • 66 Arimoto T, Katagiri T, Oda K , et al. Genome-wide cDNA microarray analysis of gene-expression profiles involved in ovarian endometriosis. Int J Oncol 2003; 22 (3) 551-560
    PubMedGoogle Scholar
  • 67 Barbolina MV, Adley BP, Kelly DL , et al. Downregulation of connective tissue growth factor by three-dimensional matrix enhances ovarian carcinoma cell invasion. Int J Cancer 2009; 125 (4) 816-825
    CrossrefPubMedGoogle Scholar
  • 68 Braig S, Wallner S, Junglas B, Fuchshofer R, Bosserhoff AK. CTGF is overexpressed in malignant melanoma and promotes cell invasion and migration. Br J Cancer 2011; 105 (2) 231-238
    CrossrefPubMedGoogle Scholar
  • 69 Todorović-Raković N, Nešković-Konstantinović Z, Nikolić-Vukosavljević D. C-myc as a predictive marker for chemotherapy in metastatic breast cancer. Clin Exp Med 2012; 12 (4) 217-223
    CrossrefPubMedGoogle Scholar
  • 70 Yang Z, Zhou X, Liu Y , et al. Activation of integrin β1 mediates the increased malignant potential of ovarian cancer cells exerted by inflammatory cytokines. Anticancer Agents Med Chem 2014; 14 (7) 955-962
    CrossrefPubMedGoogle Scholar
  • 71 Wang XM, Li J, Yan MX , et al. Integrative analyses identify osteopontin, LAMB3 and ITGB1 as critical pro-metastatic genes for lung cancer. PLoS ONE 2013; 8 (2) e55714
    CrossrefPubMedGoogle Scholar
  • 72 Erdem M, Erdem S, Sanli O , et al. Up-regulation of TGM2 with ITGB1 and SDC4 is important in the development and metastasis of renal cell carcinoma. Urol Oncol 2014; 32 (1) 25.e13-25.e20
    CrossrefPubMedGoogle Scholar
  • 73 Clark EA, Golub TR, Lander ES, Hynes RO. Genomic analysis of metastasis reveals an essential role for RhoC. Nature 2000; 406 (6795) 532-535
    CrossrefPubMedGoogle Scholar
  • 74 Keller ET. Metastasis suppressor genes: a role for raf kinase inhibitor protein (RKIP). Anticancer Drugs 2004; 15 (7) 663-669
    CrossrefPubMedGoogle Scholar
  • 75 Cao XX, Xu JD, Xu JW , et al. RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo. Breast Cancer Res Treat 2010; 123 (2) 375-386
    CrossrefPubMedGoogle Scholar
  • 76 Gibert B, Hadchity E, Czekalla A , et al. Inhibition of heat shock protein 27 (HspB1) tumorigenic functions by peptide aptamers. Oncogene 2011; 30 (34) 3672-3681
    CrossrefPubMedGoogle Scholar
  • 77 Desprez PY, Lin CQ, Thomasset N, Sympson CJ, Bissell MJ, Campisi J. A novel pathway for mammary epithelial cell invasion induced by the helix-loop-helix protein Id-1. Mol Cell Biol 1998; 18 (8) 4577-4588
    CrossrefPubMedGoogle Scholar
  • 78 Lin CQ, Singh J, Murata K , et al. A role for Id-1 in the aggressive phenotype and steroid hormone response of human breast cancer cells. Cancer Res 2000; 60 (5) 1332-1340
    PubMedGoogle Scholar
  • 79 Takai N, Miyazaki T, Fujisawa K, Nasu K, Miyakawa I. Id1 expression is associated with histological grade and invasive behavior in endometrial carcinoma. Cancer Lett 2001; 165 (2) 185-193
    CrossrefPubMedGoogle Scholar
  • 80 Schindl M, Oberhuber G, Obermair A, Schoppmann SF, Karner B, Birner P. Overexpression of Id-1 protein is a marker for unfavorable prognosis in early-stage cervical cancer. Cancer Res 2001; 61 (15) 5703-5706
    PubMedGoogle Scholar
  • 81 Cabodi S, del Pilar Camacho-Leal M, Di Stefano P, Defilippi P. Integrin signalling adaptors: not only figurants in the cancer story. Nat Rev Cancer 2010; 10 (12) 858-870
    CrossrefPubMedGoogle Scholar
  • 82 Swiersz LM. Role of endometriosis in cancer and tumor development. Ann N Y Acad Sci 2002; 955: 281-292 , discussion 293–295, 396–406
    CrossrefPubMedGoogle Scholar
  • 83 Viganó P, Somigliana E, Chiodo I, Abbiati A, Vercellini P. Molecular mechanisms and biological plausibility underlying the malignant transformation of endometriosis: a critical analysis. Hum Reprod Update 2006; 12 (1) 77-89
    PubMedGoogle Scholar
  • 84 Shackleton M, Quintana E, Fearon ER, Morrison SJ. Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell 2009; 138 (5) 822-829
    CrossrefPubMedGoogle Scholar
  • 85 Cao Y, DePinho RA, Ernst M, Vousden K. Cancer research: past, present and future. Nat Rev Cancer 2011; 11 (10) 749-754
    CrossrefPubMedGoogle Scholar
  • 86 Prowse AH, Fakis G, Manek S , et al. Allelic loss studies do not provide evidence for the “endometriosis-as-tumor” theory. Fertil Steril 2005; 83 (Suppl. 01) 1134-1143
    CrossrefPubMedGoogle Scholar