{"paper_id":"d47ce820-9982-4cf0-b237-31bcd5924384","body_text":"Abstract\nBackground\nTo examine the effects of adenomyosis on tumor progression and survival outcome of endometrial cancer patients.\nMethods\nThis is a retrospective study examining stage I–IV endometrial cancer patients who underwent hysterectomy-based surgical staging (n = 571), and endometrial hyperplasia patients who underwent hysterectomy (n = 213). Clinical demographics, histopathological factors, and survival outcomes were analyzed based on the presence or absence of adenomyosis.\nResults\nAmong the endometrial cancer cohort, adenomyosis was observed in 47.5 % of cases and was significantly associated with lower grade (grade 1–2 tumors, 81.2 vs. 73.3 %; p = 0.028), earlier stage (stage I disease, 74.8 vs. 64.3 %; p = 0.023), and lower likelihood of deep myometrial invasion (19.2 vs. 28.2 %; p = 0.039) and cervical invasion (13.7 vs. 21.2 %; p = 0.024) than those without adenomyosis. In survival analysis, endometrial cancer coexisting with adenomyosis was associated with a significantly better disease-free survival (5-year rate, 89.2 vs. 78.2 %; p < 0.001) and overall survival (91.8 vs. 83.9 %; p = 0.004) after hysterectomy. In multivariate analysis, controlling for other significant variables in univariate analysis, presence of adenomyosis remained an independent prognostic factor associated with decreased risk of disease recurrence after surgery (hazard ratio [HR] 0.53; 95 % confidence interval [CI] 0.30–0.92; p = 0.023). Endometrial hyperplasia had a significantly increased incidence of adenomyosis when compared with type I endometrial cancer (grade 1–2 endometrioid adenocarcinoma, n = 411) on multivariate analysis (62.9 vs. 48.9 %; HR 1.88; 95 % CI 1.32–2.69; p < 0.001).\nConclusions\nAdenomyosis appears to be associated with less aggressive tumor behavior of endometrial cancer, suggesting that it may have inhibitory effects on the progression of this disease.\nSimilar content being viewed by others\nReferences\nSiegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11-30.\nWright JD, Barrena Medel NI, Sehouli J, Fujiwara K, Herzog TJ. Contemporary management of endometrial cancer. Lancet. 2012;379:1352–60.\nGarcia L, Isaacson K. Adenomyosis: review of the literature. J Minim Invasive Gynecol. 2011;18:428–37.\nKairi-Vassilatou E, Kontogianni K, Salamalekis M, Sykiotis K, Kondi-Pafitis A. A clinicopathological study of the relationship between adenomyosis and other hormone-dependent uterine lesions. Eur J Gynaecol Oncol. 2004;25:222–4.\nWinkelman J, Robinson R. Adenocarcinoma of endometrium involving adenomyosis. Report of an unusual case and review of the literature. Cancer. 1966;19:901–8.\nHernandez E, Woodruff JD. Endometrial adenocarcinoma arising in adenomyosis. Am J Obstet Gynecol. 1980;138:827–32.\nWoodruff JD, Erozan YS, Genadry R. Adenocarcinoma arising in adenomyosis detected by atypical cytology. Obstet Gynecol. 1986;67:145–8.\nKuwashima Y, Uehara T, Kishi K, et al. Intramural adenocarcinoma of the uterus, arisen from adenomyosis uteri, showing unique histologic appearances. Report of two cases. Eur J Gynaecol Oncol. 1994;15:418–23.\nHayata T, Tanaka Y, Miyakawa I. Endometrial cancer associated with adenomyosis. Int J Gynaecol Obstet. 1994;44:76–7.\nTakai N, Akizuki S, Nasu K, Etoh Y, Miyakawa I. Endometrioid adenocarcinoma arising from adenomyosis. Gynecol Obstet Invest. 1999;48:141–4.\nSasaki T, Sugiyama T, Nanjo H, et al. Endometrioid adenocarcinoma arising from adenomyosis: report and immunohistochemical analysis of an unusual case. Pathol Int. 2001;51:308–13.\nIchikawa Y, Takano K, Higa S, et al. Endometrial carcinoma coexisting with pregnancy, presumed to derive from adenomyosis: a case report. Int J Gynecol Cancer. 2001;11:488–90.\nKoshiyama M, Suzuki A, Ozawa M, et al. Adenocarcinomas arising from uterine adenomyosis: a report of four cases. Int J Gynecol Pathol. 2002;21:239–45.\nCouto D, Mota F, Silva T, de Oliveira C. Adenocarcinoma arising in adenomyosis: report of an unusual case. Acta Obstet Gynecol Scand. 2004;83:406–8.\nTakeuchi K, Yamanaka Y, Hamana S, Ohara N, Maruo T. Invasive adenocarcinoma arising from uterine adenomyosis involving the rectosigmoid colon. Int J Gynecol Cancer. 2004;14:1004–6.\nHsu MI, Chou SY, Lin SE, Liang SJ, Chiu HC, Hsu CS. Very early stage adenocarcinoma arising from adenomyosis in the uterus. Taiwan J Obstet Gynecol. 2006;45:346–9.\nIzadi-Mood N, Samadi N, Sarmadi S, Eftekhar Z. Papillary serous carcinoma arising from adenomyosis presenting as intramural leiomyoma. Arch Iran Med. 2007;10:258–60.\nIsmiil ND, Rasty G, Ghorab Z, et al. Adenomyosis is associated with myometrial invasion by FIGO 1 endometrial adenocarcinoma. Int J Gynecol Pathol. 2007;26:278–83.\nPuppa G, Shozu M, Perin T, et al. Small primary adenocarcinoma in adenomyosis with nodal metastasis: a case report. BMC Cancer. 2007;7:103.\nIsmiil N, Rasty G, Ghorab Z, et al. Adenomyosis involved by endometrial adenocarcinoma is a significant risk factor for deep myometrial invasion. Ann Diagn Pathol. 2007;11:252–7.\nOhta Y, Hamatani S, Suzuki T, et al. Clear cell adenocarcinoma arising from a giant cystic adenomyosis: a case report with immunohistochemical analysis of laminin-5 gamma2 chain and p53 overexpression. Pathol Res Pract. 2008;204:677–82.\nMotohara K, Tashiro H, Ohtake H, Saito F, Ohba T, Katabuchi H. Endometrioid adenocarcinoma arising in adenomyosis: elucidation by periodic magnetic resonance imaging evaluations. Int J Clin Oncol. 2008;13:266–70.\nHirabayashi K, Yasuda M, Kajiwara H, et al. Clear cell adenocarcinoma arising from adenomyosis. Int J Gynecol Pathol. 2009;28:262–6.\nKazandi M, Zeybek B, Terek MC, Zekioglu O, Ozdemir N, Oztekin K. Grade 2 endometrioid adenocarcinoma arising from adenomyosis of the uterus: report of a case. Eur J Gynaecol Oncol. 2010;31:719–21.\nAbushahin N, Zhang T, Chiang S, Zhang X, Hatch K, Zheng W. Serous endometrial intraepithelial carcinoma arising in adenomyosis: a report of 5 cases. Int J Gynecol Pathol. 2011;30:271–81.\nKucera E, Hejda V, Dankovcik R, Valha P, Dudas M, Feyereisl J. Malignant changes in adenomyosis in patients with endometrioid adenocarcinoma. Eur J Gynaecol Oncol. 2011;32:182–4.\nBoes AS, Tousseyn T, Vandenput I, et al. Pitfall in the diagnosis of endometrial cancer: case report of an endometrioid adenocarcinoma arising from uterine adenomyosis. Eur J Gynaecol Oncol. 2011;32:431–4.\nQuick CM, May T, Horowitz NS, Nucci MR. Low-grade, low-stage endometrioid endometrial adenocarcinoma: a clinicopathologic analysis of 324 cases focusing on frequency and pattern of myoinvasion. Int J Gynecol Pathol. 2012;31:337–43.\nHanley KZ, Dustin SM, Stoler MH, Atkins KA. The significance of tumor involved adenomyosis in otherwise low-stage endometrioid adenocarcinoma. Int J Gynecol Pathol. 2010;29:445–51.\nHall JB, Young RH, Nelson JH Jr. The prognostic significance of adenomyosis in endometrial carcinoma. Gynecol Oncol. 1984;17:32–40.\nJacques SM, Lawrence WD. Endometrial adenocarcinoma with variable-level myometrial involvement limited to adenomyosis: a clinicopathologic study of 23 cases. Gynecol Oncol. 1990;37:401–7.\nMittal KR, Barwick KW. Endometrial adenocarcinoma involving adenomyosis without true myometrial invasion is characterized by frequent preceding estrogen therapy, low histologic grades, and excellent prognosis. Gynecol Oncol. 1993;49:197–201.\nKoshiyama M, Okamoto T, Ueta M. The relationship between endometrial carcinoma and coexistent adenomyosis uteri, endometriosis externa and myoma uteri. Cancer Detect Prev. 2004;28:94–8.\nMusa F, Frey MK, Im HB, Chekmareva M, Ellenson LH, Holcomb K. Does the presence of adenomyosis and lymphovascular space invasion affect lymph node status in patients with endometrioid adenocarcinoma of the endometrium? Am J Obstet Gynecol. 2012;207:417.e1-6.\nGun I, Oner O, Bodur S, Ozdamar O, Atay V. Is adenomyosis associated with the risk of endometrial cancer? Med Glas (Zenica). 2012;9:268–72.\nSotnikova N, Antsiferova I, Malyshkina A. Cytokine network of eutopic and ectopic endometrium in women with adenomyosis. Am J Reprod Immunol. 2002;47:251–5.\nWang F, Li H, Yang Z, Du X, Cui M, Wen Z. Expression of interleukin-10 in patients with adenomyosis. Fertil Steril. 2009;91:1681–5.\nIkeda H, Old LJ, Schreiber RD. The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev. 2002;13:95–109.\nFerrantini M, Capone I, Belardelli F. Interferon-alpha and cancer: mechanisms of action and new perspectives of clinical use. Biochimie. 2007;89:884–93.\nvan Horssen R, Ten Hagen TL, Eggermont AM. TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility. Oncologist. 2006;11:397–408.\nTagashira Y, Taniguchi F, Harada T, Ikeda A, Watanabe A, Terakawa N. Interleukin-10 attenuates TNF-alpha-induced interleukin-6 production in endometriotic stromal cells. Fertil Steril. 2009;91:2185–92.\nZitvogel L, Kepp O, Galluzzi L, Kroemer G. Inflammasomes in carcinogenesis and anticancer immune responses. Nat Immunol. 2012;13:343–51.\nPalena C, Hamilton DH, Fernando RI. Influence of IL-8 on the epithelial-mesenchymal transition and the tumor microenvironment. Future Oncol. 2012;8:713–22.\nYang JH, Wu MY, Chen CD, Chen MJ, Yang YS, Ho HN. Altered apoptosis and proliferation in endometrial stromal cells of women with adenomyosis. Hum Reprod. 2007;22:945–52.\nMehasseb MK, Bell SC, Brown L, Pringle JH, Habiba M. Phenotypic characterisation of the inner and outer myometrium in normal and adenomyotic uteri. Gynecol Obstet Invest. 2011;71:217–24.\nBenagiano G, Habiba M, Brosens I. The pathophysiology of uterine adenomyosis: an update. Fertil Steril. 2012;98:572–9.\nVercellini P, Vigano P, Somigliana E, Daguati R, Abbiati A, Fedele L. Adenomyosis: epidemiological factors. Best Pract Res Clin Obstet Gynaecol. 2006;20:465–77.\nKoike N, Tsunemi T, Uekuri C, et al. Pathogenesis and malignant transformation of adenomyosis (review). Oncol Rep. 2013;29:861–7.\nAcknowledgment\nNo funding support was provided for this study.\nDisclosure\nKoji Matsuo, Sigita S. Cahoon, Marc Gualtieri, Christopher A. Scannell, Carrie E. Jung, Tadao Takano, Richard J. Paulson, Laila I. Muderspach, and Lynda D. Roman declare that there are no conflicts of interest for this study.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nRights and permissions\nAbout this article\nCite this article\nMatsuo, K., Cahoon, S.S., Gualtieri, M. et al. Significance of Adenomyosis on Tumor Progression and Survival Outcome of Endometrial Cancer. Ann Surg Oncol 21, 4246–4255 (2014). https://doi.org/10.1245/s10434-014-3880-6\nReceived:\nPublished:\nIssue date:\nDOI: https://doi.org/10.1245/s10434-014-3880-6","source_license":"CC0","license_restricted":false}