Squamous differentiation portends poor prognosis in low and intermediate-risk endometrioid endometrial cancer

English version

Autoři: Diocesio Alves Pinto de Andrade ^aff001; Vinicius Duval da Silva ^aff003; Graziela de Macedo Matsushita ^aff003; Marcos Alves de Lima ^aff004; Marcelo de Andrade Vieira ^aff005; Carlos Eduardo Mattos Cunha Andrade ^aff005; Ronaldo Luís Schmidt ^aff005; Rui Manuel Reis ^aff002; Ricardo dos Reis ^aff005
Působiště autorů: Departament of Oncology, InORP ONCOCLÍNICAS Group (Oncology Institute of Ribeirão Preto), Ribeirão Preto, São Paulo, Brazil ^aff001; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil ^aff002; Departament of Pathology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil ^aff003; Epidemiology and Biostatistics Nucleus, Barretos Cancer Hospital, Barretos, São Paulo, Brazil ^aff004; Department of Gynecologic Oncology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil ^aff005; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal ^aff006; ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal ^aff007
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0220086

Souhrn

Background

Endometrial cancer presents well-defined risk factors: myometrial invasion, histological subtype, tumor grade, lymphovascular space invasion (LVSI). Some low and intermediate-risk endometrioid endometrial cancer patients exhibited unexpected outcomes. This study aimed to investigate other clinical-pathological factors that might influence the recurrence rates of patients diagnosed with low and intermediate-risk endometrioid endometrial cancer.

Methods

A case-control study from a cohort retrospective of 196 patients diagnosed with low and intermediate-risk endometrioid endometrial cancer at a single institution from 2009 to 2014 was conducted. Medical records were reviewed to compare clinical (race, smoking, menopause age, body mass index) and pathological (endometrioid vs endometrioid with squamous differentiation, tumor differentiation grade, tumor location, endocervical invasion, LVSI) features of patients with recurrence (case) and without recurrence (control) of disease. Three controls for each case were matched for age and staging.

Results

Twenty-one patients with recurrence were found (10.7%), of which 14 were stage IA, and 7 were stage IB. In accordance, 63 patients without recurrence were selected as controls. There were no significant differences in any clinical characteristics between cases and controls. Among pathological variables, presence of squamous differentiation (28.6% vs. 4.8%, p = 0.007), tumor differentiation grade 2 or 3 (57.1% vs. 30.2%, p = 0.037) and presence of endocervical invasion (28.6% vs. 12.7%, p = 0.103) were associated with disease recurrence on a univariate analysis. On multivariable analysis, only squamous differentiation was a significant risk factor for recurrence (p = 0.031).

Conclusion

Our data suggest that squamous differentiation may be an adverse prognostic factor in patients with low and intermediate-risk endometrioid endometrial cancer, that showed a 5.6-fold increased risk for recurrence.

Klíčová slova:

Cancer detection and diagnosis – Surgical and invasive medical procedures – Surgical oncology – Prognosis – Histology – Differentiated tumors – Uterine cancer

Zdroje

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. 2018;68(1):7–30.

2. Estimativa 2018: Incidência de Câncer no Brasil. [Internet] Rio de Janeiro: INCA–Instituto Nacional de Câncer José Alencar Gomes da Silva; 2018 [cited 10 Ago 2018];www.inca.gov.br/estimativa/2018/.

3. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983;15(1):10–7. doi: 10.1016/0090-8258(83)90111-7 6822361

4. Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC Astec trial): a randomised study. Lancet 2009;373(9658):125–36. doi: 10.1016/S0140-6736(08)61766-3 19070889

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

6. Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. 1987;60(8 Suppl):2035–41. doi: 10.1002/1097-0142(19901015)60:8+<2035::aid-cncr2820601515>3.0.co;2-8 3652025

7. dos Reis R, Burzawa JK, Tsunoda AT, Hosaka M, Frumovitz M, Westin SN, et al. Lymphovascular Space Invasion Portends Poor Prognosis in Low-Risk Endometrial Cancer. Int J Gynecol Cancer. 2015;25(7):1292–9. doi: 10.1097/IGC.0000000000000490 26067863

8. AlHilli MM, Mariani A, Bakkum-Gamez JN, Dowdy SC, Weaver AL, Peethambaram PP, et al. Risk-scoring models for individualized prediction of overall survival in low-grade and high-grade endometrial cancer. Gynecol Oncol. 2014;133(3):485–93. doi: 10.1016/j.ygyno.2014.03.567 24690476

9. Zeimet AG, Reimer D, Huszar M, Winterhoff B, Puistola U, Azim SA, et al. L1CAM in early-stage type I endometrial cancer: results of a large multicenter evaluation. J Natl Cancer Inst. 2013;105(15):1142–50. doi: 10.1093/jnci/djt144 23781004

10. Zaino RJ, Kurman RJ. Squamous differentiation in carcinoma of the endometrium: a critical appraisal of adenoacanthoma and adenosquamous carcinoma. Semin Diagn Pathol. 1988;5(2):154–71. 3041509

11. Kurman RJ, Carcangiu ML, Herrington CS, Young RH. Tumours of the uterine corpus. WHO Classification of Tumours of Female Reproductive Organs. 4th Edition ed. Lyon: International Agency for Research on Cancer (IARC); 2014. p. 121–54.

12. Abeler VM, Kjorstad KE. Endometrial adenocarcinoma with squamous cell differentiation. Cancer. 1992;69(2):488–95. doi: 10.1002/1097-0142(19920115)69:2<488::aid-cncr2820690236>3.0.co;2-o 1728379

13. Misirlioglu S, Guzel AB, Gulec UK, Gumurdulu D, Vardar MA. Prognostic factors determining recurrence in early-stage endometrial cancer. Eur J Gynaecol Oncol. 2012;33(6):610–4. 23327055

14. Zaino RJ, Kurman R, Herbold D, Gliedman J, Bundy BN, Voet R, et al. The significance of squamous differentiation in endometrial carcinoma. Data from a Gynecologic Oncology Group study. Cancer. 1991;68(10):2293–302. doi: 10.1002/1097-0142(19911115)68:10<2293::aid-cncr2820681032>3.0.co;2-v 1913465

15. Ellenson LH, Ronnett BM, Soslow RA, Zaino RJ, Kurman RJ. Endometrial Carcinoma. In: Kurman RJ, Ellenson LH, Ronnett BM, editors. Blaustein’s Pathology of the Female Genital Tract. Sixth Edition ed. New York: Springer; 2011. p. 393–452.

16. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81. doi: 10.1016/j.jbi.2008.08.010 18929686

17. Stefansson IM, Salvesen HB, Akslen LA. Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients. Int J Cancer. 2006;118(5):1227–33. doi: 10.1002/ijc.21415 16152605

18. Blanco LZ Jr., Heagley DE, Lee JC, Gown AM, Gattuso P, Rotmensch J, et al. Immunohistochemical characterization of squamous differentiation and morular metaplasia in uterine endometrioid adenocarcinoma. Int J Gynecol Pathol. 2013;32(3):283–92. doi: 10.1097/PGP.0b013e31826129e1 23518912

19. Zaino RJ. FIGO staging of endometrial adenocarcinoma: a critical review and proposal. Int J Gynecol Pathol. 2009;28(1):1–9. doi: 10.1097/PGP.0b013e3181846c6d 19047915

20. Hayes MP, Wang H, Espinal-Witter R, Douglas W, Solomon GJ, Baker SJ, et al. PIK3CA and PTEN mutations in uterine endometrioid carcinoma and complex atypical hyperplasia. Clin Cancer Res. 2006;12(20 Pt 1):5932–5. doi: 10.1158/1078-0432.CCR-06-1375 17062663

21. Jiang W, Chen J, Tao X, Huang F, Zhu M, Wang C, et al. Possible Risk Factors of Pulmonary Metastases in Patients With International Federation of Gynecology and Obstetrics Stage I Endometrioid-Type Endometrial Cancer. Int J Gynecol Cancer. 2017;27(6):1206–15. doi: 10.1097/IGC.0000000000001002 28448305

22. Sturgeon SR, Sherman ME, Kurman RJ, Berman ML, Mortel R, Twiggs LB, et al. Analysis of histopathological features of endometrioid uterine carcinomas and epidemiologic risk factors. Cancer Epidemiol Biomarkers Prev. 1998;7(3):231–5. 9521439

23. Lax SF, Pizer ES, Ronnett BM, Kurman RJ. Comparison of estrogen and progesterone receptor, Ki-67, and p53 immunoreactivity in uterine endometrioid carcinoma and endometrioid carcinoma with squamous, mucinous, secretory, and ciliated cell differentiation. Hum Pathol. 1998;29(9):924–31. doi: 10.1016/s0046-8177(98)90197-6 9744308

24. Silberg DG, Swain GP, Suh ER, Traber PG. Cdx1 and cdx2 expression during intestinal development. Gastroenterology. 2000;119(4):961–71. doi: 10.1053/gast.2000.18142 11040183

25. Wani Y, Notohara K, Saegusa M, Tsukayama C. Aberrant Cdx2 expression in endometrial lesions with squamous differentiation: important role of Cdx2 in squamous morula formation. Hum Pathol. 2008;39(7):1072–9. doi: 10.1016/j.humpath.2007.07.019 18495206

26. Caponio MA, Addati T, Popescu O, Petroni S, Rubini V, Centrone M, et al. P16(INK4a) protein expression in endocervical, endometrial and metastatic adenocarcinomas of extra-uterine origin: diagnostic and clinical considerations. Cancer Biomark. 2014;14(2–3):169–75. doi: 10.3233/CBM-130326 24878818

27. Chew I, Post MD, Carinelli SG, Campbell S, Di Y, Soslow RA, et al. p16 expression in squamous and trophoblastic lesions of the upper female genital tract. Int J Gynecol Pathol. 2010;29(6):513–22. doi: 10.1097/PGP.0b013e3181e2fe70 20881863

28. Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, et al. Carcinoma of the corpus uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006;95 Suppl 1:S105–43.