High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients
Yıl: 2023 Cilt: 39 Sayı: 1 Sayfa Aralığı: 75 - 82 Metin Dili: İngilizce DOI: 10.5146/tjpath.2022.01596 İndeks Tarihi: 15-05-2023
High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients
Öz: Objective: The mortality incidence of endometrial carcinomas (ECs) has increased in recent years. Therefore, recent studies have focused on the cellular and microenvironmental properties of ECs. Tumor-infiltrating lymphocytes (TILs), a component of the microenvironment, have been found to be associated with the prognosis in many tumors. Although TILs were mostly evaluated by immunohistochemical studies in ECs, in our study, the evaluation was done with a light microscope as a practical approach, and we aimed to determine the prognostic importance of TILs in endometrioid ECs. Material and Method: 104 patients were included in the study. TILs in the stromal area (sTILs) were evaluated on hematoxylin and eosin (HE) stained-sections at X200 objective. The presence of TILs was evaluated as follows; 0-10% as low, 20-40% as moderate, and 50-90% as intense. Then TILs were grouped as low and high. Results: Tumors with high TILs were more prone to have FIGO (International Federation of Gynecology and Obstetrics) grade 1 tumors, low nuclear grade, early pathological stage, smaller size, no lymphovascular invasion, myometrial invasion below 50%, and no cervical involvement. In the presence of high TILs, the overall survival showed significant increase but no significant correlation was found with disease-free survival. Conclusion: Interest in the molecular properties of ECs has increased in recent years. TIL, which can be easily evaluated in HE sections, is an important parameter in patient selection for molecular tests and determining the prognosis of patients.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Travaglino A, Raffone A, Stradella C, Esposito R, Moretta P, Gallo C, Orlandi G, Insabato L, Zullo F. Impact of endometrial carcinoma histotype on the prognostic value of the TCGA molecular subgroups. Arch Gynecol Obstet. 2020;301:1355-63.
- 2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5-29.
- 3. Gilks CB, Oliva E, Soslow RA. Poor interobserver reproducibility in the diagnosis of high-grade endometrial carcinoma. Am J Surg Pathol. 2013;37:874-81.
- 4. Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497:67- 73.
- 5. Travaglino A, Raffone A, Mollo A, Borrelli G, Alfano P, Zannoni GF, Insabato L, Zullo F. TCGA molecular subgroups and FIGO grade in endometrial endometrioid carcinoma. Arch Gynecol Obstet. 2020;301:1117-25.
- 6. Raffone A, Travaglino A, Raimondo D, Boccellino MP, Maletta M, Borghese G, Casadio P, Insabato L, Mollo A, Zullo F, Seracchioli R.. Tumor-infiltrating lymphocytes and POLE mutation in endometrial carcinoma. Gynecol Oncol. 2021;161:621-8.
- 7. Talhouk A, Derocher H, Schmidt P, Leung S, Milne K, Gilks CB, Anglesio MS, Nelson BH, McAlpine JN. Molecular subtype not immune response drives outcomes in endometrial carcinoma. Clin Cancer Res. 2019;25:2537-48.
- 8. Raffone A, Travaglino A, D’Antonio A, De Marco M, Caccese M, Mascolo M, Insabato L, Zeppa P, Rosati A, Mollo A, Zullo F, Guida M. BAG3 expression correlates with the grade of dysplasia in squamous intraepithelial lesions of the uterine cervix. Acta Obstet Gynecol Scand. 2020;99:99-104.
- 9. Travaglino A, Raffone A, Saccone G, Mascolo M, D’Alessandro P, Arduino B, Mollo A, Insabato L, Zullo F. Nuclear expression of β-catenin in endometrial hyperplasia as marker of premalignancy. APMIS. 2019;127:699-709.
- 10. Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault- Llorca F, Perez EA, Thompson EA, Symmans WF, Richardson AL, Brock J, Criscitiello C, Bailey H, Ignatiadis M, Floris G, Sparano J, Kos Z, Nielsen T, Rimm DL, Allison KH, Reis-Filho JS, Loibl S, Sotiriou C, Viale G, Badve S, Adams S, Willard-Gallo K, Loi S. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: Recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26:259-71.
- 11. Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden GGGM, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, Srinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P, Klauschen F, Watson PH, Nelson BH, Criscitiello C, O’Toole S, Larsimont D, de Wind R, Curigliano G, André F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB. Assessing tumor-infiltrating lymphocytes in solid tumors: A practical review for pathologists and proposal for a standardized method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in melanoma, gastrointestinal tract carcinomas, non-small cell lung carcinoma and mesothelioma, endometrial and ovarian carcinomas, squamous cell carcinoma of the head and neck, genitourinary carcinomas, and primary brain tumors. Adv Anat Pathol. 2017;24:311-35.
- 12. Matias-Guiu X, Oliva E, McCluggage WG. Tumours of the uterine corpus. In: WHO Classification of Tumours Editorial Board. Female genital tumours. Lyon: International Agency for Research on Cancer, 5th edition, 2020, Volume 4.
- 13. Amant F, Mirza MR, Koskas M, Creutzberg CL. Cancer of the corpus uteri. Int J Gynaecol Obstet. 2018;143:37-50.
- 14. Sauerbrei W, Taube SE, McShane LM, Cavenagh MM, Altman DG. Reporting Recommendations for TumorMarker Prognostic Studies (REMARK): An abridged explanation and elaboration. J Natl Cancer Inst. 2018;110:803-11.
- 15. Soo RA, Chen Z, Yan Teng RS, Tan HL, Iacopetta B, Tai BC, Soong R. Prognostic significance of immune cells in non-small cell lung cancer: Meta-analysis. Oncotarget. 2018;9(37):24801- 20.
- 16. Guo F, Dong Y, Tan Q, Kong J, Yu B. Tissue infiltrating immune cells as prognostic biomarkers in endometrial cancer: A meta- analysis. Dis Markers. 2020;2020:1805764.
- 17. Salvesen HB, MacDonald N, Ryan A, Iversen OE, Jacobs IJ, Akslen LA, Das S. Methylation of hMLH1 in a population-based series of endometrial carcinomas. Clin Cancer Res. 2000;6:3607- 13.
- 18. Hampel H, Frankel W, Panescu J, Lockman J, Sotamaa K, Fix D, Comeras I, La Jeunesse J, Nakagawa H, Westman JA, Prior TW, Clendenning M, Penzone P, Lombardi J, Dunn P, Cohn DE, Copeland L, Eaton L, Fowler J, Lewandowski G, Vaccarello L, Bell J, Reid G, de la Chapelle A. Screening for lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res. 2006;66:7810-7.
- 19. Mills AM, Longacre TA. Lynch syndrome screening in the gynecologic tract: Current state of the art. Am J Surg Pathol. 2016;40:e35-e44.
- 20. Shia J, Black D, Hummer AJ, Boyd J, Soslow RA. Routinely assessed morphological features correlate with microsatellite instability status in endometrial cancer. Hum Pathol. 2008;39:116-25.
- 21. Church DN, Briggs SE, Palles C, Domingo E, Kearsey SJ, Grimes JM, Gorman M, Martin L, Howarth KM, Hodgson SV; NSECG Collaborators, Kaur K, Taylor J, Tomlinson IP. DNA polymerase ε and δ exonuclease domain mutations in endometrial cancer. Hum Mol Genet. 2013;22:2820-8.
- 22. Van Gool IC, Ubachs JEH, Stelloo E, de Kroon CD, Goeman JJ, Smit VTHBM, Creutzberg CL, Bosse T. Blinded histopathological characterisation of POLE exonuclease domain-mutant endometrial cancers: Sheep in wolf’s clothing. Histopathology. 2018;72:248-58.
- 23. Howitt BE, Shukla SA, Sholl LM, Ritterhouse LL, Watkins JC, Rodig S, Stover E, Strickland KC, D’Andrea AD, Wu CJ, Matulonis UA, Konstantinopoulos PA. Association of polymerase e-mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1 and PD-L1. JAMA Oncol. 2015;1:1319-23.
- 24. Hussein YR, Weigelt B, Levine DA, Schoolmeester JK, Dao LN, Balzer BL, Liles G, Karlan B, Köbel M, Lee CH, Soslow RA. Clinicopathological analysis of endometrial carcinomas harboring somatic POLE exonuclease domain mutations. Mod Pathol. 2015;28:505-14.
- 25. van Gool IC, Eggink FA, Freeman-Mills L, Stelloo E, Marchi E, de Bruyn M, Palles C, Nout RA, de Kroon CD, Osse EM, Klenerman P, Creutzberg CL, Tomlinson IP, Smit VT, Nijman HW, Bosse T, Church DN. POLE proofreading mutations elicit an antitumor immune response in endometrial cancer. Clin Cancer Res. 2015;21:3347-55.
- 26. de Jong RA, Leffers N, Boezen HM, ten Hoor KA, van der Zee AG, Hollema H, Nijman HW. Presence of tumor-infiltrating lymphocytes is an independent prognostic factor in type I and II endometrial cancer. Gynecol Oncol. 2009;114:105-10.
- 27. Giatromanolaki A, Bates GJ, Koukourakis MI, Sivridis E, Gatter KC, Harris AL, Banham AH. The presence of tumor-infiltrating FOXP3+ lymphocytes correlates with intratumoral angiogenesis in endometrial cancer. Gynecol Oncol. 2008;110:216-21.
- 28. Yamagami W, Susumu N, Tanaka H, Hirasawa A, Banno K, Suzuki N, Tsuda H, Tsukazaki K, Aoki D. Immunofluorescence- detected infiltration of CD4+FOXP3+ regulatory T cells is relevant to the prognosis of patients with endometrial cancer. Int J Gynecol Cancer. 2011;21:1628-34.
- 29. Jiang XF, Tang QL, Shen XM, Li HG, Chen LH, Wang XY, Luo X, Lin ZQ, Jiang GY. Tumor-associated macrophages, epidermal growth factor receptor correlated with the triple negative phenotype in endometrial endometrioid adenocarcinoma. Pathol Res Pract. 2012;208:730-5.
- 30. Kondratiev S, Sabo E, Yakirevich E, Lavie O, Resnick MB. Intratumoral CD8+ T lymphocytes as a prognostic factor of survival in endometrial carcinoma. Clin Cancer Res. 2004;10:4450-6.
- 31. Cermakova P, Melichar B, Tomsova M, Zoul Z, Kalabova H, Spacek J, Dolezel M. Prognostic significance of CD3+ tumor- infiltrating lymphocytes in patients with endometrial carcinoma. Anticancer Res. 2014;34:5555-61.
- 32. Ino K, Yamamoto E, Shibata K, Kajiyama H, Yoshida N, Terauchi M, Nawa A, Nagasaka T, Takikawa O, Kikkawa F. Inverse correlation between tumoral indoleamine 2,3-dioxygenase expression and tumor-infiltrating lymphocytes in endometrial cancer: Its association with disease progression and survival. Clin Cancer Res. 2008;14:2310-7.
- 33. Colombo N, Creutzberg C, Amant F, Bosse T, González-Martín A, Ledermann J, Marth C, Nout R, Querleu D, Mirza MR, Sessa C; ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, treatment and follow-up. Ann Oncol. 2016;27:16-41.
- 34. Vargas R, Rauh-Hain JA, Clemmer J, Clark RM, Goodman A, Growdon WB, Schorge JO, Del Carmen MG, Horowitz NS, Boruta DM 2nd. Tumor size, depth of invasion, and histologic grade as prognostic factors of lymph node involvement in endometrial cancer: A SEER analysis. Gynecol Oncol. 2014;133:216-20.
- 35. How J, Gotlieb WH, Press JZ, Abitbol J, Pelmus M, Ferenczy A, Probst S, Gotlieb R, Brin S, Lau S. Comparing indocyanine green, technetium, and blue dye for sentinel lymph node mapping in endometrial cancer. Gynecol Oncol. 2015;137:436-42.
| APA | Öztürk Ç, Askan G, DUMAN ÖZTÜRK S, okcu o, Şen B, Bedir R (2023). High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients. , 75 - 82. 10.5146/tjpath.2022.01596 |
| Chicago | Öztürk Çiğdem,Askan Gokce,DUMAN ÖZTÜRK Seda,okcu oguzhan,Şen Bayram,Bedir Recep High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients. (2023): 75 - 82. 10.5146/tjpath.2022.01596 |
| MLA | Öztürk Çiğdem,Askan Gokce,DUMAN ÖZTÜRK Seda,okcu oguzhan,Şen Bayram,Bedir Recep High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients. , 2023, ss.75 - 82. 10.5146/tjpath.2022.01596 |
| AMA | Öztürk Ç,Askan G,DUMAN ÖZTÜRK S,okcu o,Şen B,Bedir R High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients. . 2023; 75 - 82. 10.5146/tjpath.2022.01596 |
| Vancouver | Öztürk Ç,Askan G,DUMAN ÖZTÜRK S,okcu o,Şen B,Bedir R High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients. . 2023; 75 - 82. 10.5146/tjpath.2022.01596 |
| IEEE | Öztürk Ç,Askan G,DUMAN ÖZTÜRK S,okcu o,Şen B,Bedir R "High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients." , ss.75 - 82, 2023. 10.5146/tjpath.2022.01596 |
| ISNAD | Öztürk, Çiğdem vd. "High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients". (2023), 75-82. https://doi.org/10.5146/tjpath.2022.01596 |
| APA | Öztürk Ç, Askan G, DUMAN ÖZTÜRK S, okcu o, Şen B, Bedir R (2023). High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients. Türk Patoloji Dergisi, 39(1), 75 - 82. 10.5146/tjpath.2022.01596 |
| Chicago | Öztürk Çiğdem,Askan Gokce,DUMAN ÖZTÜRK Seda,okcu oguzhan,Şen Bayram,Bedir Recep High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients. Türk Patoloji Dergisi 39, no.1 (2023): 75 - 82. 10.5146/tjpath.2022.01596 |
| MLA | Öztürk Çiğdem,Askan Gokce,DUMAN ÖZTÜRK Seda,okcu oguzhan,Şen Bayram,Bedir Recep High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients. Türk Patoloji Dergisi, vol.39, no.1, 2023, ss.75 - 82. 10.5146/tjpath.2022.01596 |
| AMA | Öztürk Ç,Askan G,DUMAN ÖZTÜRK S,okcu o,Şen B,Bedir R High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients. Türk Patoloji Dergisi. 2023; 39(1): 75 - 82. 10.5146/tjpath.2022.01596 |
| Vancouver | Öztürk Ç,Askan G,DUMAN ÖZTÜRK S,okcu o,Şen B,Bedir R High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients. Türk Patoloji Dergisi. 2023; 39(1): 75 - 82. 10.5146/tjpath.2022.01596 |
| IEEE | Öztürk Ç,Askan G,DUMAN ÖZTÜRK S,okcu o,Şen B,Bedir R "High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients." Türk Patoloji Dergisi, 39, ss.75 - 82, 2023. 10.5146/tjpath.2022.01596 |
| ISNAD | Öztürk, Çiğdem vd. "High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients". Türk Patoloji Dergisi 39/1 (2023), 75-82. https://doi.org/10.5146/tjpath.2022.01596 |
