Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

The prognostic significance of tumour-stroma ratio in endometrial carcinoma

Authors: Hannah Panayiotou, Nicolas M. Orsi, Helene H. Thygesen, Alexander I. Wright, Matthew Winder, Richard Hutson, Michele Cummings

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

High tumour stromal content has been found to predict adverse clinical outcome in a range of epithelial tumours. The aim of this study was to assess the prognostic significance of tumour-stroma ratio (TSR) in endometrial adenocarcinomas and investigate its relationship with other clinicopathological parameters.

Methods

Clinicopathological and 5-year follow-up data were obtained for a retrospective series of endometrial adenocarcinoma patients (n = 400). TSR was measured using a morphometric approach (point counting) on digitised histologic hysterectomy specimens. Inter-observer agreement was determined using Cohen’s Kappa statistic. TSR cut-offs were optimised using log-rank functions and prognostic significance of TSR on overall survival (OS) and disease-free survival (DFS) were determined using Cox Proportional Hazards regression analysis and Kaplan-Meier curves generated. Associations of TSR with other clinicopathological parameters were determined using non-parametric tests followed by Holm-Bonferroni correction for multiple comparisons.

Results

TSR as a continuous variable associated with worse OS (P = 0.034) in univariable Cox-regression analysis. Using the optimal cut-off TSR value of 1.3, TSR-high (i.e. low stroma) was associated with worse OS (HR = 2.51; 95 % CI = 1.22–5.12; P = 0.021) and DFS (HR = 2.19; 95 % CI = 1.15–4.17; P = 0.017) in univariable analysis. However, TSR did not have independent prognostic significance in multivariable analysis, when adjusted for known prognostic variables. A highly significant association was found between TSR and tumour grade (P < 0.001) and lymphovascular space invasion (P < 0.001), both of which had independent prognostic significance in this study population.

Conclusions

Low tumour stromal content associates with both poor outcome and with other adverse prognostic indicators in endometrial cancer, although it is not independently prognostic. These findings contrast with studies on many - although not all - cancers and suggest that the biology of tumour-stroma interactions may differ amongst cancer types.
Literature
1.
2.
3.
4.
Wright JD, Barrena Medel NI, Sehouli J, Fujiwara K, Herzog TJ. Contemporary management of endometrial cancer. Lancet. 2012;379(9823):1352–60.PubMedCrossRef
5.
Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I. Endometrial cancer. Lancet. 2005;366(9484):491–505.PubMedCrossRef
6.
Llauradó M, Ruiz A, Majem B, Ertekin T, Colás E, Pedrola N, et al. Molecular bases of endometrial cancer: new roles for new actors in the diagnosis and the therapy of the disease. Mol Cell Endocrinol. 2012;358(2):244–55.PubMedCrossRef
7.
8.
Boruta 2nd DM, Gehrig PA, Groben PA, Bae-Jump V, Boggess JF, Fowler Jr WC, et al. Uterine serous and grade 3 endometrioid carcinomas: is there a survival difference? Cancer. 2004;101(10):2214–21.PubMedCrossRef
9.
Hamilton CA, Cheung MK, Osann K, Chen L, Teng NN, Longacre TA, et al. Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer. 2006;94(5):642–6.PubMedCentralPubMed
10.
Soslow RA, Bissonnette JP, Wilton A, Ferguson SE, Alektiar KM, Duska LR, et al. Clinicopathologic analysis of 187 high-grade endometrial carcinomas of different histologic subtypes: similar outcomes belie distinctive biologic differences. Am J Surg Pathol. 2007;31(7):979–87.PubMedCrossRef
11.
Voss MA, Ganesan R, Ludeman L, McCarthy K, Gornall R, Schaller G, et al. Should grade 3 endometrioid endometrial carcinoma be considered a type 2 cancer-a clinical and pathological evaluation. Gynecol Oncol. 2012;124(1):15–20.PubMedCrossRef
12.
Geels YP, Pijnenborg JM, van den Berg-van Erp SH, Bulten J, Visscher DW, Dowdy SC, et al. Endometrioid endometrial carcinoma with atrophic endometrium and poor prognosis. Obstet Gynecol. 2012;120(5):1124–31.PubMed
13.
14.
Mesker WE, Junggeburt JMC, Szuhai K, de Heer P, Morreau H, Tanke HJ, et al. The carcinoma–stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage. Cell Oncol. 2007;29(5):387–98.PubMed
15.
Courrech Staal EF, Wouters MW, van Sandick JW, Takkenberg MM, Smit VT, Junggeburt J, et al. The stromal part of adenocarcinomas of the oesophagus: does it conceal targets for therapy? Eur J Cancer. 2010;46(4):720–8.PubMedCrossRef
16.
Labiche A, Heutte N, Herlin P, Chasle J, Gauduchon P, Elie N. Stromal compartment as a survival prognostic factor in advanced ovarian carcinoma. Int J Gynecol Cancer. 2010;20(1):28–33.PubMedCrossRef
17.
West NP, Dattani M, McShane P, Hutchins G, Grabsch J, Mueller W, et al. The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer. 2010;102(10):1519–23.PubMedCentralPubMedCrossRef
18.
de Kruijf EM, van Nes JG, van de Velde CJ, Putter H, Smit VT, Liefers GJ, et al. Tumor–stroma ratio in the primary tumor is a prognostic factor in early breast cancer patients, especially in triple-negative carcinoma patients. Breast Cancer Res Treat. 2011;125(3):687–96.PubMedCrossRef
19.
Moorman A, Vink R, Heijmans H, van der Palen J, Kouwenhoven E. The prognostic value of tumour-stroma ratio in triple-negative breast cancer. Eur J Surg Oncol. 2012;38(4):307–13.PubMedCrossRef
20.
Wang K, Ma W, Wang J, Yu L, Zhang X, Wang Z, et al. Tumor-stroma ratio is an independent predictor for survival in esophageal squamous cell carcinoma. J Thorac Oncol. 2012;7(9):1457–61.PubMedCrossRef
21.
Dekker T, van de Velde C, van Pelt G, Kroep J, Julien J, Smit V, et al. Prognostic significance of the tumor-stroma ratio: validation study in node-negative premenopausal breast cancer patients from the EORTC perioperative chemotherapy (POP) trial (10854). Breast Cancer Res Treat. 2013;139(2):371–9.PubMedCrossRef
22.
Huijbers A, Tollenaar RAEM, Pelt GW V, Zeestraten ECM, Dutton S, McConkey CC, et al. The proportion of tumor-stroma as a strong prognosticator for stage II and III colon cancer patients: validation in the VICTOR trial. Ann Oncol. 2013;24:179–85.PubMedCrossRef
23.
Gujam FJ, Edwards J, Mohammed ZM, Going JJ, McMillan DC. The relationship between the tumour stroma percentage, clinicopathological characteristics and outcome in patients with operable ductal breast cancer. Br J Cancer. 2014;111(1):157–65.PubMedCentralPubMedCrossRef
24.
Liu J, Liu J, Li J, Chen Y, Guan X, Wu X, et al. Tumor-stroma ratio is an independent predictor for survival in early cervical carcinoma. Gynecol Oncol. 2014;132(1):81–6.PubMedCrossRef
25.
Park JH, Richards CH, McMillan DC, Horgan PG, Roxburgh CS. The relationship between tumour stroma percentage, the tumour microenvironment and survival in patients with primary operable colorectal cancer. Ann Oncol. 2014;25(3):644–51.PubMedCentralPubMedCrossRef
26.
Zhang XL, Jiang C, Zhang ZX, Liu F, Zhang F, Cheng YF. The tumor-stroma ratio is an independent predictor for survival in nasopharyngeal cancer. Oncol Res Treat. 2014;37(9):480–4.PubMedCrossRef
27.
Lv Z, Cai X, Weng X, Xiao H, Du C, Cheng J, et al. Tumor-stroma ratio is a prognostic factor for survival in hepatocellular carcinoma patients after liver resection or transplantation. Surgery. 2015;158(1):142–50.PubMedCrossRef
28.
Creasman W. Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet. 2009;105(2):109.PubMedCrossRef
29.
30.
Downey C, Simpkins S, White J, Holliday D, Jones J, Jordan L, et al. The prognostic significance of tumour–stroma ratio in oestrogen receptor-positive breast cancer. Br J Cancer. 2014;110(7):1744–7.PubMedCentralPubMedCrossRef
31.
32.
Briët JM, Hollema H, Reesink N, Aalders JG, Mourits MJ, ten Hoor KA, et al. Lymphvascular space involvement: an independent prognostic factor in endometrial cancer. Gynecol Oncol. 2005;96(3):799–804.PubMedCrossRef
33.
Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012;21(3):309–22.PubMedCrossRef
34.
Wu Y, Grabsch H, Ivanova T, Tan IB, Murray J, Ooi CH, et al. Comprehensive genomic meta-analysis identifies intra-tumoural stroma as a predictor of survival in patients with gastric cancer. Gut. 2013;62(8):1100–11.PubMedCrossRef
35.
Yanagisawa N, Li R, Rowley D, Liu H, Kadmon D, Miles BJ, et al. Stromogenic prostatic carcinoma pattern (carcinomas with reactive stromal grade 3) in needle biopsies predicts biochemical recurrence-free survival in patients after radical prostatectomy. Hum Pathol. 2007;38(11):1611–20.PubMedCrossRef
36.
Bever KM, Sugar EA, Bigelow E, Sharma R, Laheru D, Wolfgang CL, et al. The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy. HPB (Oxford). 2015;17(4):292–8.CrossRef
37.
38.
39.
Cirri P, Chiarugi P. Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression. Cancer Metastasis Rev. 2012;31:195–208.PubMedCrossRef
40.
Özdemir BC, Pentcheva-Hoang T, Carstens JL, Zheng X, Wu CC, Simpson TR, et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014;25(6):719–34.PubMedCentralPubMedCrossRef
41.
Rhim AD, Oberstein PE, Thomas DH, Mirek ET, Palermo CF, Sastra SA, et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014;25(6):735–47.PubMedCentralPubMedCrossRef
42.
Subramaniam KS, Tham ST, Mohamed Z, Woo YL, Mat Adenan NA, Chung I. Cancer-associated fibroblasts promote proliferation of endometrial cancer cells. PLoS One. 2013;8(7):e68923.PubMedCentralPubMedCrossRef
43.
Aprelikova O, Palla J, Hibler B, Yu X, Greer YE, Yi M, et al. Silencing of miR-148a in cancer-associated fibroblasts results in WNT10B-mediated stimulation of tumor cell motility. Oncogene. 2013;32(27):3246–53.PubMedCentralPubMedCrossRef
44.
Espinosa I, Catasus L, D’ Angelo E, Mozos A, Pedrola N, Bértolo C, et al. Stromal signatures in endometrioid endometrial carcinomas. Mod Pathol. 2014;27(4):631–9.PubMedCrossRef
Metadata
Title
The prognostic significance of tumour-stroma ratio in endometrial carcinoma
Authors
Hannah Panayiotou
Nicolas M. Orsi
Helene H. Thygesen
Alexander I. Wright
Matthew Winder
Richard Hutson
Michele Cummings
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1981-7

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue

Study protocol

A randomized phase II study of weekly nab-paclitaxel plus gemcitabine or simplified LV5FU2 as first-line therapy in patients with metastatic pancreatic cancer: the AFUGEM GERCOR trial

Research article

Local control in metastatic neuroblastoma in children over 1 year of age

Study protocol

eCROPS-CA: a systematic approach toward effective and sustainable cancer prevention in rural China

Research article

Critical role of CDK11p58 in human breast cancer growth and angiogenesis

Research article

The pretreatment albumin to globulin ratio predicts chemotherapeutic outcomes in patients with unresectable metastatic colorectal cancer

Research article

Leucopenia and treatment efficacy in advanced nasopharyngeal carcinoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits