Abstract
BackgroundHigh 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.MethodsClinicopathological 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.ResultsTSR 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.ConclusionsLow 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.
Highlights
High tumour stromal content has been found to predict adverse clinical outcome in a range of epithelial tumours
Clinicopathological and follow-up data were collected for a retrospective series of 400 women in the Yorkshire area (UK) diagnosed with endometrial adenocarcinoma between 2005 and 2007 who had undergone a hysterectomy at our tertiary referral centre (St James’s University Hospital)
tumour-stroma ratio (TSR) could be viewed as an indirect measure of the stromal contribution to malignant progression, as suggested by studies showing an association between high tumour stromal content and adverse clinical outcome in colorectal [14, 17, 22, 25], oesophageal [15, 20], gastric [34] nasopharyngeal [26] breast [18, 19, 21, 23] hepatocellular [27], prostate [35] ovarian [16] and cervical [24] cancers
Summary
High tumour stromal content has been found to predict adverse clinical outcome in a range of epithelial tumours. ECs are broadly categorised into types I and II on Panayiotou et al BMC Cancer (2015) 15:955 cancers tend to affect older, post-menopausal women, follow a more aggressive clinical course and have a much poorer prognosis [5]. This classification model is an over-simplification since many endometrial cancers are not categorised neatly according to this dichotomy. Poorly differentiated, high grade EECs are frequently grouped with the NEECs for the purpose of treatment due to their poorer outcome, their prognosis in comparison to classical NEECs is debated [8,9,10,11]. There is a need to identify additional prognostic markers to achieve better patient stratification in the clinical management of endometrial cancer
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