Association between tumour infiltrating lymphocytes, histotype and clinical outcome in epithelial ovarian cancer

Background There is evidence that some ovarian tumours evoke an immune response, which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a standardised method for their H&E visual evaluation has been validated in breast cancer. Met...

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Vydané v:BMC cancer Ročník 17; číslo 1; s. 657 - 7
Hlavní autori: James, Fiona R., Jiminez-Linan, Mercedes, Alsop, Jennifer, Mack, Marie, Song, Honglin, Brenton, James D., Pharoah, Paul D. P., Ali, H. Raza
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London BioMed Central 20.09.2017
BioMed Central Ltd
Springer Nature B.V
BMC
Predmet:
Apoptosis
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Care and treatment
Case-Control Studies
Clinical outcomes
Development and progression
Epithelial ovarian cancer
Fatalities
Female
Genetic aspects
Health Promotion and Disease Prevention
Histological subtype
Humans
Immune response
Invasiveness
Ligands
Lymphocytes
Lymphocytes, Tumor-Infiltrating - pathology
Medical prognosis
Medicine/Public Health
Metastases
Middle Aged
Mutation
Neoplasms, Glandular and Epithelial - immunology
Neoplasms, Glandular and Epithelial - mortality
Neoplasms, Glandular and Epithelial - secondary
Neoplasms, Glandular and Epithelial - therapy
Oncology
Ovarian cancer
Ovarian Neoplasms - immunology
Ovarian Neoplasms - mortality
Ovarian Neoplasms - pathology
Ovarian Neoplasms - therapy
Patient outcomes
Patients
Physiological aspects
Population studies
Prognosis
Proportional Hazards Models
Research Article
Standardised method
Statistical analysis
Studies
Surgical Oncology
Survival time
Translational oncology
Treatment Outcome
Tumors
Tumour infiltrating lymphocytes (TILs)
United Kingdom
Tumour infiltrating lymphocytes (TILs)
Histological subtype
Epithelial ovarian cancer
Survival time
Standardised method
ISSN:1471-2407, 1471-2407
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Shrnutí:Background There is evidence that some ovarian tumours evoke an immune response, which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a standardised method for their H&E visual evaluation has been validated in breast cancer. Methods We sought to investigate the prognostic significance of TILs in a study of 953 invasive epithelial ovarian cancer tumour samples, both primary and metastatic, from 707 patients from the prospective population-based SEARCH study. TILs were analysed using a standardised method based on H&E staining producing a percentage score for stromal and intratumoral compartments. We used Cox regression to estimate hazard ratios of the association between TILs and survival. Results The extent of stromal and intra-tumoral TILs were correlated in the primary tumours ( n  = 679, Spearman’s rank correlation = 0.60, P  < 0.001) with a similar correlation in secondary tumours ( n  = 224, Spearman’s rank correlation = 0.62, P  < 0.001). There was a weak correlation between stromal TIL levels in primary and secondary tumour samples (Spearman’s rank correlation = 0.29, P  < 0.001) and intra-tumoral TIL levels in primary and secondary tumour samples (Spearman’s rank correlation = 0.19, P  = 0.0094). The extent of stromal TILs differed between histotypes (Pearson chi2 (12d.f.) 54.1, P  < 0.0001) with higher levels of stromal infiltration in the high-grade serous and endometriod cases. A significant association was observed for higher intratumoral TIL levels and a favourable prognosis (HR 0.74 95% CI 0.55–1.00 p  = 0.047). Conclusion This study is the largest collection of epithelial ovarian tumour samples evaluated for TILs. We have shown that stromal and intratumoral TIL levels are correlated and that their levels correlate with clinical variables such as tumour histological subtype. We have also shown that increased levels of both intratumoral and stromal TILs are associated with a better prognosis; however, this is only statistically significant for intratumoral TILs. This study suggests that a clinically useful immune prognostic indicator in epithelial ovarian cancer could be developed using this technique.
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ISSN:1471-2407
1471-2407
DOI:10.1186/s12885-017-3585-x