title: Quantitative histology analysis of the ovarian tumour microenvironment.
abstract: Concerted efforts in genomic studies examining RNA transcription and DNA methylation patterns have revealed profound insights in prognostic ovarian cancer subtypes. On the other hand, abundant histology slides have been generated to date, yet their uses remain very limited and largely qualitative. Our goal is to develop automated histology analysis as an alternative subtyping technology for ovarian cancer that is cost-efficient and does not rely on DNA quality. We developed an automated system for scoring primary tumour sections of 91 late-stage ovarian cancer to identify single cells. We demonstrated high accuracy of our system based on expert pathologists' scores (cancer = 97.1%, stromal = 89.1%) as well as compared to immunohistochemistry scoring (correlation = 0.87). The percentage of stromal cells in all cells is significantly associated with poor overall survival after controlling for clinical parameters including debulking status and age (multivariate analysis p = 0.0021, HR = 2.54, CI = 1.40-4.60) and progression-free survival (multivariate analysis p = 0.022, HR = 1.75, CI = 1.09-2.82). We demonstrate how automated image analysis enables objective quantification of microenvironmental composition of ovarian tumours. Our analysis reveals a strong effect of the tumour microenvironment on ovarian cancer progression and highlights the potential of therapeutic interventions that target the stromal compartment or cancer-stroma signalling in the stroma-high, late-stage ovarian cancer subset.
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen University Cancer Centre, Guangzhou, China.|State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Lan
authors.affiliation: Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.|Centre for Molecular Pathology, The Royal Marsden Hospital, London, UK.|Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heindl
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen University Cancer Centre, Guangzhou, China.|State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China.|Department of Pathology, Sun Yat-sen University Cancer Centre, Guangzhou, China.
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Xi
authors.affiliation: Gynecology Unit, The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Susana
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen University Cancer Centre, Guangzhou, China.|State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.|Centre for Molecular Pathology, The Royal Marsden Hospital, London, UK.|Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001331:Automation; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D017154:Stromal Cells / Q000166:cytology; D015996:Survival Rate; D059016:Tumor Microenvironment