EGAGenomicsAperioOtherhttps://ega-archive.org/studies/EGAS00001002065EGAEGA study EGAS00001002065OvCan2EGArestrictedThe tumor microenvironment is pivotal in influencing cancer progression and metastasis. Different cells co-exist with high spatial diversity within a patient, yet their combinatorial effects are poorly understood. We investigate the similarity of the tumor microenvironment of 192 local metastatic lesions in 61 ovarian cancer patients. An ecologically inspired measure of microenvironmental diversity derived from multiple metastasis sites is correlated with clinicopathological characteristics and prognostic outcome. We demonstrate a high accuracy of our automated analysis across multiple sites. A low level of similarity in microenvironmental composition is observed between ovary tumor and corresponding local metastases (stromal ratio r = 0.30, lymphocyte ratio r = 0.37). We identify a new measure of microenvironmental diversity derived from Shannon entropy that is highly predictive of poor overall (p = 0.002, HR = 3.18, 95% CI = 1.51-6.68) and progression-free survival (p = 0.0036, HR = 2.83, 95% CI = 1.41-5.7), independent of and stronger than clinical variables, subtype stratifications based on single cell types alone and number of sites. Although stromal influence in ovary tumors is known to have significant clinical implications, our findings reveal an even stronger impact orchestrated by diverse cell types. Quantitative histology-based measures can further enable objective selection of patients who are in urgent need of new therapeutic strategies such as combinatorial treatments targeting heterogeneous tumor microenvironment.Similarity and diversity of the tumor microenvironment in multiple metastases: critical implications for overall and progression-free survival of high-grade serous ovarian cancer.Heindl Andreas A, Lan Chunyan C, Rodrigues Daniel Nava DN, Koelble Konrad K, Yuan Yinyin YCancer Microenvironments, Progression-Free, Cancer Microenvironment, Event Free Survival, Microenvironment, Survival, malignant ovarian serous tumour, serous ovarian cancer., Event-Free Survival, Event-Free, Tumor Microenvironments, Tumor, Microenvironments, Progression Free Survival, CancerOvary Cancer, d230, determination, Microenvironment, Metastasis, selection process, Neoplasms, ovary tumor, Benign Neoplasm, number, histology, tumor of ovary, dTAFII250, Neoplasm Metastases, neoplasm of ovary, neoplasm metastasis, Tumor, Malignant, EfW1, Ximpact, presence, cancer metastasis, gonada of female organism genitalia, dmTAF[[II]]230, OVARIAN NEOPL, malignant tumour of ovary, ovarian tumors, morphology, ovarian cancer, gonad of genitalia of female organism, Cancer Microenvironment, Ovarian, dmTAF1, Taf230, Survival, Genetic heterogeneity, symptoms, Low, Event-Free Survival, Tumor Microenvironments, anatomy and histology, TAF250, genitalia of female organism gonada, imprinted and ancient gene protein, tumor cell migration, OVARY NEOPL, Taf200, me75, gonada of female organism reproductive system, anatomy, dTAF[[II]]250, TFIID TAF250, Malignancy, cel, cell, genitalia of female organism gonad, ovum-producing ovary, Ovarian Cancer, female organism reproductive system gonad, metastasis, Taf1p, Event-Free, D17Mit170, primary ovarian cancer, T1, NEOPL OVARIAN, Neoplasias, dTAF250, reproductive system of female organism gonada, reproductive system of female organism gonad, malignant neoplasm, Event Free Survival, Clients, Therapies, ovary - animal, ovary, Malignancies, Lymphoid, Ovarian Cancers, TAF, female organism genitalia gonad, tumor metastasis, female reproductive system gonada, Lymphocyte, Cancer, Tumors, Cancer Microenvironments, Therapy, screening, Cancer of Ovary, dTAF[[II]]230, TAF[[II]]250, gonad of female reproductive system, findings, Malignant Neoplasm, cou, Cancer., ovarian neoplasm, ovary neoplasm (disease), gonada of reproductive system of female organism, gonad of female organism reproductive system, tumor of the ovary, gonada of female reproductive system, Metastases, Ovary, TAF200, l(3)84Ab, BG:DS00004.13, TAFII-250, Tl3, TAF250/230, Ovary Cancers, Tl2, Client, Cell, impact-a, Progression Free Survival, dTAF230, Metastase, count in organism, TAFII250, Lr, MT, Benign, epithelial, Ovaries, p230, malignant Ovarian tumor, chemical analysis, Neoplasm, TAF[[II]]250/230, TFIID, imprinted and ancient gene protein homolog, IMPACT, Lymphoid Cell, female reproductive system gonad, Lymphoid Cells, Ovary Neoplasm, Progression-Free, Taf[[II]]250, Cancer of the Ovary, ovaries, female organism reproductive system gonada, primary cancer, animal ovary, TAF[[II]]230, histopathology, gonada of genitalia of female organism, female gonad, Heterogeneity, ovarium, gonad of reproductive system of female organism, ovarian epithelial cancer, signs, Benign Neoplasms, OC, gonad of female organism genitalia, patient, Ovary Neoplasms, TAF[II]250, Cancers, CG17603, Ovarian Neoplasms, TAF[[II]], malignant tumor, Treatments, ovary neoplasm, ovarian tumor, Malignant Neoplasms, metastatic, DmelCG17603, Ovarian Neoplasm, female organism genitalia gonada, Patient, Taf250, Therapeutic, tumor of the Ovary, neoplasm of the ovary, SR3-5, Cells, cardinality, Bra, Entropies, Treatment, assay, E430016J11Rik, Microenvironments, Neoplasia, RWDD5, TAF230, TAF1Cancer Microenvironments, Progression-Free, Cancer Microenvironment, Event Free Survival, Microenvironment, Survival, malignant ovarian serous tumour, serous ovarian cancer., Event-Free Survival, Event-Free, Tumor Microenvironments, Tumor, Microenvironments, Progression Free Survival, CancerOvary Cancer, d230, determination, Microenvironment, Metastasis, selection process, Neoplasms, ovary tumor, Benign Neoplasm, number, histology, tumor of ovary, dTAFII250, Neoplasm Metastases, neoplasm of ovary, neoplasm metastasis, Tumor, Malignant, EfW1, Ximpact, presence, cancer metastasis, gonada of female organism genitalia, dmTAF[[II]]230, OVARIAN NEOPL, malignant tumour of ovary, ovarian tumors, morphology, ovarian cancer, gonad of genitalia of female organism, Cancer Microenvironment, Ovarian, dmTAF1, Taf230, Survival, Genetic heterogeneity, symptoms, Low, Event-Free Survival, Tumor Microenvironments, anatomy and histology, TAF250, genitalia of female organism gonada, imprinted and ancient gene protein, tumor cell migration, OVARY NEOPL, Taf200, me75, gonada of female organism reproductive system, anatomy, dTAF[[II]]250, TFIID TAF250, Malignancy, cel, cell, genitalia of female organism gonad, ovum-producing ovary, Ovarian Cancer, female organism reproductive system gonad, metastasis, Taf1p, Event-Free, D17Mit170, primary ovarian cancer, T1, NEOPL OVARIAN, Neoplasias, dTAF250, reproductive system of female organism gonada, reproductive system of female organism gonad, malignant neoplasm, Event Free Survival, Clients, Therapies, ovary - animal, ovary, Malignancies, Lymphoid, Ovarian Cancers, TAF, female organism genitalia gonad, tumor metastasis, female reproductive system gonada, Lymphocyte, Cancer, Tumors, Cancer Microenvironments, Therapy, screening, Cancer of Ovary, dTAF[[II]]230, TAF[[II]]250, gonad of female reproductive system, findings, Malignant Neoplasm, cou, Cancer., ovarian neoplasm, ovary neoplasm (disease), gonada of reproductive system of female organism, gonad of female organism reproductive system, tumor of the ovary, gonada of female reproductive system, Metastases, Ovary, TAF200, l(3)84Ab, BG:DS00004.13, TAFII-250, Tl3, TAF250/230, Ovary Cancers, Tl2, Client, Cell, impact-a, Progression Free Survival, dTAF230, Metastase, count in organism, TAFII250, Lr, MT, Benign, epithelial, Ovaries, p230, malignant Ovarian tumor, chemical analysis, Neoplasm, TAF[[II]]250/230, TFIID, imprinted and ancient gene protein homolog, IMPACT, Lymphoid Cell, female reproductive system gonad, Lymphoid Cells, Ovary Neoplasm, Progression-Free, Taf[[II]]250, Cancer of the Ovary, ovaries, female organism reproductive system gonada, primary cancer, animal ovary, TAF[[II]]230, histopathology, gonada of genitalia of female organism, female gonad, Heterogeneity, ovarium, gonad of reproductive system of female organism, ovarian epithelial cancer, signs, Benign Neoplasms, OC, gonad of female organism genitalia, patient, Ovary Neoplasms, TAF[II]250, Cancers, CG17603, Ovarian Neoplasms, TAF[[II]], malignant tumor, Treatments, ovary neoplasm, ovarian tumor, Malignant Neoplasms, metastatic, DmelCG17603, Ovarian Neoplasm, female organism genitalia gonada, Patient, Taf250, Therapeutic, tumor of the Ovary, neoplasm of the ovary, SR3-5, Cells, cardinality, Bra, Entropies, Treatment, assay, E430016J11Rik, Microenvironments, Neoplasia, RWDD5, TAF230, TAF1falseSimilarity and diversity of the tumor microenvironment in multiple metastases: critical implications for overall and progression-free survival of high-grade serous ovarian cancer.The tumor microenvironment is pivotal in influencing cancer progression and metastasis. Different cells co-exist with high spatial diversity within a patient, yet their combinatorial effects are poorly understood. We investigate the similarity of the tumor microenvironment of 192 local metastatic lesions in 61 ovarian cancer patients. An ecologically inspired measure of microenvironmental diversity derived from multiple metastasis sites is correlated with clinicopathological characteristics and prognostic outcome. We demonstrate a high accuracy of our automated analysis across multiple sites. A low level of similarity in microenvironmental composition is observed between ovary tumor and corresponding local metastases (stromal ratio r = 0.30, lymphocyte ratio r = 0.37). We identify a new measure of microenvironmental diversity derived from Shannon entropy that is highly predictive of poor overall (p = 0.002, HR = 3.18, 95% CI = 1.51-6.68) and progression-free survival (p = 0.0036, HR = 2.83, 95% CI = 1.41-5.7), independent of and stronger than clinical variables, subtype stratifications based on single cell types alone and number of sites. Although stromal influence in ovary tumors is known to have significant clinical implications, our findings reveal an even stronger impact orchestrated by diverse cell types. Quantitative histology-based measures can further enable objective selection of patients who are in urgent need of new therapeutic strategies such as combinatorial treatments targeting heterogeneous tumor microenvironment.2017-07-26 15:39:29EGAS00001002065960627661102EGAD00010001099EGAC00001000433