Systematic study of tissue factor expression in solid tumors

被引:20
作者
de Bono, Johann S. [1 ]
Harris, Jeffrey R. [2 ]
Burm, Saskia M. [3 ]
Vanderstichele, Adriaan [4 ]
Houtkamp, Mischa A. [3 ]
Aarass, Saida [2 ,3 ]
Riisnaes, Ruth [1 ]
Figueiredo, Ines [1 ]
Rodrigues, Daniel Nava [1 ]
Christova, Rossitza [1 ]
Olbrecht, Siel [4 ]
Niessen, Hans W. M. [5 ]
Ruuls, Sigrid R. [6 ]
Schuurhuis, Danita H. [3 ]
van Bueren, Jeroen J. Lammerts [7 ]
Breij, Esther C. W. [3 ]
Vergote, Ignace [4 ]
机构
[1] Royal Canc Hosp, Inst Canc Res, London, England
[2] Genmab, Plainsboro, NJ USA
[3] Genmab, Utrecht, Netherlands
[4] Univ Hosp Leuven, Leuven Canc Inst, Dept Gynaecol & Obstet, Div Gynaecol Oncol, Leuven, Belgium
[5] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands
[6] Lava Therapeut, Utrecht, Netherlands
[7] Merus, Utrecht, Netherlands
关键词
biopsies expression; immunohistochemistry; solid tumor; targeted therapy; tissue factor; CANCER; PROGRESSION; HEMOSTASIS; SURVIVAL; GROWTH; TF;
D O I
10.1002/cnr2.1699
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Elevated tissue factor (TF) expression, although restricted in normal tissue, has been reported in multiple solid cancers, and expression has been associated with poor prognosis. This manuscript compares TF expression across various solid tumor types via immunohistochemistry in a single study, which has not been performed previously. Aims To increase insight in the prevalence and cellular localization of TF expression across solid cancer types, we performed a detailed and systematic analysis of TF expression in tumor tissue obtained from patients with ovarian, esophageal, bladder, cervical, endometrial, pancreatic, prostate, colon, breast, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and glioblastoma. The spatial and temporal variation of TF expression was analyzed over time and upon disease progression in patient-matched biopsies taken at different timepoints. In addition, TF expression in patient-matched primary tumor and metastatic lesions was also analyzed. Methods and Results TF expression was detected via immunohistochemistry (IHC) using a validated TF-specific antibody. TF was expressed in all cancer types tested, with highest prevalence in pancreatic cancer, cervical cancer, colon cancer, glioblastoma, HNSCC, and NSCLC, and lowest in breast cancer. Staining was predominantly membranous in pancreatic, cervical, and HNSCC, and cytoplasmic in glioblastoma and bladder cancer. In general, expression was consistent between biopsies obtained from the same patient over time, although variability was observed for individual patients. NSCLC biopsies of primary tumor and matched lymph node metastases showed no clear difference in TF expression overall, although individual patient changes were observed. Conclusion This study shows that TF is expressed across a broad range of solid cancer types, and expression is present upon tumor dissemination and over the course of treatment.
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页数:11
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