scholarly journals From High-Throughput Microarray-Based Screening to Clinical Application: The Development of a Second Generation Multigene Test for Breast Cancer Prognosis

Microarrays ◽  
2013 ◽  
Vol 2 (3) ◽  
pp. 243-264 ◽  
Author(s):  
Jan Brase ◽  
Ralf Kronenwett ◽  
Christoph Petry ◽  
Carsten Denkert ◽  
Marcus Schmidt
2021 ◽  
Author(s):  
Timothy Su ◽  
Shuyang Wang ◽  
Shuya Huang ◽  
Hui Cai ◽  
Eliot T. McKinley ◽  
...  

Abstract Purpose Tumor-infiltrating lymphocytes (TILs) have emerged as predictive biomarkers for cancer prognosis. The clinicopathological significance of spatial TIL subpopulations is not well studied due to lack of high-throughput scalable methodology for large population studies.Methods We established a fluorescent multiplex immunohistochemistry (mIHC) method coupled with computer-assisted high-throughput quantitative analysis. We then evaluated associations of six TILs markers (CD3, CD8, CD20, CD56, FOXP3, and PD-L1) with breast cancer prognosis among 188 tumor samples from the Nashville Breast Health Study. Results Our 5-plex fluorescent mIHC workflow was reliable, highly sensitive, non-interfering, and balanced labeling for three biomarkers per tissue section, which is applicable for high-throughput imaging quantification of spatial TILs in regular laboratory settings. In this study we found that the increased intratumoral CD56+ cells were associated with worse overall survival (OS) (HR, 4.89; 95% CI: 1.26-18.95, highest vs lowest tertiles; Ptrend = 0.022), suggesting the subset of immunosuppressive NK cell phenotypes within tumor bed. Increased stromal PD-L1+ cells (HR, 0.01; 95% CI, 0.00-0.89; Ptrend = 0.042) and a high stromal CD8+/FOXP3+ ratio (HR, 0.00; 95% CI, 0.00-0.12; Ptrend = 0.036) were associated with more favorable OS in stage III-IV breast cancer patients. Conclusion We established a reliable 5-plex fluorescent mIHC and showed that CD56+, PD-L1, and CD8+/FOXP3+ ratio may be important biomarkers for breast cancer prognosis. Further studies with a larger sample size are warrant to further elucidate the association between TILs and breast cancer outcomes.


2003 ◽  
Vol 105 (4) ◽  
pp. 542-545 ◽  
Author(s):  
Niels Kroman ◽  
Jan Wohlfahrt ◽  
Henning T. Mouridsen ◽  
Mads Melbye

1993 ◽  
Vol 47 (6-7) ◽  
pp. 256
Author(s):  
F. Di Carlo ◽  
S. Racca ◽  
G. Conti ◽  
M. Tampellini ◽  
F. Pietribiasi ◽  
...  

2012 ◽  
Vol 8 (6) ◽  
pp. 703-711 ◽  
Author(s):  
Masoud H Manjili ◽  
Kayvan Najarian ◽  
Xiang-Yang Wang

2006 ◽  
Vol 23 (1) ◽  
pp. 30-37 ◽  
Author(s):  
Yijun Sun ◽  
Steve Goodison ◽  
Jian Li ◽  
Li Liu ◽  
William Farmerie

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