| Autor: |
Furuya H; Clinical and Translational Research Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.; Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI 96822, USA.; Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA., Chan OTM; Clinical and Translational Research Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA., Hokutan K; Clinical and Translational Research Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.; Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI 96822, USA., Tsukikawa Y; Clinical and Translational Research Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA., Chee K; Clinical and Translational Research Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA., Kozai L; John A. Burn School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA., Chan KS; Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA., Dai Y; Department of Biostatistics, University of Florida, Gainesville, FL 32611, USA., Wong RS; Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA., Rosser CJ; Clinical and Translational Research Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.; Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI 96822, USA.; Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. |
| Abstrakt: |
We set out to expand on our previous work in which we reported the epithelial expression pattern of a urine-based bladder cancer-associated diagnostic panel (A1AT, ANG, APOE, CA9, IL8, MMP9, MMP10, PAI1, SDC1, and VEGFA). Since many of the analytes in the bladder cancer-associated diagnostic signature were chemokines, cytokines, or secreted proteins, we set out to report the stromal staining pattern of the diagnostic signature as well as CD3 + (T-cell) cell and CD68 + (macrophage) cell staining in human bladder tumors as a snapshot of the tumor immune landscape. Immunohistochemical staining was performed on 213 tumor specimens and 74 benign controls. Images were digitally captured and quantitated using Aperio (Vista, CA). The expression patterns were correlated with tumor grade, tumor stage, and outcome measures. We noted a positive correlation of seven of the 10 proteins (excluding A1AT and IL8 which had a negative association and VEGFA had no association) in bladder cancer. The overexpression of MMP10 was associated with higher grade disease, while overexpression of MMP10, PAI1, SDC1 and ANG were associated with high stage bladder cancer and CA9 was associated with low stage bladder cancer. Increased tumor infiltration of CD68 + cells were associated with higher stage disease. Overall survival was significantly reduced in bladder cancer patients' whose tumors expressed eight or more of the 10 proteins that comprise the bladder cancer diagnostic panel. These findings confirm that the chemokines, cytokines, and secreted proteins in a urine-based diagnostic panel are atypically expressed, not only in the epithelial component of bladder tumors, but also in the stromal component of bladder tumors and portends a worse overall survival. Thus, when assessing immunohistochemical staining, it is important to report staining patterns within the stroma as well as the entire stroma itself. |
