Prognostic Significance of Lymphocyte Infiltration and a Stromal Immunostaining of a Bladder Cancer Associated Diagnostic Panel in Urothelial Carcinoma

被引：8

作者：

Furuya, Hideki ^{[1
,2
,3
]}

Chan, Owen T. M. ^{[1
]}

Hokutan, Kanani ^{[1
,2
]}

Tsukikawa, Yutaro ^{[1
]}

Chee, Keanu ^{[1
]}

Kozai, Landon ^{[4
]}

Chan, Keith S. ^{[5
]}

Dai, Yunfeng ^{[6
]}

Wong, Regan S. ^{[3
]}

Rosser, Charles J. ^{[1
,2
,3
]}

机构：

[1] Univ Hawaii, Clin & Translat Res Program, Canc Ctr, Honolulu, HI 96813 USA

[2] Univ Hawaii Manoa, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA

[3] Cedars Sinai Med Ctr, Dept Surg, Los Angeles, CA 90048 USA

[4] Univ Hawaii Manoa, John A Burn Sch Med, Honolulu, HI 96813 USA

[5] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA

[6] Univ Florida, Dept Biostat, Gainesville, FL 32611 USA

来源：

DIAGNOSTICS | 2020年 / 10卷 / 01期

关键词：

bladder cancer; stroma; lymphocyte; prognosis; BIOMARKER PANEL; METHYLATION; EXPRESSION; ANGIOGENESIS; CHEMOTHERAPY; PROGRESSION; VALIDATION;

D O I：

10.3390/diagnostics10010014

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页数：15

共 48 条

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