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B7–H3 Ligand Expression by Primary Breast Cancer and Associated With Regional Nodal Metastasis

Arigami, Takaaki MD, PhD*; Narita, Norihiko MD, PhD*; Mizuno, Ryuichi MD, PhD*; Nguyen, Linhda BS*; Ye, Xing MSc; Chung, Alice MD; Giuliano, Armando E. MD; Hoon, Dave S. B. MSc, PhD*

doi: 10.1097/SLA.0b013e3181f1939d
Original Articles: ORIGINAL STUDY

Objective: B7 ligand family members have been shown to be important immunoregulatory factors in host tumor immune responses. We hypothesized that B7–H3, a coinhibitory factor, is expressed by primary breast cancer cells and associated with metastasis to regional tumor-draining lymph nodes.

Experimental Design: American Joint Committee on Cancer stage I to III primary breast cancers (n = 82) and normal breast specimens (n = 17) were assessed for B7–H3 expression using paraffin-embedded archival tissues. B7–H3 expression by breast cancer cells was assessed by a quantitative real-time reverse transcription-polymerase chain reaction, and B7–H3 protein expression was evaluated using immunohistochemistry.

Results: B7–H3 mRNA expression was detected in 32 of 82 (39%) primary breast tumors but not in normal breast tissues (P = 0.0029). B7–H3 expression in primary tumors significantly correlated with increasing tumor size, American Joint Committee on Cancer stage, and lymphovascular invasion (P < 0.0001, P < 0.0001, P = 0.0071). B7–H3 expression was highly correlated to sentinel lymph node and overall number of lymph nodes with metastasis P = 0.003, and P = 0.004, respectively). In a multivariate analysis, B7–H3 mRNA expression of the primary tumor significantly predicted metastasis to regional lymph nodes (P = 0.021, and P = 0.023, respectively). Antibody staining analysis of paraffin-embedded archival tissue breast tumors and flow cytometry of breast cancer cell lines demonstrated B7–H3 protein expression.

Conclusions: B7–H3 protein expressed by primary breast cancer cells is a tumor progression factor and is associated with extent of regional nodal metastasis.

Prediction of extent of regional nodal metastasis in breast cancer patients on primary tumor diagnosis would identify high-risk patients. B7-H3 a protein associated with immune tolerance was identified in breast cancer cells. The presence of B7-H3 in breast primary tumors is associated with advances to regional nodal metastasis.

*Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, CA;

Division of Biostatistics Research, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, CA.

Breast Center, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, CA.

Supported from Susan G. Komen Breast Cancer Foundation grant BCTR0707528, Associate for Breast and Prostate Cancer Studies (Beverly Hills, CA), and Leslie and Susan Gonda (Goldschmied) Foundation (Los Angeles, CA).

Reprints: Dave S. B. Hoon, PhD, Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404. E-mail:

© 2010 Lippincott Williams & Wilkins, Inc.