NY-ESO-1 protein expression in primary breast carcinoma and metastases: correlation with CD8+ T-cell and CD79a+ plasmacytic/B-cell infiltration.
NY-ESO-1 is a cancer testis antigen expressed in various malignancies and testicular germ cells. Because of its capacity to induce specific humoral and cellular immunity in patients with NY-ESO-1-positive carcinomas, it represents a promising target for cancer immunotherapy. In breast cancer, NY-ESO-1-mRNA was reported in up to 42%, but protein expression has not been determined to larger extent. In the present tissue microarray-based study, primary breast cancers (n = 1,444), in situ lesion (n = 148), recurrences (n = 88), lymph node (n = 525) and distant metastases (n = 91) were studied for NY-ESO-1 expression by immunohistochemistry. NY-ESO-1-protein expression was compared with mRNA expression by real-time PCR. NY-ESO-1-protein was detected in 3.1% (4/128) in situ lesions and in 2.1% (28/1355) invasive breast cancer. There were 1.8% (9/493) NY-ESO-1-positive lymph node and 5.1% (4/78) positive distant metastases. NY-ESO-1 was more frequently expressed in grade 3 (4.9%) than in grade 2 (0.8%) and grade 1 (0.5%) carcinomas (p < 0.0001). Presence of tumor-infiltrating CD8+ T-cells correlated with NY-ESO-1 (p < 0.0001) on the tissue microarray. On randomly selected large sections, 4 out of 9 NY-ESO-1-positive tumors displayed a brisk infiltrate of CD79a+ plasmocytes/B-cells, but none of 10 NY-ESO-1-negative tumors (p < 0.05). NY-ESO-1-mRNA expression was detected in frozen samples of NY-ESO-1-protein positive (n = 6) and negative breast cancers (n = 8) and in normal testis. Comparison between mRNA and protein expression revealed that only breast cancers with NY-ESO-1-mRNA levels comparable or higher than testis expressed NY-ESO-1-protein. These findings suggest that NY-ESO-1-positive breast cancers represent a small subset of poorly differentiated tumors with evidence of cellular and humoral immune response.
Theurillat
Jean-Philippe
JP
Department Pathology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. jean-philippe.theurillat@usz.ch
Ingold
Fabienne
F
Frei
Claudia
C
Zippelius
Alfred
A
Varga
Zsuzsanna
Z
Seifert
Burkhardt
B
Chen
Yao-Tseng
YT
Jäger
Dirk
D
Knuth
Alexander
A
Moch
Holger
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism*; D051925:CD79 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D000951:Antigens, Neoplasm; D051925:CD79 Antigens; C104948:CTAG1B protein, human; D008565:Membrane Proteins