Expression and clinical significance of MAGE and NY-ESO-1 cancer-testis antigens in adenoid cystic carcinoma of the head and neck

Abstract

Background: Adenoid cystic carcinoma (ACC) of the head and neck is a rare but highly malignant tumor. Cancer-testis antigens (CTAs) represent an immunogenic family of cancer-specific proteins and thus represent an attractive target for immunotherapy.

Methods: Eighty-four cases of ACC were identified, the CTAs pan-Melanoma antigen (pan-MAGE; M3H67) and New York esophageal squamous cell carcinoma (NY-ESO-1; E978) were detected immunohistochemically (IHC) and correlated with clinical data.

Results: Expression of NY-ESO-1 was found in 48 of 84 patients (57.1%) and of pan-MAGE in 28 of 84 patients (31.2%). Median overall survival (OS) in NY-ESO-1 positive versus negative patients was 130.8 and 282.0 months (p = .223), respectively. OS in pan-MAGE positive versus negative patients was 105.3 and 190.5 months, respectively (p = .096). Patients expressing both NY-ESO-1 and pan-MAGE simultaneously had significantly reduced OS with a median of 90.5 months compared with 282.0 months in negative patients (p = .047).

Conclusion: A significant fraction of patients with ACC show expression of the CTAs NY-ESO-1 and/or pan-MAGE with promising immunotherapeutic implications. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1008-1016, 2016.

Keywords: Melanoma antigen; New York esophageal squamous cell carcinoma (NY-ESO-1); adenoid cystic carcinoma; cancer-testis antigens; head and neck cancer.

Figure 1

Analysis of overall survival (OS) of ACC patients based on known prognosticators: A: Perineural invasion: Pn1 = positive, Pn0 = negative (Pn). B: Resection margin status: R+ = positive resection margins, R0 = negative resection margins. C: Lymph node involvement: pN+ = positive lymph nodes, pN0 = negative lymph node involvement. D: Anatomical primary site of the tumor: MSG = primary tumor in the major salivary glands, OTH = primary tumor in a site other than the major salivary glands. E: Site of treatment failure: distant vs. local and/or regional. F: Histological growth pattern: Solid growth pattern vs. non-solid growth pattern (including tubular, cribriform and mixed histologic growth pattern).

Figure 2

Immunohistochemical staining of NY-ESO-1 (antibody E978): a) Negative control of parotid gland tissue. b) positive control staining of testicular tissue. c) negative staining of tumor tissue. d) weakly positive staining of tumor tissue with tubular growth pattern. e) moderately strong staining of ACC with solid growth pattern. f) strong expression of NY-ESO-1 in 50% of tumor tissue, stroma tissue is negative.

Figure 3

Immunohistochemical staining of pan-MAGE (M3H67 antibody): a) Negative control of parotid gland tissue. b) positive control staining of testicular tissue. c) negative staining of tumor tissue. d) weakly positive staining of pan-MAGE. e) moderately strong expression of pan-MAGE in tumor tissue with solid growth pattern, stroma tissue is negative. f) example of strong expression of pan-MAGE in >70% of ACC tumor cells.

Figure 4

Analysis of overall survival (OS) and progression free survival (PFS) of HNACC patients in based on CTA expression status: A: OS of NY-ESO-1 positive vs. negative patients, B: PFS of NY-ESO-1 positive vs. negative patients, C: OS of pan-MAGE positive vs. negative patients, D: PFS of pan-MAGE positive vs. negative patients.

Figure 5

Analysis of overall survival (OS) of patients with head and neck adenoid cystic carcinoma (HNACC) based on CTA expression status. Patients positive for both pan-Melanoma antigen (pan-MAGE) and New York esophageal squamous cell carcinoma (NY-ESO-1) show significantly worse (p=0.047) OS than patients with negative expression status