Galectin-3 Expression in High-Risk HPV-Positive and Negative Head & Neck Squamous Cell Carcinomas and Regional Lymph Node Metastases

Abstract

Despite higher stages at presentation, patients with high-risk (HR) HPV-related (HPV+) head and neck squamous cell carcinomas (HNSCCs) have better survival rates compared to those with non-HPV-related (HPV-) disease. However, significant comorbidity and the number of patients who suffer failed treatment, recurrent disease, late metastasis, and death are increasing along with the incidence of HPV+ HNSCC. A cytotoxic T-cell-dependent immune response is required to clear these antigenic cancers. This provides a unique opportunity to employ immune modulators in therapy. Galectin-3 (Gal-3) is a lectin and glycoprotein involved in numerous immunosuppressive functions. Inhibitors are currently under clinical investigation for various diseases. Gal-3 expression was evaluated in HR-HPV+ and HPV- HNSCCs and regional lymph node metastases by tissue microarray. HR-HPV+ cases were more likely to be Gal-3-positive (Gal+) [50% (14/28)] than HPV- cases [18% (9/50), p = 0.004]. No difference in the number of Gal+ cases was identified between primary [30% (16/53)] and metastatic [28% (7/25)] cancers (p = 1); 53% (9/17) of primary HPV+ cancers were Gal+ and 45% (5/11) of metastatic HPV+ cancers were Gal+ (p = 1). Nineteen percent (7/36) of primary HPV- cancers were Gal+ and 14% (2/14) of metastatic HPV- cancers were Gal+ (p = 1). Gal-3 positivity was observed in a subset of HNSCC, suggesting a potential role for therapeutic inhibition in this tumor type. The significantly higher rates of expression seen in HR-HPV+ versus HPV- HNSCC suggest particular promise in the setting of HPV infection. The relatively consistent Gal-3 expression rates observed between metastatic and primary tumors argues against progressive Gal-3 expression in metastasis.

Keywords: Galectin 3; Head and neck cancer; Human papilloma virus; Metastasis; Oropharyngeal cancer; Squamous cell carcinoma.

Conflict of interest statement

No conflict of interest to disclose.

Figures

Fig. 1

High-risk HPV status by RNA in situ hybridization.a HPV-positive squamous cell carcinoma (H&E, × 200 total magnification). b HR-HPV RNA ISH with nuclear and cytoplasmic dot-like positivity (× 200 total magnification). c HPV-negative squamous cell carcinoma (H&E, × 200 total magnification). d Negative HR-HPV RNA ISH (× 200 total magnification)

Fig. 2

Gal-3 expression by immunohistochemistry in primary HNSCC. a An example of a Gal-3 positive primary oral SCC (H&E, × 400 total magnification) and b Gal-3 IHC demonstrating cytoplasmic and some nuclear staining in a majority of tumor cells (× 400 total magnification). c A contrasting example of a Gal-3 negative primary oral SCC (H&E, × 400 total magnification) and D) Gal-3 IHC demonstrating a complete lack of staining (× 400 total magnification)

Fig. 3

Gal-3 expression by immunohistochemistry in metastatic HNSCC. a An example of a Gal-3 positive HNSCC lymph node metastasis (H&E, × 400 total magnification) and b Gal-3 IHC demonstrating staining in a majority of tumor cells (× 400 total magnification). c In contrast, a Gal-3 negative HNSCC lymph node metastasis (H&E, × 400 total magnification) and d Gal-3 IHC demonstrating a complete lack of staining (× 400 total magnification)