Immunologic factors can promote the progression of oral squamous cell carcinomas (oscc). The phylogenetic highly conserved protein Galectin 3 (Gal3) contributes to cell differentiation and immune homeostasis. There is evidence that Gal3 is involved in the progression of oscc and influences the regulation of macrophage polarization. Macrophage polarization (M1 vs. M2) in solid malignancies like oscc contributes to tumor immune-escape. However, the relationship between macrophage polarization and Gal3 expression in oscc is not yet understood. The current study analyzes the association between histomorphologic parameters (T-, N-, L- Pn-status, grading) and Gal3 expression resp. the ratio between Gal3 expressing cells and CD68 positive macrophages in oscc specimens.
Preoperative diagnostic biopsies (n = 26) and tumor resection specimens (n = 34) of T1/T2 oscc patients were immunohistochemically analyzed for Gal3 and CD68 expression. The number of Gal3 expressing cells and the ratio between CD68 and Gal3 expressing cells was quantitatively assessed.
In biopsy and tumor resection specimens, the number of Gal3 positive cells as well as the Gal3/CD68 ratio were significantly (p < 0.05) higher in T2 oscc compared to T1 cases. In biopsy specimens, a significantly (p < 0.05) increased Gal3 expression and Gal3/CD68 ratio was associated with the progression marker lymph vessel infiltration (L1). Tumor resection specimens of cases with lymph node metastases (N+) had a significantly (p < 0.05) increased Gal3 expression. Additionally, a high Gal3/CD68 ratio correlated significantly (p < 0.05) with higher grading (G3) in tumor resection specimens.
High Gal3 expression in oscc is associated with tumor size (T-status) and parameters of malignancy (N-, L-status, grading). Gal3 might contribute to M2 macrophage mediated local immune tolerance. Gal3 expression shows association with prognosis in oscc and represent a potential therapeutic target.
Weber M, Buttner-Herold M, Hyckel P, Moebius P, Distel L, Ries J, Amann K, Neukam FW, Wehrhan F. Small oral squamous cell carcinomas with nodal lymphogenic metastasis show increased infiltration of M2 polarized macrophages--an immunohistochemical analysis. J Craniomaxillofac Surg. 2014;42(7):1087–94. CrossRefPubMed
Wehrhan F, Hyckel P, Guentsch A, Nkenke E, Stockmann P, Schlegel KA, Neukam FW, Amann K. Bisphosphonate-associated osteonecrosis of the jaw is linked to suppressed TGFbeta1-signaling and increased Galectin-3 expression: a histological study on biopsies. J Transl Med. 2011;9:102. CrossRefPubMedPubMedCentral
Hossaka TA, Focchi GR, Oshima CT, Ribeiro DA. Detection of galectins during malignant transformation of oral cells. Dental Res J. 2013;10(4):428–33.
AC MK, Farnworth SL, Hodkinson PS, Henderson NC, Atkinson KM, Leffler H, Nilsson UJ, Haslett C, Forbes SJ, Sethi T. Regulation of alternative macrophage activation by galectin-3. J Immunol. 2008;180(4):2650–8. CrossRef
Honjo Y, Inohara H, Akahani S, Yoshii T, Takenaka Y, Yoshida J, Hattori K, Tomiyama Y, Raz A, Kubo T. Expression of cytoplasmic galectin-3 as a prognostic marker in tongue carcinoma. Clin Cancer Res. 2000;6(12):4635–40. PubMed
Mesquita JA, Queiroz LM, Silveira EJ, Gordon-Nunez MA, Godoy GP, Nonaka CF, Alves PM. Association of immunoexpression of the galectins-3 and -7 with histopathological and clinical parameters in oral squamous cell carcinoma in young patients. Eur Arch Otorhinolaryngol. 2016;273(1):237–43. CrossRefPubMed
Balermpas P, Rodel F, Liberz R, Oppermann J, Wagenblast J, Ghanaati S, Harter PN, Mittelbronn M, Weiss C, Rodel C, et al. Head and neck cancer relapse after chemoradiotherapy correlates with CD163+ macrophages in primary tumour and CD11b+ myeloid cells in recurrences. Br J Cancer. 2014;111(8):1509–18. CrossRefPubMedPubMedCentral
Wehrhan F, Buttner-Herold M, Hyckel P, Moebius P, Preidl R, Distel L, Ries J, Amann K, Schmitt C, Neukam FW, et al. Increased malignancy of oral squamous cell carcinomas (oscc) is associated with macrophage polarization in regional lymph nodes - an immunohistochemical study. BMC Cancer. 2014;14:522. CrossRefPubMedPubMedCentral
Ruvolo PP. Galectin 3 as a guardian of the tumor microenvironment. Biochim Biophys Acta. 2016;1863(3):427-37.
- Galectin 3 expression in primary oral squamous cell carcinomas
Carol I. Geppert
Friedrich W. Neukam
- BioMed Central
Neu im Fachgebiet Onkologie
Mail Icon II