Abstract 1072: TAM and CD44 in medullary thyroid carcinoma

Abstract

Abstract Background: Tumor-associated macrophages (TAMs) are alternatively activated or M2 macrophages that infiltrate cancer tissues. It has been suggested that TAMs exert several pro-tumor functions by releasing several growth factors and proangiogenic cytokines that favor tumor progression. In fact, TAM density has been associated with poor prognosis. Although it is well known the pro-tumor roles of TAM in several tumor types, its role in medullary thyroid cancer (MTC) is still unknown. We here evaluated the M2 macrophage marker CD163 in MTC and correlated with RET mutational status and clinical and pathological features. Because it has been suggested TAMs could interact with CD44-positive tumor cells to during tumorigenesis process, we also investigated the expression of CD44 in MTC. Patients and Methods: CD163 and CD44 expression we investigated in 78 MTC by immunohistochemistry (IHC). Because hereditary form is caused by germline mutations in the RET gene, all patients were screened for RET mutations (exons 8, 10, 11, 13-16) in the DNA isolated from blood samples. Those MTC that were negative for RET germline mutations, were also screened for somatic mutations in the RET gene (exons 10, 11 e 16). Results: Germline mutation in the RET gene were identified in 29 patients (p.G533C, p.C609Y, p.C611Y, p.C620Y, p.C634R, p.C634Y/Y791F, p.S891A and p.M918V). Approximately 49 cases are sporadic cases in which somatic RET mutations were identified in about 6 cases (p.M918T, p.C634R and p.C634Y). CD163 expression was mainly found in sporadic MTC when compared to hereditary MTC (p=0.021), suggesting that TAM may play a role in the progression of sporadic MTC. On the other hand CD44 expression was mainly found in hereditary MTC than in sporadic cases (p=0.017), particularly in patients with RET germlime mutation at codon C634. Conclusion: TAM seems to be more important for sporadic MTC tumorigenesis when compared to hereditary MTC. On the other hand, CD44 expression correlated with hereditary MTC, particularly in patients with mutation at codon C634. Citation Format: MARTA MIYAZAWA, MARIA JOSE C. P. SANTOS, LARISSA V. BIM, ERIKA S. L. ORTI-RADUAN, FLÁVIA O. F. VALENTE, ADAUTO F. NUNES, ROSANA DELCELO, RUI M. B. MACIEL, JANETE M. CERUTTI. TAM and CD44 in medullary thyroid carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1072. doi:10.1158/1538-7445.AM2014-1072