Abstract
Salivary gland malignancies of the head and neck form a heterogeneous group. Adenoid cystic carcinomas are an aggressive entity of salivary gland malignancies characterized by frequent distant metastases and poor response to radio- and chemotherapy. AF1Q is a MLL fusion partner, which can activate Wnt and STAT3 signaling. Recently, overexpression of AF1q has been identified as a poor prognosticator in patients of different malignancies. A total of 46 patients with adenoid cystic carcinoma were immunohistochemically evaluated for expression of AF1q and clinical outcome was analyzed in this context. Additionally, STAT3 and the Wnt downstream target CD44 were investigated and correlated with AF1q. AF1q was overexpressed in 52.2%. Overexpression of AF1q was associated with poorer overall survival (p = 0.03). Additionally, lymph node metastases and solid tumor parts were more frequently observed in AF1qhigh patients (p = 0.07 and 0.05, respectively). AF1q did not influence the occurrence of distant metastases. Expression of AF1q was associated with higher levels of STAT3 and CD44 (p = 0.003 and 0.006, respectively). AF1q is a novel prognostic marker for poor overall survival in adenoid cystic carcinoma patients. The deleterious effects on survival may be a result of promotion of the STAT3 and Wnt pathway.
Highlights
Malignancies originating from salivary gland tissue are rare and have a reported incidence rate of 5–10 per 1,000,000. [1]Gregor Heiduschka and Lukas Kenner contributed to this work.Pathology, University of Veterinary Medicine, Vienna, AustriaIn addition, salivary gland malignancies appear as a heterogeneous group with several different histologic subtypes
[8] the chromosomal abnormality that was detected is not observed in solid tumors, AF1q expression has been found in various other malignancies including solid tumors. [9, 10] The oncogenic potential of AF1q may be a result of its capability to activate the Wnt pathway
[11] Activation of the Wnt pathway through beta catenin is associated with decreased survival rates in patients with major and minor salivary gland malignancies. [12, 13] expression of AF1q enhances the oncogenic STAT3 signaling pathway via upregulation of PDGF-B and consecutive phosphorylation of the PDGF receptor beta
Summary
Malignancies originating from salivary gland tissue are rare and have a reported incidence rate of 5–10 per 1,000,000. [1]Gregor Heiduschka and Lukas Kenner contributed to this work.Pathology, University of Veterinary Medicine, Vienna, AustriaIn addition, salivary gland malignancies appear as a heterogeneous group with several different histologic subtypes. [3] This kind of salivary gland carcinoma is characterized by distant metastases, high rate of recurrences and perineural invasion. [7] AF1q and its cofactors TCF1, beta-catenin and LEF1 form a transcriptional complex and activate the expression of CD44, a downstream target of the Wnt pathway. [11] Activation of the Wnt pathway through beta catenin is associated with decreased survival rates in patients with major and minor salivary gland malignancies. [12, 13] expression of AF1q enhances the oncogenic STAT3 signaling pathway via upregulation of PDGF-B and consecutive phosphorylation of the PDGF receptor beta. Bu and colleagues have demonstrated that selective inhibition of STAT3 by the small molecule inhibitor S3I201 results in decreased cellular proliferation, migration and invasion of ACC cell lines. Bu and colleagues have demonstrated that selective inhibition of STAT3 by the small molecule inhibitor S3I201 results in decreased cellular proliferation, migration and invasion of ACC cell lines. [15]
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