Role of apoptotic, autophagic and senescence pathways in minor salivary gland adenoid cystic carcinoma
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(2019) 14:14
RESEARCH
Open Access
Role of apoptotic, autophagic and senescence pathways in minor salivary gland adenoid cystic carcinoma João Augusto Vianna Goulart-Filho, Victor Angelo Martins Montalli, Fabrício Passador-Santos, Ney Soares de Araújo and Vera Cavalcanti de Araújo*
Abstract Background: Adenoid cystic carcinoma (ACC) is a salivary gland malignancy with poor long-term survival, which warrants studies aimed at clarifying the pathogenesis of this disease in order to widen the scope of therapeutic options currently available. Alterations in regulatory mechanisms relating to vascular support, cell death and autophagy are important pathways for tumor growth in cancer. Thus, the present study aimed to access vascular supply, apoptosis, autophagy and cell senescence in ACC of minor salivary glands. Methods: We analyzed 25 cases of minor salivary gland ACC by immunohistochemistry using anti-CD34, antiCD105, anti-D2–40, anti-Bax, anti-Bcl-2, anti-Beclin-1, anti-LC3B, anti-p21 and anti-p16. Results: Microvessel density was low and based on anti-CD34, anti-CD105 and anti-D2–40 immunostaining. There was positivity for anti-CD34, anti-Bcl-2, anti-Beclin, anti-LC3B and anti-p21 and a positive correlation between Bcl-2 and Beclin (p = 0.014). Conclusions: Our results showed that ACC does not depend on neo-angiogenesis and is probably associated to anti-apoptotic, autophagic and anti-senescence events. Keywords: Adenoid cystic carcinoma, Angiogenesis, Apoptosis, Autophagy, Senescence
Background Adenoid cystic carcinoma (ACC) represents 1% of all head and neck cancers and 10–15% of all salivary gland tumours and is characterized by indolent growth, perineural invasion and multiple local recurrences. In contrast to rare regional lymphatic metastasis, hematogenous metastases occur particularly to the lungs, bones and liver [1– 3]. Surgical resection followed by radiotherapy is the treatment of choice, but the relentless nature of tumour growth and high potential for local recurrences usually makes treatment difficult, mutilating and non-responsive to chemotherapy, contributing to a poor prognosis and making many authors consider ACC as a “clinically high-grade” neoplasm [4–6]. Microscopically, ACC is composed by luminal and myoepithelial cells and may present three distinct patterns: cribriform, tubular and * Correspondence: [email protected] Department of Oral Pathology, São Leopoldo Mandic Research Institute, Rua José Rocha Junqueira, 13, CEP, Campinas, SP 13045-610, Brazil
solid, the latter showing the worst prognosis and poorest survival [3, 6, 7]. This study aims to evaluate microvascularization (CD34 and CD105), apoptosis (Bcl-2 and Bax), autophagy (Beclin and LC3B) and senescence (p21 and p16) in minor salivary gland ACC.
Methods Twenty-five formalin-fixed paraffin-embedded samples of ACC derived from minor salivary glands were obtained from the archives of the Oral Pathology Laboratory of São Leopoldo Mandic Institute and Research Center. All cases underwent immunohistochemical staining for the following an
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