ConclusõesConclusões
Conclusões
7. CONCLUSÕES
Diante dos resultados obtidos no presente estudo, pode-se concluir que:
1. O AP, CME e CAC exibiram maior expressão de OCT4 e CD44 do que o parênquima glandular salivar normal.
2. Dentre as células do parênquima tumoral dos casos avaliados, foi evidenciado para o OCT4 que as células luminais e não-luminais foram imunomarcadas nos casos de APs e CACs. Já a imunoexpressão do CD44 foi evidenciada principalmente nas células não- luminais destas lesões. Nos CMEs para ambos marcadores, verificou-se imunorreatividade nas células epidermóides e intermediárias e ausência de marcação nas células mucosas, sugerindo que estas células podem apresentar maior grau de diferenciação e um fenótipo menos agressivo, não exibindo comportamento de células- tronco tumorais, e assim, parecem não estar envolvidas no comportamento agressivo dos CMEs.
3. Os subtipos do AP, as gradações do CME e os padrões histopatológicos do CAC não influenciaram as expressões de OCT4 e CD44.
4. As neoplasias localizadas nas GSMA exibiram maior imunomarcação tanto para OCT4 quanto para CD44 quando comparada com as lesões das GSME. A diferença de expressão pode ser resultante da variação das características histológicas entre as glândulas salivares e/ou características inerentes ao desenvolvimento embriológico através da relação epitélio-mesenquimal.
5. Na amostra total e no grupo das GSME, o CME e o CAC exibiram maior imunomarcação para OCT4 do que o AP, sendo possível sugerir que as células-tronco tumorais estariam relacionadas ao comportamento biológico das neoplasias de glândula salivar.
6. Foi observada uma correlação positiva entre a expressão de OCT4 e CD44 para a amostra total. Assim, estes biomarcadores de células-tronco tumorais mostraram que estão relacionados com a tumorigênese em TGS.
Referências
Referências
Referências
Referências
8. REFERÊNCIAS
ABRAHÃO, A. C. et al. Clinicopathological characteristics of tumours of the intraoral minor salivary glands in 170 Brazilian patients. British Journal of Oral and Maxillofacial Surgery. http://dx.doi.org/10.1016/j.bjoms.2015.10.035, 2015.
ADAMS, A. et al. Salivary gland cancer stem cells. Oral Oncology. v.49, p.845–853, 2013. ADAMS, A. et al. ALDH/CD44 identifies uniquely tumorigenic cancer stem cells in salivary gland mucoepidermoid carcinomas. Oncotarget. v.6, n.29, p.26633-26650, 2015.
AL-HAJJ, M. et al. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA, v.100, p.3983–3988, 2003.
ALMANAA, T. N.; GEUSZ, M. E.; JAMASBI, R. J. A new method for identifying stem-like cells in esophageal cancer cell lines. J Cancer. v.4, n.7, p.536–48, 2013.
ASP, J. et al. CHCHD7-PLAG1 and TCEA1-PLAG1 Gene Fusions Resulting from Cryptic, Intrachromosomal 8q Rearrangements in Pleomorphic Salivary Gland Adenomas. Genes, Chromosomes & Cancer. v.45, p.820-828, 2006.
BACCELLI, I.; TRUMPP, A. The evolving concept of cancer and metastasis stem cells. J Cell Biol. v.198, p.281-93, 2012.
BAI et al. Salivary mucoepidermoid carcinoma: a multi-institutional review of 76 patients. Head Neck Pathol. v.7, n.2, p.105-12, 2013.
BARNES, L. et al. World Health Organization Classification of Tumours. Pathology and Genetics of Head and Neck Tumours. Lyon: IARC Press; p. 166-75, 2005.
BARROSO, K. M. A. Expressão de vegf-c, vegf-d, mensuração da densidade linfática e da proliferação endotelial linfática em neoplasias de glândula salivar. 2014. 136f. Tese (Doutorado em Patologia Oral). Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte. 2014.
BASAKRAN, N. S. CD44 as a potential diagnostic tumor marker. Saudi Med J. v.36 n.3, p.273-279, doi: 10.15537/smj.2015.3.9622, 2015.
BECK, B.; BLANPAIN, C. Unravelling cancer stem cell potential. Nat Rev Cancer. v.13, p.727-738, 2013.
BEN-PORATH, I. et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. v.40, p.499-507, 2008.
BIANCHI, B. et al. Adenoid cystic carcinoma of intraoral minor salivary gland. Oral Oncol., v. 44, n. 11, p. 1026-1031, 2008.
BHAIJEE, F. et al. Cancer stem cells in head and neck squamous cell carcinoma: a review of current knowledge and future applications. Head Neck, v.34, n.6, p.894-9, 2012.
BLUTEAU, G. et al. Stem cells for tooth engineering. Eur Cell Mater. v.16, p. 1-9, 2008. BOKO, E. et al. Tumours of the accessory salivary glands. Epidemiological and anatomopathological aspects. Rev Laryngol Othol Rhinol, p. 233-37, 2004.
BONNET, D.; DICK, J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. v.3, p.730–737, 1997.
BOROVSKI, T. et al. Cancer stem cell niche: the place to be. Cancer Res. v.71, n.3, p.634-9, 2011.
BOYER, L.A. et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. v.122, p.947-956, 2005.
CAMPBELL, L. L. et al. Breast tumor heterogeneity: cancer stem cells or clonal evolution? Cell Cycle. v.6 p.2332–2338, 2007.
CHEN, Z. G. The cancer stem cell concept in progression of head and neck cancer. Journal of Oncology, v.2009, ID 894064, 2009.
CHEUK, W.; CHAN, J. K. Advances in salivary gland pathology. Histopathology. v. 51, n.1, p. 1-20, 2007.
CHIOU, S. H. et al. Positive Correlations of Oct-4 and Nanog in Oral Cancer Stem-Like Cells and High-Grade Oral Squamous Cell Carcinoma. Clin Cancer Res. v.14, n.13, p.4085–4095, 2008.
CLEVERS, H. The cancer stem cell: premises, promises and challenges. Nat Med.v.17, p.313-319, 2011.
COCA-PELAZ, A. et al. Adenoid cystic carcinoma of the head and neck – An update. Oral Oncology, v. 51, p.652–661, 2015.
COLLINS, A.T. al. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. v.65, p.10946–10951, 2005.
COWAN, C.A. et al. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science. v.309, n.5739, p.1369-73, 2005.
DAI, W. et al. High Expression of SOX2 Is Associated with Poor Prognosis in Patients with Salivary Gland Adenoid Cystic Carcinoma. Int. J. Mol. Sci. v.15, p.8393-8406, 2014.
DARINI, C.Y. et al. Self renewal gene tracking to identify tumour-initiating cells associated with metastatic potential. Oncogene. v.31, p.2438-49, 2012.
Da SILVEIRA, E. J. D. et al. Myoepithelioma of minor salivary gland – an immunohistochemical analysis of four cases. Rev. Bras. Otorrinolaringol., v.72, n.4, p.528- 532, 2006.
De OLIVEIRA, L. C. Estudo imuno-histoquímico da expressão de Glut-1 e mensuração do índice angiogênico (CD34) em adenomas pleomórficos, carcinomas adenóides císticos e carcinomas mucoepidermóides de glândulas salivares. 2012. 109f. Dissertação (Mestrado em Patologia Oral). Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte. 2012.
DEBIEC-RYCHTER, M. et al. Histologic Localization of PLAG1 (Pleomorphic adenoma gene 1) in pleomorphic adenoma of the salivary gland: cytogenetic evidence of common origin of phenotypically diverse cells. Lab Invest. v.81, p.1289-1297, 2001.
DECLERCQ, J. et al. Upregulation of Igf and Wnt signalling associated genes in pleomorphic adenomas of salivary glands in PLAG1 transgenic mice. Int. J. Oncol. v. 32, p. 1041-1047, 2008.
DWIVEDI, N. et al. Histogenesis of salivary gland neoplasms. Indian J Cancer, v.50, n.4, p.361-366, 2013.
EBBEN J. D. The cancer stem cell paradigma: a new understanding of tumor development and treatment. Expert Opin Ther Targets. v.14, p.621-32, 2010.
ELLEDGE, R. Current concepts in research related to oncogenes implicated in salivary gland tumourgenesis: a review of the literature. Oral Dis., v. 15, p. 249-254, 2009.
ELLIS, G. L.; AUCLAIR, P. L. Tumors of the salivary glands. AFIP Atlas of Tumor Pathology. 4th series, fascicle 9. Silver Spring MD: ARP Press, 2008.
EL-NAGGAR, H., HUVOS, A. G. Adenoid cystic carcinoma. In Barnes, L. et al. (Eds) Pathology and genetics of head and neck tumours. Lyon: IARC Press, 2005. p.221-222. ENAMORADO, I. et al. Correlation of histopathological variants, cellular DNA content, and clinical outcome in adenoid cystic carcinoma of the salivary glands. Otolaryngol Head Neck Surg. v.131, p.646-650, 2004.
ENESCU, A. S. et al. Histopathological study of pleomorphic adenoma of salivary glands. Rom J Morphol Embryol. v.55 (3 Suppl), p.1149–1153, 2014.
ERDEM, M. A. et al. Pleomorphic adenoma of the palate. J Craniofac Surg, v. 22, n. 3, p. 1131-4, 2011.
EVESON, J. W. et al. Pleomorphic adenoma.In: Barnes, L. et al. (Eds) Pathology and genetics of head and neck tumours. Lyon: IARC Press, 2005. p. 254-258.
FONSECA, I. et al. Expression of CD44 isoforms in normal salivary gland tissue: an immunohistochemical and ultrastructural study. Histochem Cell Biol, v.114, p.483–8, 2000. FREITAS, V.S. Estudo da expressão imuno-histoquímica das MMPs -2, -7, -9 e -26 e dos TIMPS -1 E -2 em adenomas pleomórficos e carcinomas adenóides císticos de glândulas salivares menores. 2011. 156f Tese (Doutorado em Patologia Oral), Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte. 2011.
FU, T. Y. et al. Association of OCT4, SOX2, and NANOG expression with oral squamous cell carcinoma progression. J Oral Pathol Med. doi: 10.1111/jop.12335, 2015.
FUCHS, E.; TUMBAR, T.; GUASCH, C. Socializing with the neighbors: stem cells and their niche. Cell. v. 116, n.6, p.769-78, 2004.
FUJITA, S.; IKEDA, T. Cancer stem-like cells in adenoid cystic carcinoma of salivary glands: relationship with morphogenesis of histological variants. J Oral Pathol Med v.41, n.3, p.207–13, 2012.
GAGE, F. H. Mammalian neural stem cells. Science, Washington, DC, v.287, p.1433-1438, 2000.
GE, N. et al. Prognostic significance of Oct4 and Sox2 expression in hypopharyngeal squamous cell carcinoma. Journal of Translational Medicine, v.8, n.94, p.1-7, 2010.
GLEBER-NETTO, F. O. et al. Angiogenesis and lymphangiogenesis in mucoepidermoid carcinoma of minor salivary glands. J Oral Pathol Med. V.41, n.8, p.603-609, 2012.
GOODE, R. K.; EL-NAGGAR, A. K. Mucoepidermoid carcinoma. In Barnes, L. et al. (Eds).World Health Organization classification of tumours: head and neck tumours. Lyon: IARC Press, 2005.
GOULART, M. C. V. et al. Pleomorphic adenoma with extensive squamous metaplasia and keratin cyst formations in minor salivary gland: a case report. J Appl Oral Sci, v. 19, n. 2, p. 182-8, 2011.
GURBUZ, Y. et al. Immunophenotypical profiles of salivary gland tumours: a new evidence for their histogenetic origin. Pathologica, v.98, p.147–152, 2006.
HABU, N. et al. Expression of Oct3/4 and Nanog in the head and neck squamous carcinoma cells and its clinical implications for delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma. BMC Cancer, v.15, n.730, DOI 10.1186/s12885-015-1732-9, 2015.
HASSIOTOU, F. et al. Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary gland. Frontiers in Oncology. v.3, n.79, p.1-15, 2013.
HSU, Y.C.; FUCHS, E. A family business: stem cell progeny join the niche to regulate homeostasis. Nat Rev Mol Cell Biol.v.13, p.103-114, 2012.
HUANG, C.F. et al. Correlation of ALDH1, CD44, OCT4 and SOX2 in tongue squamous cell carcinoma and their association with disease progression and prognosis. J Oral Pathol Med. v.43,p.492–498, 2014.
IANEZ, R.C. et al. CD24 and CD44 in salivary gland pleomorphic adenoma and in human salivary gland morphogenesis: differential markers of glandular structure or stem cell indicators? Oncol Res. v.15, n.12, p.589-600, 2013.
ISLAM, F. et al. Translational potential of cancer stem cells: A review of the detection of cancer stem cells and their roles in cancer recurrence and cancer treatment. Experimental Cell Research. v.335, p.135–147, 2015a.
ISLAM, F. et al. Cancer stem cell: Fundamental experimental pathological concepts and updates. Experimental and Molecular Pathology. v. 98, p.184–191, 2015b.
ITO, F. A. et al. Salivary gland tumors in a Brazilian population: a retrospective study of 496 cases. Int. J. Oral Mxillofac. Surg. v. 34, p.533-536, 2005.
ITO, F. A. et al. Histopathological findings of pleomorphic adenomas of the salivary glands. Med. Oral Patol.Oral Cir. Bucal, v. 14, n. 2, p. 57-61, 2009.
JAENISCH, R.; YOUNG, R. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell. v.132, p.567-582, 2008.
JONES, A.V. et al. The range and demographics of salivary gland tumours diagnosed in a UK population. Oral Oncol., v.44, p.407-17, 2008.
KANDASAMY, J. et al. Heterogeneity of PLAG1 gene rearrangements in pleomorphic adenoma. Cancer Genet Cytogenet. v.177, p.1-5, 2007.
KAS, K. et al. Transcriptional activation capacity of the novel PLAG family of zinc finger proteins. J Biol Chem. v.273, p.23026-23032, 1998.
KIM, J. W. et al. Carcinoma ex Pleomorphic Adenoma of the Salivary Glands: Distinct Clinicopathologic Features and Immunoprofiles Between Subgroups According to Cellular Differentiation. J Korean Med Sci.,v. 26, n. 10, p. 1277-85, 2011.
KLEIN, A.M.; SIMONS, B.D. Universal patterns of stem cell fate in cycling adult tissues. Development. v.138, p.3103-3111, 2011.
KLONISCH, T. et al. Cancer stem cell markers in common cancers therapeutic implications. Trends Mol Med. v.14, p.450-460, 2008.
KOBAYASHI, N. C. C.; NORONHA, S. M. R. Cancer stem cells: a new approach to tumor development. Rev Assoc Med Bras. v. 61, n.1, p.86-93, 2015.
KOLYA, C. L.; CASTANHO, F. L. Células-tronco e Odontologia. ConScientiae Saúde. v. 6, n.1, p.165-71, 2007.
KOMIYA, T. et al. Sustained expression of Mect1-Maml2 is essential for tumor cell growth in salivary gland cancers carrying the t(11;19) translocation. Oncogene. v.25, p.6128-6132, 2006.
KOKKO, L. L. et al. Significance of site-specific prognosis of cancer stem cell marker CD44 in head and neck squamous-cell carcinoma. Oral Oncology, v. 47, p.510–516, 2011.
KOO, B. S. et al. Oct4 is a critical regulator of stemness in head and neck squamous carcinoma cells. Oncogene. doi:10.1038/onc.2014.174, 2014.
KRISHNAMURTHY, S.; NÖR, J. E. Head and neck cancer stem cells. J Dent Res. v.91, n.4, p.334-40, 2012.
KRIVTSOV, A.V. et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature. v.442, p.818–822, 2006.
KUHN, N. Z.; TUAN, R. S. Regulation of stemness and stem cell niche of mesenchymal stem cells: implications in tumorigenesis and metastasis. J Cell Physiol. v.222, n.2, p.268-77, 2010.
LEE, H. E. et al. An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer. Br. J. Cancer. v.104, p.1730–1738, 2011.
LEINUNG, M. et al. Expression of ALDH1A1and CD44 in primary head and neck squamous cell carcinoma and their value for carcinogenesis tumor progression and cancer stem cell identification. Oncology Letters. v.10, p.2289-2294, 2015.
LEONIDA, A. et al. Effects of low-level laser irradiation on proliferation and osteoblastic differentiation of human mesenchymal stem cells seeded on a three-dimensional biomatrix: in vitro pilot study. Lasers Med Sci. v.28, p.125-132, 2013.
LI, C. et al. Identification of pancreatic cancer stem cells. Cancer Res. v.67, p.1030–1037, 2007.
LI, H. et al. The expression of MACC1 and its role in the proliferation and apoptosis of salivary adenoid cystic carcinoma. J Oral Pathol Med, v.44, p.810–817, 2015.
LIU, S. et al. Prognostic factors in primary salivary gland mucoepidermoid carcinoma: an analysis of 376 cases in an Eastern Chinese population. Int J Oral Maxillofac Surg. v.43, n.6, p.667-73, 2014.
LO, B.; PARHAM, L. Ethical Issues in Stem Cell Research. Endocr Rev. v.30, n.3, p.204- 213, 2009.
MACK, B.; GIRES, O. CD44s and CD44v6 Expression in Head and Neck Epithelia. PLoS ONE, v. 3, n.10, e3360, 2008.
MAJOR, A. G.; PITTY, L.P.; FARAH, C.S. Cancer Stem Cell Markers in Head and Neck Squamous Cell Carcinoma. Stem Cells International. Article ID 319489,13pages
http://dx.doi.org/10.1155/2013/319489, 2013.
MANI, S. A. et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, v.133, p.704–715, 2008.
MĂRGĂRITESCU, C. et al. Tumoral stroma of salivary pleomorphic adenoma – histopathological, histochemical and immunohistochemical study. Rom J. Morphol. Embryol. v.46, p.211-23, 2005.
MARTÍNEZ-RODRÍGUEZ, N. et al. Epidemiology and treatment of adenoid cystic carcinoma of the minor salivary glands: A meta-analytic study. Med Oral Patol Oral Cir Bucal - AHEAD OF PRINT, 2011.
MARTINS, C. et al. PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma expleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry. Journal Mod Pathol. v.18, p.1048-1055, 2005.
MARUSE, Y. et al. A case of mucoepidermoid carcinoma of the sublingual gland accompanied with extensive dystrophic calcification and intratumoral bone formation. Head Neck. doi: 10.1002/hed.24036, 2015.
MEYERS, M. et al. Head and neck adenoid cystic carcinoma: A prospective multicenter REFCOR study of 95 cases. European Annals of Otorhinolaryngology, Head and Neck diseases. http://dx.doi.org/10.1016/j.anorl.2015.09.009, 2015.
MIN, R. et al. Salivary gland adenoid cystic carcinoma with cervical lymph node metastasis: a preliminary study of 62 cases. Int. J. Oral Maxillofac. Surg. v. 41, p.952–957, 2012.
MOGHBELI, M. et al. Cancer stem cell detection and isolation. Med Oncol. v.31, p.69-75, 2014.
MOSKALUK, C.A. Adenoid cystic carcinoma: clinical and molecular features. Head Neck Pathol. v.7, n.1, p.17-22, 2013.
NANDURI, L.S. et al. Regeneration of irradiated salivary glands with stem cell marker expressing cells. Radiother Oncol. v.99, n.3, p.367-72, 2011.
NEVILLE, B. W. et al. Patologia Oral e Maxilofacial. 3 ed. Rio de Janeiro: Elsevier, 2009. 972 p.
NIE, D. Cancer stem cell and niche. Front Biosci (Schol Ed), v.2, p.184–193, 2010.
NIKOLIC, N. et al. High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors. Archives of Oral Biology. v.60, p.1662–1666, 2015.
NÓBREGA, M. Q. R. et al. Neoplasias de glândulas salivares menores: estudo retrospectivo de 83 casos. RGO - Rev Gaúcha Odontol., v. 58, n. 3, p. 357-362, 2010.
NOURI, F.S.; BANERJEE, D.; HATEFI, A. Practical Issues with the Use of Stem Cells for Cancer Gene Therapy. Stem Cell Rev and Rep. v.11, p.688–698, 2015.
O'CONNOR, M. L. et al. Cancer stem cells: a contentious hypothesis now moving forward. Cancer Lett. v.344, p.180–187, 2014.
OGAKI, S. et al. Wnt and Notch signals guide embryonic stem cell differentiation into the intestinal lineages. Stem Cells. v.31, p.1086-1096, 2013.
OKAMOTO, A. et al. Expansion and characterization of cancer stem-like cells in squamous cell carcinoma of the head and neck. Oral Oncol, v.45, n.7, p.633-9, 2009.
OKUDA, H. et al. Hyaluronan synthase HAS2 promotes tumor progression in bone by stimulating the interaction of breast cancer stem-like cells with macrophages and stromal cells. Cancer Res, v.72, p.537-547, 2012.
OLIVEIRA, F. A. et al. Salivary Gland Tumor: A Review of 599 Cases in a Brazilian Population. Head and Neck Pathol., doi: 10.1007/s12105-009-0139-9, p.271–275, 2009. PAPADOGEORGAKIS, N. et al. Multinodular neck recurrence of parotid gland pleomorphic adenoma: a case report. Oral and Maxillofacial Surgery, 2011.
PAPAGERAKIS, S. et al. Oral epithelial stem cells – implications in normal development and cancer metastasis. Exp Cell Res v.325, n.2, p.111–129. doi:10.1016/j.yexcr.2014.04.021, 2014.
PERSSON, F. et al. High-resolution array CGH analysis of salivary gland tumors reveals fusion and amplification of the FGFR1 and PLAG1 genes in ring chromosomes. Oncogene. v.27, p.3072-3080, 2008.
PIRES, F. R. et al. Differences on clinicopathological profile from intraoral minor salivary gland tumors around the world. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. v.105, n.2, p.136-138, 2008.
PRINCE, M. E. et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA, 104(3):973– 8, 2007.
PRUD’HOMME, G. J. Cancer Stem Cells and Novel Targets for Antitumor Strategies. Current Pharmaceutical Design, v.18, p.2838-2849, 2012.
QIAO, B. et al. The expression profile of Oct4 and Sox2 in the carcinogenesis of oral mucosa. Int J Clin Exp Pathol, v.7, n.1, p.28-37, 2014.
QURESHI, S. S. et al. Hepatic resection for metastasis from adenoid cystic carcinoma of parotid gland.Indian J Gastroenterol, p. 29-30, 2005.
RAO, P. H. et al. Deletion of 1p32-p36 is the most frequent genetic change and poor prognostic marker in adenoid cystic carcinoma of the salivary glands. Clin Cancer Res. v.14, p.5181-5187, 2008.
RAVINDRAN, G. et al. Association of differential b-catenin expression with Oct-4 and Nanog in oral squamous cell carcinoma and their correlation with clinicopathological factors and prognosis. Head and Neck—DOI 10.1002/ HED, 2015.
REGEZI, J. A.; SCIUBBA, J. J.; JORDAN, R. C. K. Patologia bucal: Correlações clínicopatológicas.5ed. Rio de Janeiro: Elsevier, 2008. 417p.
ROBEY, P. G. Stem cells near the century mark. J. Clin. Invest., v.105, n.11, p.1489-1491, 2000.
RUTHERFORD, S. et al. Mapping of candidate tumor suppressor genes on chromosome 12 in adenoid cystic carcinoma. Laboratory Investigation. v.85, p.1076-1085, 2005.
RYCAJ, K.; TANG, D.G. Cancer stem cells and radioresistance. Int. J. Radiat. Biol. v.90 p.615–62, 2014.
SAHOO, N.K.; RANGAN, M.N.; GADAD, R.D. Pleomorphic adenoma palate: major tumor in a minor gland. Ann Maxillofac Surg., v.3, n.2, p.195-197, 2013.
SAITO, S. et al. Possible linkages between the inner and outer cellular states of human induced pluripotent stem cells. BMC Syst Biol. v.5, (Suppl 1), 2011.
SAITO, M. T. et al. Tooth-derived stem cells: Update and perspectives. World J Stem Cells. v.7, n.2, p. 399-407, 2015.
SARRAJ, Y. A. et al. Characteristics of salivary gland tumours in the United Arab Emirates. ecancer medicalscience, v. 9, n. 583, 2015.
SATPUTE, P. S. et al. Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review. Asian Pac J Cancer Prev. v.14, n.10, p.5579-5587, 2013.
SAWANT, S. et al. Prognostic role of Oct4, CD44 and c-Myc in radio–chemo-resistant oral cancer patients and their tumourigenic potential in immunodeficient mice. Clin Oral Invest, DOI 10.1007/s00784-015-1476-6, 2015.
SAYED, S. I. et al. Implications of understanding cancer stem cell biology in head and neck squamous cell cancer. Oral Oncol. v.47, n.4, p.237-43, 2011.
SCADDEN, D. T. The stem cell niche as in entity of action. Nature. v. 441, n.7097, p.1075- 9, 2006.
SCHWARZ, S. et al. Morphological heterogeneity of oral salivary gland carcinomas: A clinicopathologic study of 41 cases with long term follow-up emphasizing the overlapping spectrum of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma. Int J Clin Exp Pathol., v. 4, n. 4, p. 336-348, 2011.
SEIFERT, G. et al. A pathological classification of pleomorphic adenoma of the salivary glands. HNO. v. 24, n.12, p.415-426, 1976.
SELL, S. On the stem cell origin of cancer. Am J Pathol. v.176, p.2584-2594, 2010.
SERAKINCI, N.; KEITH, W. N. Therapeutic potential of adult stem cells. Eur J Cancer. v.42, n.9, p.1243-6, 2006.
SHIPITSIN, M. et al. Molecular definition of breast tumor heterogeneity. Cancer Cell, v.11, p.259–273, 2007.
SHISHEGAR, M. et al. Salivary Gland Tumors in Maxillofacial Region: A Retrospective Study of 130 Cases in a Southern Iranian Population. Pathology Research International. DOI: 10.4061/2011/934350, 2011.
SINHA, N. et al. Relevance of cancer initiating/stem cells in carcinogenesis and therapy resistance in oral cancer. Oral Oncology. v.49, p.854–862, 2013.
SLACK, J.M. Stem cells in epithelial tissues. Science Washington, v.287, n.5457, p.1431- 1433, 2000.
SMALLEY, M.; ASHWORTH, A. Stem cells and breast cancer: a field in transit. Nat. Rev. Cancer. v.3, p.832–844, 2003.
SOARES, D. M. et al. Effects of laser therapy on the proliferation of human periodontal ligament stem cells. Lasers Med Sci. DOI 10.1007/s10103-013-1436-9, 2013.
SOAVE, D.F. et al. CD44/CD24 immunophenotypes on clinicopathologic features of salivary glands malignant neoplasms. Diagn Pathol. v.8, n.29. doi: 10.1186/1746-1596-8-29, 2013. SOONG, P.L. et al Cardiac differentiation of human embryonic stem cells and their assembly into engineered heart muscle. Curr Protoc Cell Biol. Chapter 23, Unit 23.8. 2012.
SOUZA, V.F. et al. Células-tronco: uma breve revisão. R. Ci. méd. biol.,v.2, n.2, p. 251-256, 2003.
SPEIGHT, P. M. Update on diagnostic difficulties in lesions of the minor salivary glands. Head Neck Pathol., v.1, p.55-60, 2007.
STENNERT, E. et al. Recurrent pleomorphic adenoma of the parotid gland: A prospective histopathological and immunohistochemical study. Laryngoscope, v. 114, p. 158-163, 2004. STEVENS, K. R. Células-tronco, o que são? Laboratório Nacional de Células-Tronco Embrionárias - Rio de Janeiro. Disponível em: http://www.lance-ufrj.org/ceacutelulas- tronco.html, 2015.
SUN, S.; WANG, Z. ALDH high adenoid cystic carcinoma cells display cancer stem cell properties and are responsible for mediating metastasis. Biochem Biophys Res Commun. v.396, n.4, p.843–8, 2010.
SUNG, B. et al. Regulation of OCT4 gene expression by liver receptor homolog-1 in human embryonic carcinoma cells. Biochemical and Biophysical Research Communications. v.427, p.315–320, 2012.
SZAFAROWSKI, T; SZCZEPANSK, M. J. Cancer stem cells in head and neck