ABSTRACT
O carcinoma epidermóide de cabeça e pescoço se origina do epitélio estratificado escamoso através do acúmulo de alterações genéticas, devido principalmente ao consumo de álcool e tabaco. Em cabeça e pescoço, o carcinoma epidermóide acomete a cavidade nasal e seios paranasais, cavidade oral, orofaringe, hipofaringe e laringe. Apesar dos esforços para o aprimoramento dos métodos de diagnóstico e tratamento, o carcinoma epidermóide de cabeça e pescoço ainda é uma doença que apresenta alguns obstáculos no seu manejo, já que indivíduos com tumores clinica e patologicamente semelhantes, que recebem o mesmo tratamento, apresentam respostas bastante heterogêneas... Incluindo amostras de CE de esôfago, pulmão e colo de útero na análise de expressão gênica global, os dados sugerem a existência de duas classes moleculares de amostras de CECP, que apresentam expressão diferencial de genes e alteração em módulos funcionais relacionados à agressividade e progressão tumoral, e não à topografia... O conjunto de vias e módulos funcionais alterados nas diversas comparações indicam que os tumores de perfil agressivo apresentam mudanças na expressão de genes relacionados à comunicação entre microambiente, MEC e a célula tumoral. Isso pode estimular vias de sinalização que promovem a progressão tumoral através da inibição de apoptose...
Head and neck squamous cell carcinomas (HNSCC) arise from the squamous epithelium cells as result of multiple genetic alterations, mainly due to alcohol e tobacco consumption. HNSCC affects the nasal cavity and paranasal sinus, oral cavity, oropharynx, hipopharynx and larynx. Despite efforts for the improvement in diagnosis and treatment, the management of head and neck cancer is still difficult, since similar patients, affected by tumors with similar clinicopathological parameters and undergoing the same treatment, show significant heterogeneity in their outcome. Since these tumor share same histological origin, gene expression analysis of tumor from different subsites provides a better understanding of the biologic features of the disease, leading to new approaches for the classification of HNSCC. In addition, analysis of gene expression alterations related to tumor behavior may allow the identification of changes associated with tumor progression. Considering the set of genes represented in the platform, analysis of HNSCC from different subsites shows that either global gene expression or single gene expression is not strongly influenced by tumor site. When global gene expression of squamous cell carcinoma of the head and neck, esophagus, lung and cervix was assessed, two molecular types of HNSCC samples were highlighted, which are classificated according to the differential expression of genes and activation of modules associated with aggressiveness and tumor progression, and not associated with tumor subsite. Regarding HNSCC behavior, alterations in pathways and functional modules indicate that negative lymph node HNSCC samples (N0) present inactivation of modules with AKT1, AREG, CCL20, EGFR, IL1B, INHBA, and SPHK1. This alteration may not allow the survival of tumor cells within lymph nodes. Comparing "advanced" (T3-4N+) and "early" (T1-2 N0), the last ones show inactivation of MMP9. According to the literature, its blockade inhibits in vivo tumor progression (KATORI et al. 2002; YAMASHITA et al. 2003). Samples from N+ patients, treated with adjuvant radiotherapy and presenting recurrent or metastatic disease show activation of modules containing EGLN3, a putative marker of radiotherapy resistance, and POSTN, related to the epithelialmesenquimal transition and to the development of metastasis. The set of altered functional modules indicates that tumors with aggressive profile present changes in the expression of genes implicated in communication between the microenvironment, the extracellular matrix and tumor cells. This may led to the activation of pathways which promote tumor progression through apoptosis inhibition, cell survival, proliferation, angiogenesis, invasion and tumor cell motility.