The potential of molecular markers to improve interventions through the natural history of oesophageal squamous cell carcinoma

Abstract

EC (oesophageal cancer) is one of the ten most frequent and fatal tumours worldwide and ESCC (oesophageal squamous cell carcinoma) accounts for about 80% of the cases. The first symptoms of ESCC arise late during the progression of the disease and, therefore, the diagnosis is usually done in advanced stages. This leads to an inefficient treatment and consequently to a poor prognosis. Thus, a comprehensive knowledge of ESCC biology is of major importance to identify risk factors, especially in high-incidence areas and biomarkers which could enable ESCC prevention and interventions throughout the natural history of the disease. In this review, we present the current knowledge regarding ESCC aetiology as well as the different genetic and epigenetic alterations already described in this tumour. We also discuss how these alterations could be used to anticipate ESCC diagnosis as well as how they can help improving treatment. A molecular natural history of the disease is proposed pointing out potential markers that may improve interventions at different points of ESCC development. Only when the different layers of complexity behind this tumour are elucidated, it will be possible to successfully perform prevention at different levels.

High Mobility Group A proteins in esophageal carcinomas

“…This result sounds very interesting, since the differential expression pattern of HMGA1 and HMGA2 in EAC and ESCC could reflect the complex and widely divergent etiology and genesis of these tumors. 17,8 Moreover, the correlation of a type of HMGA with a specific histotype further suppports the diversity between HMGA1 and HMGA2 as already suggested from their respective KO mice. Interestingly, preliminary results show an increased expression of HMGA2, but not HMGA1, in squamous skin (Chiappetta et al, manuscript in preparation) and larynx (Palumbo J unior et al, manuscript in preparation) carcinomas, suggesting that the HMGA2 specific induction is associated somehow with the squamous histotype.…”

“…Other related factors are nutritional deficiencies, low socioeconomic status and poor oral hygiene. ESCC is more incident among men than women, what could be explained by the greater exposition of men to the risk factors associated with this disease (reviewed in 8 ).…”

“…In our study we demonstrate that HMGA2 mRNA expression was capable of clearly distinguishing ESCC from healthy esophageal tissue and tumor surrounding mucosa that, even though histologically normal, already harbors molecular alterations not found in esophageal healthy tissues. 8 In this way, the identification of a molecular marker differentially expressed in ESCC samples, tumor surrounding mucosa and healthy esophageal tissue represents a potential improvement for ESCC early detection in the near future. Nonetheless, despite the high levels of HMGA2 transcript and protein detected in the ESCC samples evaluated in our study, its overexpression did not significantly impact on ESCC patients overall survival.…”

Organização e práticas da assistência farmacêutica em oncologia no âmbito do Sistema Único de Saúde

“…"In reality, it is more the question of the value that APAC 'institutes' [adopts] for that treatment ... no matter how much we know that everyone has breast cancer, breast cancers are not the same [...] It is possible to perceive the interviewee's concerns in trying not to burden the system, but to promote rationality in the process. Knowing that cancer has multifactorial and genetic causes, performing molecular diagnosis is extremely relevant before the definition of the therapeutic indication 21 . This strategy is also important to foster research and improve the oncology care policies and the process of health technology assessment 22 .…”

FOXA1 and CK7 expression in esophageal squamous cell carcinoma and its prognostic significance

“…Because of the lack of early clinical symptoms of ESCC patients and the slow development of symptoms, ESCC invasion ability is very strong and results in a high degree of malignancy of ESCC and poor prognosis. Epidemiological investigation showed that the 5-year survival rate of patients with ESCC was only about 35% [3][4][5][6]. In order to reduce the morbidity and mortality of patients with ESCC, it is urgent to select suitable tumor markers.…”