Circulating free plasma tumor DNA in patients with advanced gastric cancer receiving systemic chemotherapy.

BACKGROUND: Advanced gastric cancers are usually associated with incurable conditions for which systemic treatments are indicated. Recent studies suggest that circulating cell-free plasma DNA of tumour origin (tDNA) is a promising non-invasive biomarker that can be used to predict the prognosis and monitor the efficacy of systemic treatments in patients with certain types of cancer. We conducted a pilot study to analyse the potential role of tDNA as a biomarker in patients with advanced gastric cancer. METHODS: We included 30 patients with locally advanced unresectable or metastatic gastric cancer. We obtained samples (10 mL of total blood) from each patient every 3 months and performed concomitant CT until disease progression or death. Total cell-free circulating DNA (cfDNA) samples were measured using GeneQuant RNA/DNA Calculator-Amersham Pharmacia Biotech (Biochrom) Ltd. The cfDNA was used to evaluate the ALU DNA sequences 247 and 115. The level of tDNA was calculated from the ratio of the expression of ALU DNA sequences and the concentration of total cell-free DNA. We utilized the RECIST criteria 1.1 to evaluate the tumour response. RESULTS: Patients with advanced gastric cancer had significantly higher concentrations of cfDNA compared with normal controls (p = 0.00015), which allowed us to conclude that the cfDNA in the patients originated from the tumour. We did not find any significant correlation between the level of tDNA and OS or tumour response. However, after the first cycles of chemotherapy (at 3 months), we observed that patients with lower tDNA levels had significantly longer DFS compared with those with higher levels (Cox Regression p = 0.0228). CONCLUSIONS: At 3 months after the beginning of chemotherapy, the tDNA levels are correlated with DFS in patients with advanced gastric cancer who receive systemic chemotherapy. tDNA may be a specific, non-invasive and cost effective new biomarker for these patients.

Adhesion molecules in breast carcinoma: a challenge to the pathologist.

The role of adhesion molecules is very important both in the activation of carcinogenesis and in the differentiation of subtypes of breast carcinoma, aiding in diagnosis, prognosis and therapeutic choice in these tumors. Therefore, understanding the functions and interrelationships among these molecules is crucial to the pathologist, who often uses these factors as a resource to differentiate tumors and further classify them according to a molecular point of view. Our goal is to describe the applicability and the difficulties encountered by the pathologist in the diagnosis of breast carcinoma, discussing the most commonly used markers of adhesion in routine analyses.

Adhesion molecules in breast carcinoma: a challenge to the pathologist / Moléculas de adesão no carcinoma mamário: um desafio ao patologista

The role of adhesion molecules is very important both in the activation of carcinogenesis and in the differentiation of subtypes of breast carcinoma, aiding in diagnosis, prognosis and therapeutic choice in these tumors. Therefore, understanding the functions and interrelationships among these molecules is crucial to the pathologist, who often uses these factors as a resource to differentiate tumors and further classify them according to a molecular point of view. Our goal is to describe the applicability and the difficulties encountered by the pathologist in the diagnosis of breast carcinoma, discussing the most commonly used markers of adhesion in routine analyses.

O papel das moléculas de adesão é de suma importância tanto na ativação da carcinogênese quanto na diferenciação dos subtipos de carcinomas mamários, auxiliando no diagnóstico, no prognóstico e na escolha terapêutica nessas neoplasias. Portanto, a compreensão das funções e das inter-relações entre essas moléculas é de suma importância para o patologista, que, muitas vezes, as utiliza como recurso na diferenciação dos tumores e, consequentemente, elas auxiliam em uma posterior classificação do ponto de vista molecular. O objetivo é descrever a aplicabilidade e as dificuldades encontradas pelo médico patologista no diagnóstico de carcinoma mamário, discutindo os marcadores de adesividade mais utilizados na rotina.