Multiplatform Investigation of Plasma and Tissue Lipid Signatures of Breast Cancer Using Mass Spectrometry Tools.

Plasma and tissue from breast cancer patients are valuable for diagnostic/prognostic purposes and are accessible by multiple mass spectrometry (MS) tools. Liquid chromatography-mass spectrometry (LC-MS) and ambient mass spectrometry imaging (MSI) were shown to be robust and reproducible technologies for breast cancer diagnosis. Here, we investigated whether there is a correspondence between lipid cancer features observed by desorption electrospray ionization (DESI)-MSI in tissue and those detected by LC-MS in plasma samples. The study included 28 tissues and 20 plasma samples from 24 women with ductal breast carcinomas of both special and no special type (NST) along with 22 plasma samples from healthy women. The comparison of plasma and tissue lipid signatures revealed that each one of the studied matrices (i.e., blood or tumor) has its own specific molecular signature and the full interposition of their discriminant ions is not possible. This comparison also revealed that the molecular indicators of tissue injury, characteristic of the breast cancer tissue profile obtained by DESI-MSI, do not persist as cancer discriminators in peripheral blood even though some of them could be found in plasma samples.

Can MTHFR C677T and A1298C Polymorphisms Alter the Risk and Severity of Sporadic Breast Cancer in Brazilian Women?

INTRODUCTION: Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) modify the risk and severity of sporadic breast cancer (BC). In this context, the MTHFR C677T and A1298C polymorphisms have been associated with risk and severity of sporadic BC. PATIENTS AND METHODS: In total, 253 women with BC and 257 controls were enrolled in this study. Polymorphisms were analyzed using restriction fragment length polymorphism - polymerase chain reaction. Epidemiology, tumor characteristics, and reproductive factors were considered in the analysis. Statistical tests included the χ2 test, the Fisher exact test, and the Mann-Whitney and Kruskal-Wallis tests, or parametric equivalents. RESULTS: MTHFR polymorphisms were not a risk factor for BC. The 677CC genotype was associated with distant metastasis (odds ratio [OR] = 5.311; 95% confidence interval [CI] = 1.124-25.09) and lower estrogen receptor expression, whereas the 1298AA genotype was associated with stage 0 (OR = 0.244; 95% CI = 0.077-0.771) and increased estrogen receptor expression. In haplotype analysis, 677CC/1298AA was associated with hypertension (OR = 1.979; 95% CI = 1.036-3.782), and 677CT/1298AC was associated with invasive carcinoma of no special type (OR = 0.472; 95% CI = 0.243-0.918) and stage 0 (OR = 3.476; 95% CI = 1.341-10.47). CONCLUSION: The MTHFR C677T and A1298C polymorphisms do not alter the risk of BC, but are associated with the clinical severity of BC.

Variants of estrogen receptor alpha and beta genes modify the severity of sporadic breast cancer.

INTRODUCTION: Reproductive factors pose a risk for sporadic breast cancer (BC) development owing to the lifetime exposure to estrogen, a hormone responsible for cell proliferation in the breast. Because variants of the estrogen receptor (ER) alpha and beta genes have been associated with BC risk in numerous populations, the objective of the study was to determine whether the risk and severity of sporadic BC was associated with the rs2228480 (ESR1) and rs4986938 (ESR2) variants in a Brazilian population. METHODS: A total of 253 DNA samples from sporadic BC patients and 257 DNA samples from healthy controls were studied. The samples were genotyped by PCR-RFLP. Epidemiological, clinical, and reproductive factors were analyzed. Statistical tests conducted included the χ2 test, Fisher's exact test, and Mann-Whitney and Kruskal-Wallis tests or their parametric equivalents. RESULTS: There was a high frequency of the rs2228480*GG genotype among the ER-positive tumors (OR=2.13; 95% CI=1.189-3.816) and it showed minor association with clinical stage 0 (OR=0.324; 95% CI=0.116-0.904). The rs2228480*GA genotype was associated with minor ER expression, whereas rs2228480*GG was associated with high expression of the progesterone receptor (PR). The frequency of rs4986938*GA was high among women who breastfed (OR=2.11; 95% CI=1.203-3.702), and it showed high association with clinical stage 0 (OR=4.383; 95% CI=1.606-11.96) whereas it had minor association with systemic arterial hypertension (OR=0.53; 95% CI=0.319-0.880). The rs2228480*GG/rs4986938*GG haplotype occurred at a low frequency among women who breastfed (OR=0.525; 95% CI=0.298-0.924) but it was associated with a high expression of PR. CONCLUSION: The rs2228480 and rs4986938 variants did not alter sporadic BC risk, but they did modulate the BC severity.

Avaliação laboratorial das interleucinas: prognóstico e monitoramento de diferentes doenças humanas / Laboratory evaluation of interleukins: prediction and follow up of different human diseases

Em laboratórios de análises clínicas, interleucinas (IL) são quantificadas por diferentes metodologias como as variantes dos ensaios imunoenzimáticos (ELISA, EIA, MEIA,), quimioluminescência (CLIA), e eletroquimioluminescência (ECL). No entanto, no Brasil, a quantificação das IL está restrita a poucos laboratórios clínicos, uma vez que o custo dos exames é alto em comparação a outros comumente utilizados. Sabe-se que a detecção de algumas IL pode antecipar o prognóstico e a gravidade das patologias, possibilitando a prescrição de tratamentos eficazes, evitando o agravamento do quadro clínico dos pacientes. Em doenças de desenvolvimento crônico, pode-se predizer desde o grau da lesão tissular até a resolução dos quadros. O objetivo deste trabalho foi apresentar a utilização das dosagens de interleucinas no prognóstico e monitoramento de diferentes doenças humanas, através das metodologias de ELISA, CLIA e ECL.