mRNA Expression and Methylation of the RAD51, ATM, ATR, BRCA1, and BRCA2 Genes in Gastric Adenocarcinoma.

Background: Immunohistochemical prognostic significance of the homologous recombination-related proteins RAD51, ATM, BRCA1, and BRCA2 is known in gastric adenocarcinoma, one of the deadliest cancers. Objective and design: This retrospective cohort study aimed to evaluate mRNA expression and promoter methylation of some homologous recombination-related genes in this neoplasm. Methods: We evaluated mRNA expression and methylation of RAD51, ATM, ATR, BRCA1, and BRCA2 in tumor and non-tumor frozen samples from gastrectomy specimens by RT-qPCR and MS-HRM, correlating our results with previous immunohistochemistry data and prognostic features. Results: RAD51, ATR, BRCA1, BRCA2, and ATM mRNA expression was detected in 93.75% (45/48), 93.75% (45/48), 91.67% (44/48), 83.33% (40/48), and 89.58% (43/48) of the tumors; partial or complete methylation, in 94.87% (37/39), 0 (0/42), 97.56% (40/41), 100% (41/41), and 0 (0/40), respectively. Most gene pairs showed significant weak to moderate positive correlations of tumoral mRNA expression with each other: RAD51 with ATR (P = .027), BRCA1 (P < .001), and BRCA2 (P < .001); ATR with BRCA1 (P = .007), and ATM (P = .001); BRCA1 with BRCA2 (P = 0.001). BRCA1 mRNA was reduced in tumors compared with non-neoplastic mucosa (0.345 vs 1.272, P = .015) and, excluding neoadjuvant therapy cases, in T3 to T4 tumors compared with T2 (0.414 vs 0.954, P = .035). Greater tumoral RAD51 mRNA levels correlated with perineural invasion (1.822 vs 0.725, P = .010) and death (1.664 vs 0.929, P = .036), but not with survival time. There was an inverse association between nuclear immunohistochemical positivity for ATR and its mRNA levels (0.487 vs 0.907, P = .032), and no significant correlation for the other markers. Conclusions: Our results suggest RAD51, BRCA1, and BRCA2 methylation as a frequent epigenetic mechanism in gastric cancer, support the hypothesis that reduced BRCA1 expression participates in disease progression, and show an association between RAD51 mRNA and perineural invasion and mortality that may be considered unexpected, considering the former immunohistochemical studies. The lack of correlation between immunohistochemistry and mRNA, and even the inverse association, for ATR, can be seen as indicative of action of post-transcriptional or post-translational regulatory mechanisms, to be better investigated.

Prognostic Value of the Immunohistochemical Expression of RAD51 and BRCA2 in Gastric Adenocarcinoma.

Current scientific literature lacks data on the prognostic value of the expression of RAD51 and BRCA2 in gastric adenocarcinoma. Therefore, we aimed to evaluate those and other homologous recombination-related proteins (ATM, ATR, BRCA1, CHK2, γH2AX, p53) in gastric cancer, assessing their correlation with clinical prognosis. Paraffin-embedded samples were obtained from surgical specimens collected in total or subtotal gastrectomy procedures. Between 2008 and 2017, 121 patients with advanced gastric adenocarcinoma underwent surgical resection and were included in this study. Negativity for nuclear RAD51 correlated with vascular invasion, lymph node metastasis, larger tumor size, and lower overall survival and disease-free survival in univariate analysis. However, nuclear RAD51-negative cases presented better response rates to adjuvant therapy than the positive ones. Nuclear ATR negativity correlated with larger tumor size and a higher histological grade. Positivity for ATM was associated with more prolonged disease-free survival. Positivity for nuclear BRCA2 correlated with lower overall survival and diffuse histological type, whereas its high expression was associated with vascular invasion. Nevertheless, tumors positive for nuclear BRCA2 were more frequently low grade in the intestinal histological type. Our findings indicate that RAD51 and BRCA2 are valuable immunohistochemical prognostic markers in gastric adenocarcinoma.

Cervical Myelopathy Secondary to Gout: Case Report.

Gout is a crystalline arthropathy frequent in the population, but gouty spondyloarthropathy, also called axial gout, is uncommon. The current case report presents a rare case of cervical myelopathy secondary to axial gout. A 50-year-old female patient, without previous pathologies, presented with loss of strength, altered sensitivity, and pyramidal release for 2 years. The computed tomography showed a lytic image in the spinous process of C7, and signs of myelopathy with myelomalacia on magnetic resonance imaging of the cervical spine. After the surgical procedure and biopsy of the material, the diagnosis was gout, and treatment for the pathology was started, with complete improvement of the condition. The diagnosis of axial gout should be included in the spectrum of the differential diagnosis of diseases that affect the spine. Although gouty spondyloarthritis (or spondylitis) is uncommon, there is an underestimated occurrence due to the lack of investigation of the cases. The early diagnosis and treatment of the pathology can prevent patients from presenting complications of the disease, as reported in the present study.

Cervical Myelopathy Secondary to Gout: Case Report / Mielopatia cervical secundária a gota: Relato de caso

Abstract Gout is a crystalline arthropathy frequent in the population, but gouty spondyloarthropathy, also called axial gout, is uncommon. The current case report presents a rare case of cervical myelopathy secondary to axial gout. A 50-year-old female patient, without previous pathologies, presented with loss of strength, altered sensitivity, and pyramidal release for 2 years. The computed tomography showed a lytic image in the spinous process of C7, and signs of myelopathy with myelomalacia on magnetic resonance imaging of the cervical spine. After the surgical procedure and biopsy of the material, the diagnosis was gout, and treatment for the pathology was started, with complete improvement of the condition. The diagnosis of axial gout should be included in the spectrum of the differential diagnosis of diseases that affect the spine. Although gouty spondyloarthritis (or spondylitis) is uncommon, there is an underestimated occurrence due to the lack of investigation of the cases. The early diagnosis and treatment of the pathology can prevent patients from presenting complications of the disease, as reported in the present study.

Resumo A gota é uma artropatia cristalina frequente na população; entretanto, a espondiloartropatia gotosa, também chamada de gota axial, é incomum. O presente relato de caso apresenta um caso raro de mielopatia cervical secundária a gota axial. Uma paciente de 50 anos de idade, sem patologias prévias, apresentou quadro de perda de força, alteração de sensibilidade e liberação piramidal há 2 anos. A tomografia computadorizada evidenciou imagem lítica no processo espinhoso de C7, e sinais de mielopatia com mielomalácia foram observados na ressonância magnética da coluna cervical. Após o procedimento cirúrgico e biópsia do material, o diagnóstico foi de gota, e o tratamento para a patologia foi iniciado, com melhora completa do quadro. O diagnóstico de gota axial deve ser incluído no espectro do diagnóstico diferencial das doenças que acometem a coluna vertebral. Apesar de a espondiloartrite gotosa ser incomum, há uma ocorrência subestimada devido a não investigação dos casos. O diagnóstico precoce e tratamento da patologia pode evitar que pacientes apresentem complicações da doença, como a relatada no presente estudo.