Cancer risk is highly variable in carriers of the common TP53-R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (P = 0.003) and subsequent malignancies (P = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic TP53 variants, whereas XAF1-E134* is markedly attenuated in this activity. We propose that cosegregation of XAF1-E134* and TP53-R337H mutations leads to a more aggressive cancer phenotype than TP53-R337H alone, with implications for genetic counseling and clinical management of hypomorphic TP53 mutant carriers.

BackgroundConventional axillary lymph node dissection (ALND) has recently become less radical. The treatment morbidity effects of reduced ALND aggressiveness are unknown. This article investigates the prevalence of the main complications of ALND: lymphedema, range-of-motion restriction, and arm paresthesia and pain.MethodsThis cross-sectional study included 200 women with invasive breast cancer who underwent breast-conserving surgery (82.5%, n = 165) or mastectomy (17.5%, n = 35) with ALND from 2007 to 2011. Arm perimetry was used to assess lymphedema, defined as a difference >2 cm in the upper arm circumference between the nonsurgical and surgical arms. Range-of-motion restriction was assessed by evaluating the degree of arm abduction. Paresthesia was measured in the inner and proximal arm regions. Arm pain was assessed by directly questioning the patients and defined as either present or absent.ResultsThe average (±SD) time between ALND and morbidity evaluation was 35 ± 18 months (range, 7-60 months). The average dissected lymph node number per patient was 14 ± 4 (range, 6-30 lymph nodes). Only 3.5% (n = 7) of the patients presented with lymphedema. Single-incision approaches to breast tumor and ALND (P = 0.04) and the presence of a postoperative seroma (P = 0.02) were associated with lymphedema in univariate analysis. Paresthesia was the most frequent side effect observed (53% of patients, n = 106). This complication was associated with increased age (P < 0.0001) and a larger dissected lymph node number (P = 0.01) in univariate and multivariate analysis. Additionally, 24% (n = 48) of patients had noticeable limited arm abduction. Among the patients, 27.5% (n = 55) experienced sporadic arm pain corresponding to the surgically treated armpit. In multivariate analysis, the pain risk was 1.9-fold higher in patients who underwent ALND corresponding to their dominant arm (95% CI, 1.0-3.7, P = 0.04).ConclusionConventional ALND in breast cancer patients can result in unwanted complications. However, the current lymphedema prevalence is lower than that of the other analyzed side effects.

PurposeThe present study aimed to measure the thickness of the subcutaneous adipose tissue (SAT) at the site of the surgical incision for axillary lymph node dissection (ALND) and to record potential anatomical variations in the medial cutaneous nerve of the arm (MCNA), the intercostobrachial nerve (ICBN), the lateral thoracic vein (LTV), the lateral thoracic artery (LTA) and the pectoral muscle pedicle (PMP), considering that some details of the anatomy of these structures within the axilla are still unclear.MethodsA prospective study was conducted in 100 consecutive patients with breast cancer who underwent ALND as part of surgical treatment. The anatomy of the dissected axilla was video recorded.ResultsThe SAT thickness ranged from 8 mm to 60 mm, with an average thickness of 25.9 mm. A positive correlation was observed between the SAT thickness and the body mass index (BMI) of the evaluated patients (r = 0.68; p < 0.0001). The MCNA was the anatomical structure that was least commonly observed in the axilla (22% of cases), while the PMP was the most constant element, identified in 100% of cases. All of the studied anatomical structures observed within the axilla showed variation in at least one of the aspects analyzed, i.e., the point of entry and exit, path, number and location of divisions or branches.ConclusionThe present study demonstrated wide variation in thickness of the SAT overlying the axilla and identified the existence of broad normative anatomical variation of the axilla.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-306) contains supplementary material, which is available to authorized users.

The R337H is a TP53 germline pathogenic variant that has been associated with several types of cancers, including breast cancer. Our main objective was to determine the frequency of the R337H variant in sporadic breast cancer patients from Paraná state, South Brazil, its association with prognosis and its impact in genomic instability. The genotyping of 805 breast cancer tissues revealed a genotypic and allelic frequency of the R337H variant of 2.36% and 1.18%, respectively. In these R337H+ cases a lower mean age at diagnosis was observed when compared to the R337H-cases. Array-CGH analysis showed that R337H+ patients presented a higher number of copy number alterations (CNAs), compared to the R337H−. These CNAs affected genes and miRNAs that regulate critical cancer signaling pathways; a number of these genes were associated with survival after querying the KMplot database. Furthermore, homozygous (R337H+/R337H+) fibroblasts presented increased levels of copy number variants when compared to heterozygous or R337H− cells. In conclusion, the R337H variant may contribute to 2.36% of the breast cancer cases without family cancer history in Paraná. Among other mechanisms, R337H increases the level of genomic instability, as evidenced by a higher number of CNAs in the R337H+ cases compared to the R337H−.

INTRODUÇÃO: A fitoterapia vem despertando crescente interesse na comunidade científica em relação às suas potenciais propriedades cicatriciais. Poucos são os estudos com metodologia científica existentes na literatura, constituindo-se assim um campo aberto para novas investigações. OBJETIVOS: Analisar a ação da Jatropha gossypiifolia L. (pião roxo) na cicatrização de anastomose colônica em ratos. MÉTODOS: Quarenta ratos Wistar foram submetidos à secção de toda a circunferência do cólon, sendo logo anastomosada com oito pontos separados usando fio monofilamentar de polipropileno 6-0. Aleatoriamente, os animais foram distribuídos em grupo controle (GC), contendo 20 ratos, nos quais foi administrada solução de cloreto de sódio a 0,9% por via intraperitoneal (1ml/kg) e grupo Jatropha (GJ), também com 20 nos quais foi administrado o extrato hidroalcoólico de Jatropha gossypiifolia L. por via intraperitoneal (1ml/kg). Cada um dos grupos foi subdividido em dois subgrupos de dez animais de acordo com a data de sacrifício, três e sete dias (GC3/ GC7 e GJ3/GJ7). Após o sacrifício foi retirada parte do cólon compreendendo 1 cm acima e abaixo da anastomose e submetido ao teste de resistência à insuflação de ar atmosférico. A seguir, foi aberta e retirada uma porção de 1,0 x 0,5cm de tamanho colocada em formol a 10% para análise histológica, na qual foram usadas a coloração de Hematoxilina-Eosina e o Tricrômico de Masson. RESULTADOS: Na avaliação do teste de pressão de ruptura entre os grupos houve significância estatística quando avaliados em relação à data de sacrifício Assim no terceiro dia a média no GC (25,4 mmHg.) e no GJ (76,4 mmHg.) estabeleceu p = 0.013, e no sétimo dia a média no GC (187,3 mmHg.) e no GJ (135,1 mmHg.) estabeleceu p = 0.014. Ao analisar as variáveis microscópicas entre os grupos no 3º dia, somente não houve diferença significativa nas variáveis edema e polimorfonucleares. Já no 7º dia todas as variáveis analisadas apresentaram diferença significativa. CONCLUSÕES: Na resistência mecânica pôde-se concluir que houve influência positiva da jatropha na aquisição de força na anastomose no terceiro dia. Entretanto, no sétimo dia o GC suplantou siginificativamente a pressão de ruptura obtida no GJ, sugerindo diminuição da ação da Jatropha em fase mais avançada da cicatrização. Na avaliação histológica pôde-se verificar avanço no processo inflamatório agudo no GJ3 em relação ao GC3, mantendo-se ainda mais intenso na fase crônica quando comparados os dois grupos no sétimo dia.