RESUMO
Areas of a junction between two types of epithelia are known to be cancer-prone in many organ systems. However, mechanisms for preferential malignant transformation at the junction areas remain insufficiently elucidated. Here we report that inactivation of tumor suppressor genes Trp53 and Rb1 in the gastric squamous-columnar junction (SCJ) epithelium results in preferential formation of metastatic poorly differentiated neoplasms, which are similar to human gastroesophageal carcinoma. Unlike transformation-resistant antral cells, SCJ cells contain a highly proliferative pool of immature Lgr5-CD44+ cells, which are prone to transformation in organoid assays, comprise early dysplastic lesions, and constitute up to 30% of all neoplastic cells. CD44 ligand osteopontin (OPN) is preferentially expressed in and promotes organoid formation ability and transformation of the SCJ glandular epithelium. OPN and CD44 overexpression correlate with the worst prognosis of human gastroesophageal carcinoma. Thus, detection and selective targeting of the active OPN-CD44 pathway may have direct clinical relevance.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Junção Esofagogástrica/metabolismo , Receptores de Hialuronatos/metabolismo , Osteopontina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Neoplasias Gástricas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica , Estudos de Coortes , Junção Esofagogástrica/patologia , Feminino , Humanos , Receptores de Hialuronatos/genética , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Osteopontina/genética , Receptores Acoplados a Proteínas G/genética , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Racial disparities among patients who receive breast mastectomy and reconstruction have not been well characterized. METHODS: Records of patients undergoing breast extirpative and reconstructive surgery at a high-volume university-affiliated hospital over 5 consecutive years were reviewed. Patient demographics, breast cancer profiles, reconstructive modality, and outcomes were compared by race. RESULTS: A total of 1045 patients underwent 1678 breast reconstructions during the five-year period. Mean age and standard deviation was 49.8⯱â¯10.6 years with a BMI of 27.9⯱â¯6.5. Hispanic and African American patients had significantly higher BMIs (pâ¯<â¯0.001), higher rates of ASA class III or IV (pâ¯=â¯0.025), obesity, diabetes, hypertension (pâ¯<â¯0.001 for these three comparisons), and smoking (pâ¯=â¯0.003), and had more prior abdominal surgeries (pâ¯=â¯0.007). Comparing oncologic characteristics, this population subset had higher rates of neoadjuvant chemotherapy (pâ¯=â¯0.036), history of radiation (pâ¯=â¯0.016), and were more likely to undergo modified radical mastectomy (pâ¯=â¯0.002) over nipple-sparing mastectomy (pâ¯=â¯0.035). Reconstructive complications revealed a higher overall complication rate (pâ¯=â¯0.023), higher rates of partial mastectomy flap necrosis (pâ¯=â¯0.043), as well as arterial (pâ¯=â¯0.009) and venous insufficiency (pâ¯=â¯0.026) during microvascular reconstruction among Hispanic and African American patients. CONCLUSIONS: Compared to other patients, the present study identifies higher comorbidity burdens, higher rates of prior radiation and neoadjuvant chemotherapy, and higher post-surgical complication rates among Hispanic and African American patients with breast cancer.
