NF-κB and COX-2 expression in nonmalignant endometrial lesions and cancer.

OBJECTIVES: To examine the immunohistochemical expression of cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB) in benign endometrial polyps (EPs), endometrial hyperplasia (EH), endometrial intraepithelial neoplasia (EIN), and endometrioid endometrial cancer (EC). METHODS: The immunohistochemical expression of COX-2 and NF-κB was performed using an Aperio Scanscope XT automated system in 218 patients with endometrioid EC and 107 patients with nonmalignant endometrial lesions: 53 with benign EPs, 37 with EH, and 17 with EIN. RESULTS: COX-2 and NF-κB p50 expression were significantly lower in EC compared with nonmalignant lesions. We observed significant decreased NF-κB p65 expression in EC vs EPs (P < .001) and EH (P = .014) as well as in EIN vs. EPs (P = .01). For patients with EC, COX-2 correlated positively with NF-κB p65 and NF-κB p50 (P < .001). Grade 3 tumors had a higher mean expression of NF-κB p65 (P = .03). NF-κB p50, NF-κB p65, and COX-2 expression had no impact on survival. CONCLUSIONS: We conclude that COX-2 and NF-κB expression are lower in EC compared with nonmalignant endometrial lesions. COX-2 and NF-κB expression have no prognostic value in EC.

Avaliação de resposta patológica em câncer de mama após quimioterapia neoadjuvante: padronização de protocolo adaptado / Assessment of pathological response in breast cancer after neoadjuvant chemotherapy: standardization of adapted protocol

O conceito de resposta patológica completa (pCR) é controverso. Estudos prévios utilizaram diferentes métodos de avaliação da pCR, porém não há um consenso universal sobre o melhor protocolo para o estudo das peças cirúrgicas de pacientes portadoras de carcinoma mamário submetidas ao tratamento quimioterápico neoadjuvante. Symmans et al. desenvolveram um sistema de classificação de carga residual de câncer (RCB) de mama após quimioterapia neoadjuvante, analisando a dimensão do leito tumoral primário, a porcentagem de células neoplásicas viáveis residuais no leito tumoral e o comprometimento linfonodal. Apresentamos uma proposta de avaliação da resposta patológica nos tumores de mama após quimioterapia neoadjuvante, por meio de um protocolo adaptado à nossa rotina de exame anatomopatológico de peças cirúrgicas, com base no estudo de Symmans et al.

The concept of pathologic complete response (pCR) is controversial. Previous studies used different methods of pCR assessment, but there is no universal consensus about the best protocol for the study of surgical specimens from patients with breast carcinoma undergoing neoadjuvant chemotherapy. Symmans et al. developed a classification system of residual cancer burden (RCB) after neoadjuvant chemotherapy for breast cancer analyzing the extent of primary tumor bed, the percentage of residual viable tumor cells in the tumor bed and lymph node involvement. We present a proposal for the evaluation of pathological response in breast tumors after neoadjuvant chemotherapy. Based on Symmans et al. study, it consists in a protocol adapted to our routine pathological examination of surgical specimens.

Down-regulation of ANAPC13 and CLTCL1: Early Events in the Progression of Preinvasive Ductal Carcinoma of the Breast.

Alterations in the gene expression profile in epithelial cells during breast ductal carcinoma (DC) progression have been shown to occur mainly between pure ductal carcinoma in situ (DCIS) to the in situ component of a lesion with coexisting invasive ductal carcinoma (DCIS-IDC) implying that the molecular program for invasion is already established in the preinvasive lesion. For assessing early molecular alterations in epithelial cells that trigger tumorigenesis and testing them as prognostic markers for breast ductal carcinoma progression, we analyzed, by reverse transcription-quantitative polymerase chain reaction, eight genes previously identified as differentially expressed between epithelial tumor cells populations captured from preinvasive lesions with distinct malignant potential, pure DCIS and the in situ component of DCIS-IDC. ANAPC13 and CLTCL1 down-regulation revealed to be early events of DC progression that anticipated the invasiveness manifestation. Further down-regulation of ANAPC13 also occurred after invasion appearance and the presence of the protein in invasive tumor samples was associated with higher rates of overall and disease-free survival in breast cancer patients. Furthermore, tumors with low levels of ANAPC13 displayed increased copy number alterations, with significant gains at 1q (1q23.1-1q32.1), 8q, and 17q (17q24.2), regions that display common imbalances in breast tumors, suggesting that down-regulation of ANAPC13 contributes to genomic instability in this disease.