RESUMO
Hormone receptor status in breast carcinoma is determined primarily to identify patients who may benefit from hormonal therapy. Estrogen receptor (ER) is one of the hormone receptor positive factors which have been recognized as a marker for which women with breast cancer would respond to hormone treatment. We propose a system to classify cells in ER-stained whole slide breast carcinoma images according to their staining strength using convolutional neural network (CNN). The proposed CNN multiclass classifier was tested on a region of 1200 cells, and achieved very promising results, with overall accuracy of 88.8% and AUC score of 97.5%. The proposed system is useful for use in hormone receptor testing, where the outcomes are used to decide whether the cancer is likely to respond to hormonal therapy or other treatments.
Assuntos
Neoplasias da Mama/classificação , Redes Neurais de Computação , Receptores de Estrogênio/análise , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Feminino , HumanosRESUMO
BRCA1, a well-known tumor suppressor with multiple interacting partners, is predicted to have diverse biological functions. However, so far its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low-penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions. Using this rationale, we studied the R1699Q variant of BRCA1, a potentially moderate-risk variant, and found that it does not impair DNA damage repair but abrogates the repression of microRNA-155 (miR-155), a bona fide oncomir. Mechanistically, we found that BRCA1 epigenetically represses miR-155 expression via its association with HDAC2, which deacetylates histones H2A and H3 on the miR-155 promoter. We show that overexpression of miR-155 accelerates but the knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Our findings demonstrate a new mode of tumor suppression by BRCA1 and suggest that miR-155 is a potential therapeutic target for BRCA1-deficient tumors.
Assuntos
Proteína BRCA1/metabolismo , Reparo do DNA/fisiologia , Epigênese Genética/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/metabolismo , Análise de Variância , Proteína BRCA1/genética , Southern Blotting , Imunoprecipitação da Cromatina , Reparo do DNA/genética , Epigênese Genética/genética , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Histona Desacetilase 2/metabolismo , Humanos , Imuno-Histoquímica , Imunoprecipitação , Hibridização In Situ , Análise em Microsséries , Mutação de Sentido Incorreto/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Isosulfan blue is not available for clinical use in Malaysia. This study describes the use of methylene blue as an alternative to isosulfan blue in colorectal sentinel node mapping. METHODS: Methylene blue dye was injected around colonic and rectal tumours and the first blue-stained nodes were suture tagged and harvested after standard colorectal resection. Standard histopathological examination was then carried out to detect nodal metastasis. All negative sentinel lymph nodes (SLN) were subjected to 10 further step sectioning and immunoperoxidase staining for cytokeratin 20 to detect tumour deposits. RESULTS: Thirty-one patients were enrolled from August 2005 to July 2006. Twenty-five attempts at identifying the SLN were successful (80.7%). Of the 18 (58.1%) who had nodal metastases (stage III), 3 had negative SLN but positive other lymph nodes (false-negative rate of 21.4%). In one (4%), the SLN was the exclusive site of metastasis. CONCLUSION: Methylene blue can be used as an alternative sentinel node marker for rectal cancer (above the peritoneal reflection) and colonic cancer.