RESUMO

Prediction of lung cancer metastasis relies on post-resection assessment of tumor histology, which is a severe limitation since only a minority of lung cancer patients are diagnosed with resectable disease. Therefore, characterization of metastasis-predicting biomarkers in pre-resection small biopsy specimens is urgently needed. Here we report a biomarker consisting of the phosphorylation of the retinoblastoma protein (Rb) on serine 249 combined with elevated p39 expression. This biomarker correlates with epithelial-to-mesenchymal transition traits in non-small cell lung carcinoma (NSCLC) cells. Immunohistochemistry staining of NSCLC tumor microarrays showed that strong phospho-Rb S249 staining positively correlated with tumor grade specifically in the squamous cell carcinoma (SCC) subtype. Strong immunoreactivity for p39 positively correlated with tumor stage, lymph node invasion, and distant metastases, also in SCC. Linear regression analyses showed that the combined scoring for phospho-Rb S249, p39 and E-cadherin in SCC is even more accurate at predicting tumor staging, relative to each score individually. We propose that combined immunohistochemistry staining of NSCLC samples for Rb phosphorylation on S249, p39, and E-cadherin protein expression could aid in the assessment of tumor staging and metastatic potential when tested in small primary tumor biopsies. The intense staining for phospho-Rb S249 that we observed in high grade SCC could also aid in the precise sub-classification of poorly differentiated SCCs.

Assuntos

Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas do Citoesqueleto/biossíntese , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Proteína do Retinoblastoma/metabolismo , Biomarcadores Tumorais/genética , Caderinas/biossíntese , Caderinas/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Adesão Celular/genética , Linhagem Celular Tumoral , Proteínas do Citoesqueleto/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Gradação de Tumores , Metástase Neoplásica , Fosforilação , Proteína do Retinoblastoma/genética

RESUMO

BACKGROUND/AIM: Microsatellite instability (MSI) results from genetic alterations involving the mismatch repair (MMR) genes MLH1, PSM2, MSH2, and MSH6. MSI has been implicated in both sporadic CRC and Lynch syndrome. The aim of the study was to assess the frequency of alterations in MMR protein expression in both primary colorectal cancer and precursor lesions among Puerto Rican patients. PATIENTS AND METHODS: A retrospective study of 84 Puerto Rican patients was performed to assess the frequency of MMR protein expression alterations in both primary CRC and precursor lesions using tissue microarray and immunohistochemistry. RESULTS: The loss of expression of both MLH1 and PMS2 proteins was present in 6.3% of adenomas, 9.1% of adenomas with high-grade dysplasia and 9.4% of colon adenocarcinomas. Negative nuclear staining for both MSH2 and MSH6 proteins was found in 2.4% of colon adenocarcinomas. CONCLUSION: When compared to prior reports, this study suggests a lower frequency of MSI among the Puerto Rican population. The higher prevalence of MLH1 mutations correlates with previous studies of protein expression among the Hispanic community including Colombian, Uruguay and Brazilian populations.

Assuntos

Adenocarcinoma/metabolismo , Adenoma/metabolismo , Neoplasias do Colo/metabolismo , Hispânico ou Latino/genética , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Mutação , Adenocarcinoma/epidemiologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenoma/epidemiologia , Adenoma/genética , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/genética , Feminino , Seguimentos , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mucosa/metabolismo , Proteína 2 Homóloga a MutS/genética , Prognóstico , Porto Rico/epidemiologia , Estudos Retrospectivos

RESUMO

Significant cancer health disparities exist in the United States and Puerto Rico. While numerous initiatives have been implemented to reduce cancer disparities, regional coordination of these efforts between institutions is often limited. To address cancer health disparities nation-wide, a series of regional transdisciplinary networks through the Geographic Management Program (GMaP) and the Minority Biospecimen/Biobanking Geographic Management Program (BMaP) were established in six regions across the country. This paper describes the development of the Region 3 GMaP/BMaP network composed of over 100 investigators from nine institutions in five Southeastern states and Puerto Rico to develop a state-of-the-art network for cancer health disparities research and training. We describe a series of partnership activities that led to the formation of the infrastructure for this network, recount the participatory processes utilized to develop and implement a needs and assets assessment and implementation plan, and describe our approach to data collection. Completion, by all nine institutions, of the needs and assets assessment resulted in several beneficial outcomes for Region 3 GMaP/BMaP. This network entails ongoing commitment from the institutions and institutional leaders, continuous participatory and engagement activities, and effective coordination and communication centered on team science goals.

Assuntos

Acessibilidade aos Serviços de Saúde/normas , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/normas , Saúde das Minorias/normas , Neoplasias/prevenção & controle , Regionalização da Saúde/normas , Negro ou Afro-Americano/estatística & dados numéricos , Redes Comunitárias/organização & administração , Acessibilidade aos Serviços de Saúde/organização & administração , Disparidades em Assistência à Saúde/organização & administração , Hispânico ou Latino/estatística & dados numéricos , Humanos , Relações Interinstitucionais , Saúde das Minorias/estatística & dados numéricos , Avaliação das Necessidades/organização & administração , Avaliação das Necessidades/normas , Neoplasias/diagnóstico , Neoplasias/etnologia , Porto Rico/epidemiologia , Regionalização da Saúde/métodos , Regionalização da Saúde/organização & administração , Sudeste dos Estados Unidos/epidemiologia

RESUMO

The 1st Puerto Rico Biobanking Workshop took place on August 20st, 2014 in the Auditorium of the Comprehensive Cancer Center of the University of Puerto Rico, Medical Sciences Campus in San Juan Puerto Rico. The program for this 1-day, live workshop included lectures by three biobanking experts, followed by presentations from existing biobanks in Puerto Rico and audience discussion. The need for increasing biobanking expertise in Puerto Rico stems from the fact that Hispanics in general are underrepresented in the biobanks in existence in the US, which limits the research conducted specifically to understand the molecular differences in cancer cells compared to other better studied populations. In turn, this lack of information impairs the development of better diagnostic and therapeutic approaches for our population. Dr. James Robb, M.D., F.C.A.P., consulting pathologist to the National Cancer Institute (NCI) and the Office of Biorepositories and Biospecimen Research (OBBR), opened the workshop with a discussion on the basic aspects of the science of biobanking (e.g., what is a biobank; its goals and objectives; protocols and procedures) in his talk addressing the importance of banking tissues for advancing biomedical research. Next, Dr. Gustavo Stefanoff, from the Cancer Institutes Network of Latin America (RINC by its name in Spanish), explained the mission, objectives, and structure of the Network of Latin-American and Caribbean Biobanks (REBLAC by its name in Spanish), which despite limited resources and many challenges, currently accrue high quality human tissue specimens and data to support cancer research in the region. Dr. Robert Hunter-Mellado, Professor of Internal Medicine, Universidad Central del Caribe, followed with an examination of the ethical and regulatory aspects of biobanking tissues for future research, including informed consent of subjects; protection of human subjects rights; and balancing risks and benefit ratios. In the afternoon, the directors of existing biobanks in Puerto Rico (the Puerto Rico Biobank, the Comprehensive Cancer Center biobank, and an HIV-focused biobank at Universidad Central del Caribe) presented their experiences and challenges with establishing biobanks for research in Puerto Rico. In sum, this workshop presented opportunities to share knowledge in the science of biobanking, for further training, and of networking among the participants (34 from 4 different institutions), which will strengthen the collaborative links between investigators studying cancer in Latin America, the Caribbean, and the US.

Assuntos

Bancos de Espécimes Biológicos/organização & administração , Pesquisa Biomédica/métodos , Congressos como Assunto , Neoplasias/diagnóstico , Humanos , Porto Rico

RESUMO

Population-based studies are important to address emerging issues in health disparities among populations. The Partnership between the Moffitt Cancer Center (MCC) in Florida and the Ponce School of Medicine and Health Sciences (PSMHS) in Puerto Rico (the PSMHS-MCC Partnership) was developed to facilitate high-quality research, training, and community outreach focusing on the Puerto Rican population in the island and in the mainland, with funding from the National Cancer Institute. We report here the establishment of a Tissue Biobank at PSMHS, modeled after the MCC tissue biorepository, to support translational research projects on this minority population. This facility, the Puerto Rico Tissue Biobank, was jointly developed by a team of basic and clinical scientists from both institutions in close collaboration with the administrators and clinical faculty of the tissue accrual sites. The efforts required and challenges that needed to be overcome to establish the first functional, centralized cancer-related biobank in Puerto Rico, and to ensure that it continuously evolves to address new needs of this underserved Hispanic population, are described. As a result of the collaborative efforts between PSMHS and MCC, a tissue procurement algorithm was successfully established to acquire, process, store, and conduct pathological analyses of cancer-related biospecimens and their associated clinical-pathological data from Puerto Rican patients with cancer recruited at a tertiary hospital setting. All protocols in place are in accordance with standard operational procedures that ensure high quality of biological materials and patient confidentiality. The processes described here provide a model that can be applied to achieve the establishment of a functional biobank in similar settings.