RESUMO
OBJECTIVES: Management of colorectal cancer warrants mutational analysis of KRAS/NRAS when considering anti-epidermal growth factor receptor therapy and BRAF testing for prognostic stratification. In this multicenter study, we compared a fully integrated, cartridge-based system to standard-of-care assays used by participating laboratories. METHODS: Twenty laboratories enrolled 874 colorectal cancer cases between November 2017 and December 2018. Testing was performed on the Idylla automated system (Biocartis) using the KRAS and NRAS-BRAF cartridges (research use only) and results compared with in-house standard-of-care testing methods. RESULTS: There were sufficient data on 780 cases to measure turnaround time compared with standard assays. In-house polymerase chain reaction (PCR) had an average testing turnaround time of 5.6 days, send-out PCR of 22.5 days, in-house Sanger sequencing of 14.7 days, send-out Sanger of 17.8 days, in-house next-generation sequencing (NGS) of 12.5 days, and send-out NGS of 20.0 days. Standard testing had an average turnaround time of 11 days. Idylla average time to results was 4.9 days with a range of 0.4 to 13.5 days. CONCLUSIONS: The described cartridge-based system offers rapid and reliable testing of clinically actionable mutation in colorectal cancer specimens directly from formalin-fixed, paraffin-embedded tissue sections. Its simplicity and ease of use compared with other molecular techniques make it suitable for routine clinical laboratory testing.
Assuntos
Neoplasias Colorretais/genética , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Padrão de Cuidado , Fatores de TempoRESUMO
Male breast cancer occurs rarely, comprising <1% of breast cancers. Due to the low incidence of male breast cancer, clinical trials of this disease are lacking. Therefore, therapeutic strategies utilized in the management of female breast cancer are often applied to male patients with breast cancer. Specifically, clinical outcomes using CDK 4/6 inhibitors require further investigation in male patients. To the best of our knowledge, the present report presents the first known case of a male patient treated with second line Abemaciclib, Lupron and Fulvestrant, producing complete remission. To the best of our knowledge this is also the first report of complete remission in a male breast cancer patient with a regimen utilizing a CDK 4/6 inhibitor.
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Pancreatic adenocarcinoma is a genetic disease showing somatic mutations of multiple genes, including SMAD4. SMAD4 is a tumor suppressor gene that is inactivated in a sub-set of pancreatic adenocarcinoma, either by the intragenic mutation of one allele in combination with the loss of the other allele or by homozygous deletion of both alleles. This study examines SMAD4 expression in fine-needle aspiration cell blocks from patients with pancreatic adenocarcinoma, as well as a variety of human cancers, in order to assess its viability as a tumor marker. A total of 100 patients with pancreatic adenocarcinoma, with diagnostic material from fine-needle aspiration cell blocks were selected for this study. In addition cancers from different sites were examined in multitumor tissue microarrays, which included two tissue cores from neoplastic surgical resection specimens. Cancers studied included endometrium (n = 100), colon (n = 100), ovary (n = 100), lung (n = 100), breast (n = 100), and malignant melanoma (n = 100). The sections were immunostained with SMAD4 using pressure cooker antigen retrieval labeled polymer horseradish peroxidase (DAKO), and the DAKO autostainer. Immunohistochemical expression was scored as negative, 1+, 2+, 3+. Only 2+ and 3+ staining was considered as positive staining. SMAD4 staining was nuclear and the results for tumor cell positivity for primary sites studied are as follows: Pancreas (80/100; 80%), endometrium (0/100; 0%), colon (0/100; 0%), ovary (3/100; 3%), lung (0/100; 0%), breast (2/100; 2%), and malignant melanoma (4/100; 4%). This study suggests that SMAD4 is an important marker for confirming a diagnosis of pancreatic adenocarcinoma as a primary tumor, as well as when it presents as a metastatic tumor on small fine-needle aspirate samples.
Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Proteína Smad4/metabolismo , Adenocarcinoma/patologia , Alelos , Biópsia por Agulha Fina , Feminino , Humanos , Mutação/genética , Neoplasias/metabolismo , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Proteína Smad4/genéticaRESUMO
PURPOSE: Melanoma is the most common cause of death from cutaneous malignancy, and is the cancer that is most rapidly rising in incidence. Because current therapeutic methods for metastatic melanoma are poorly efficacious, enhanced understanding of signal transduction in melanoma progression is warranted. Prior experimental studies in murine models and human tissues have shown a correlation among activation of mitogen activated protein kinase (MAPK) signaling, angiogenesis, and tumorigenesis. Because of these findings, we wanted to assess the role of MAPK signaling in melanoma progression and angiogenesis. EXPERIMENTAL DESIGN: We studied expression of phosphorylated (active) MAPK and two target genes known to be induced by MAPK signaling, tissue factor and vascular endothelial growth factor, in 131 melanocytic lesions, ranging from atypical nevi to metastatic melanoma. RESULTS: We observed little staining for activated (phosphorylated) MAPK and low amounts of angiogenesis in atypical nevi, but angiogenesis and MAPK activation were activated in radial growth melanoma and in later stage lesions. CONCLUSIONS: Our findings implicate MAPK activation as an early event in melanoma progression, and MAPK may be a potential target for pharmacologic intervention.