RESUMO
BACKGROUND: BRAFV600 , NRAS, TP53, and BRAFNon-V600 are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAFV600 and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAFNon-V600 mutations. METHODS: This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanoma patients who had undergone clinically indicated molecular testing (n = 926). RESULTS: The prevalence of BRAFV600 , NRAS, TP53, and BRAFNon-V600 mutations was 43%, 21%, 19%, and 7%, respectively. The presence of a TP53 mutation was associated with older age (P = .019), a head and neck primary tumor site (P = .0001), and longer overall survival (OS) from the diagnosis of stage IV disease in univariate (P = .039) and multivariate analyses (P = .015). BRAFNon-V600 mutations were associated with older age (P = .005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAFNon-V600 mutations correlated significantly with OS with frontline ipilimumab treatment, and the TP53 status was not significantly associated with outcomes with frontline BRAF inhibitor therapy. Eleven patients with BRAFNon-V600 mutations were treated with a BRAF inhibitor. Three patients were not evaluable for a response because of treatment cessation for toxicities; the remaining patients had disease progression as the best response to therapy. CONCLUSIONS: These results add to the understanding of the clinical features associated with TP53 and BRAFNon-V600 mutations in advanced cutaneous melanoma patients, and they support the rationale for evaluating the prognostic significance of TP53 in other cohorts of melanoma patients. Cancer 2017;123:1372-1381. © 2016 American Cancer Society.
Assuntos
Melanoma/diagnóstico , Melanoma/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Criança , Análise Mutacional de DNA , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Taxa de Mutação , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidade , Carga Tumoral , Adulto Jovem , Melanoma Maligno CutâneoRESUMO
Numerous cutaneous manifestations have been associated with use of BRAF inhibitors, including two previously reported cases of granuloma annulare (GA) eruptions associated with vemurafenib therapy. Both of these patients were being treated for metastatic melanoma. In this report, we describe the case of a 71-year-old man who developed classic GA lesions while being treated with vemurafenib monotherapy for nonmelanoma cancer, specifically metastatic lung adenocarcinoma positive for BRAF V600 mutation.
J Drugs Dermatol. 2017;16(10):1050-1052.
.Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/efeitos adversos , Granuloma Anular/induzido quimicamente , Indóis/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Sulfonamidas/efeitos adversos , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Antineoplásicos/administração & dosagem , Humanos , Indóis/administração & dosagem , Neoplasias Pulmonares/patologia , Masculino , Mutação , Metástase Neoplásica , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/administração & dosagem , VemurafenibRESUMO
BACKGROUND: While clinical outcomes following immunotherapy have shown an association with tumor mutation load using whole exome sequencing (WES), its clinical applicability is currently limited by cost and bioinformatics requirements. METHODS: We developed a method to accurately derive the predicted total mutation load (PTML) within individual tumors from a small set of genes that can be used in clinical next generation sequencing (NGS) panels. PTML was derived from the actual total mutation load (ATML) of 575 distinct melanoma and lung cancer samples and validated using independent melanoma (n = 312) and lung cancer (n = 217) cohorts. The correlation of PTML status with clinical outcome, following distinct immunotherapies, was assessed using the Kaplan-Meier method. RESULTS: PTML (derived from 170 genes) was highly correlated with ATML in cutaneous melanoma and lung adenocarcinoma validation cohorts (R2 = 0.73 and R2 = 0.82, respectively). PTML was strongly associated with clinical outcome to ipilimumab (anti-CTLA-4, three cohorts) and adoptive T-cell therapy (1 cohort) clinical outcome in melanoma. Clinical benefit from pembrolizumab (anti-PD-1) in lung cancer was also shown to significantly correlate with PTML status (log rank P value < 0.05 in all cohorts). CONCLUSIONS: The approach of using small NGS gene panels, already applied to guide employment of targeted therapies, may have utility in the personalized use of immunotherapy in cancer.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/terapia , Imunoterapia/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Melanoma/genética , Melanoma/terapia , Mutação , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Adenocarcinoma/imunologia , Adenocarcinoma de Pulmão , Algoritmos , Anticorpos Monoclonais/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Estudos de Coortes , Exoma , Feminino , Humanos , Imunoterapia Adotiva/métodos , Ipilimumab , Neoplasias Pulmonares/imunologia , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/imunologia , Linfócitos T/imunologia , Linfócitos T/transplante , Carga Tumoral/genética , Melanoma Maligno CutâneoRESUMO
BACKGROUND: SMARCB1 (INI1/BAF47/SNF5) encodes a part of a multiprotein complex that regulates gene expression through chromatin remodeling. SMARCB1 expression is lost or downregulated in multiple human tumors, including epithelioid sarcoma, meningioma and rhabdoid tumors of the brain, soft tissue and kidney. METHODS: A 46-gene or 50-gene next-generation sequencing AmpliSeq Cancer Panel (Life Technologies; San Francisco, CA, USA) was applied to â¼1400 primary or metastatic melanoma tissues. RESULTS: We identified eight cases of melanoma harboring mutations in SMARCB1. Immunohistochemistry demonstrated preservation of SMARCB1 protein expression in all cases. SMARCB1 mutations occurred together with TP53 mutations in five of the eight cases, suggesting a functional relationship between these tumor suppressors in melanoma. CONCLUSIONS: Because single-base substitutions in SMARCB1 occur in a small subset of melanomas and do not affect SMARCB1 protein expression, such mutations would only be discovered by sequencing approaches. Our findings highlight the potential for next-generation sequencing platforms to identify mutations unexpected for melanoma that may contribute to its oncogenic potential. Though rare, the identification of SMARCB1 mutations adds to the growing literature regarding the role of epigenetic control mechanisms in melanoma progression and therapeutic resistance and provide a rationale for strategies targeting such alterations (via chromatin remodeling agents) in clinical trials.
Assuntos
Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Melanoma/genética , Mutação , Análise de Sequência de DNA/métodos , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Regulação para Baixo , Epigênese Genética , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Proteína SMARCB1 , Proteína Supressora de Tumor p53/genéticaRESUMO
A 59-year-old male presented with 1 month of progressive dyspnea, 30-lb weight loss, and skin changes on the digits of the hands. In the 4 weeks prior to admission, he was admitted and treated twice for pneumonia at another hospital and received intravenous (IV) vancomycin, ceftriaxone, and azithromycin for a total of 10 days. After admission, he underwent computed tomography imaging of chest, which revealed findings suggestive of interstitial lung disease but given the fact that infection was not ruled out, empiric antibiotics were initiated. The skin lesions on the fingers were felt to be consistent with Gottron's papules, and his overall constellation of findings were felt to be consistent with dermatomyositis (DM). Over the following 3 days, he developed diffuse, violaceous skin lesions, elevation of liver transaminases, and severe thrombocytopenia. The skin lesions progressed to epidermal necrosis. He developed erosions of the oral mucosa and scrotum. Before skin biopsy results were finalized, IV immunoglobulin and IV dexamethasone were started empirically for suspected DM and immune-mediated thrombocytopenia. His laboratory abnormalities normalized within a week. Biopsy results of the skin were consistent with Stevens-Johnson syndrome (SJS). Autoantibody test for anti-MDA5 were positive, confirming a diagnosis of anti-MDA5 associated DM. Subsequent development of SJS was likely due to antibiotic exposure in the preceding month. Simultaneous development of anti-MDA5 DM and SJS raises the question of a link between the 2 conditions. To our knowledge, this is the first reported association of these 2 conditions reported in the literature.
Assuntos
Autoanticorpos/imunologia , Dermatomiosite/imunologia , Helicase IFIH1 Induzida por Interferon/imunologia , Síndrome de Stevens-Johnson/etiologia , Trombocitopenia/etiologia , Autoanticorpos/sangue , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Dexametasona/administração & dosagem , Humanos , Imunoglobulinas Intravenosas , Masculino , Pessoa de Meia-Idade , Pele/patologia , Síndrome de Stevens-Johnson/patologia , Trombocitopenia/patologiaRESUMO
Lupus panniculitis (LP), also referred to as lupus erythematosus profundus (LEP), is a chronic recurrent inflammation condition of the subcutaneous fat. It occurs in 1 to 3% of patients with systemic lupus erythematosus (SLE) and in 10% of patients with discoid lupus erythematosus (DLE), but can also occur as an entity of its own. Patients with lupus panniculitis usually present with persistent, often tender and painful skin lesions, or subcutaneous nodules, that range from 1 to 5â¯cm in diameter. The overlying skin may appear erythematous; lesions may become ulcerated, and heal with atrophy, skin depression, dimpling and scaring. Lesions tend to resolve spontaneously and may follow a chronic course of remission and exacerbation that persists for months to years. The imaging features of facial LP are extremely scarce in the literature. We present a case of facial lupus panniculitis and describe the associated characteristic ultrasound, CT, and MR imaging findings along with histopathologic correlation.
Assuntos
Dermatoses Faciais/patologia , Lúpus Eritematoso Discoide/patologia , Paniculite de Lúpus Eritematoso/patologia , Adulto , Dermatoses Faciais/diagnóstico por imagem , Feminino , Humanos , Lúpus Eritematoso Discoide/diagnóstico por imagem , Imageamento por Ressonância Magnética , Paniculite de Lúpus Eritematoso/diagnóstico por imagem , Pele/patologia , Tomografia Computadorizada por Raios XRESUMO
Extramammary Paget disease (EMPD) is a locally aggressive cutaneous malignancy that usually arises in anogenital or axillary skin. Immune checkpoint inhibitors targeting programmed cell death receptor (PD-1) and/or its ligand (PD-L1) are approved for the treatment of several types of cancer, and response to these generally correlates with increased PD-L1 expression by tumor cells. The expression of PD-L1 and composition and density of the tumor-associated immune infiltrate in EMPD have been little studied. To determine whether EMPD might be amenable to immune checkpoint blockade, we analyzed the expression of PD-1 and PD-L1 and the composition and density of the tumor-associated immune infiltrate in EMPD and evaluated associations between biomarker expression and clinicopathologic parameters. Twenty-one EMPD tumors were evaluated for tumor cell PD-L1 expression and for relative expression and distribution of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate by using a combination of visual and image analysis (Aperio ImageScope). In addition, PD-L1 expression was assessed in 10 cases of mammary Paget disease (MPD). In EMPD cases, PD-L1 was expressed by tumor cells (3/21; 14%) and the tumor-associated immune infiltrate (15/21; 71%), and PD-1 was expressed by the tumor-associated immune infiltrate in all cases analyzed (18/18). However, PD-L1 expression by EMPD tumor cells did not correlate with the density of CD3-, CD8-, or PD-1-positive cells in the tumor-associated immune infiltrate or other clinicopathologic parameters. Furthermore, the density of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate did not correlate with any clinicopathologic parameters evaluated with the exception that CD3 positive values were significantly higher in patients who were still alive (median, 1310 cells/mm2; range, 543-2115;) than in those who died (median, 611 cells/mm2; range, 481-908; p = 0.049). In all MPD cases, PD-L1 was absent in tumor cells but present in the tumor-associated immune infiltrate, and PD-L1 expression in lymphocytes was lower in patients with HER2/neu-positive than in those with HER2/neu-negative disease (p = 0.07). Our findings raise the possibility of therapeutic targeting of the PD-1/PD-L1 axis in EMPD.
RESUMO
A relatively newer class of chemotherapy agents, known as the epidermal growth factor receptor inhibitors (EGF-RIs), is being used to treat advanced stages of solid tumors. Acneiform eruptions are a frequent adverse effect and one which has been associated with increased survival in some studies. We describe 3 patients who presented shortly after initiation of EGF-RI therapy. Characteristics included an absence of comedones, facial and truncal involvement, and a perifollicular lymphoneutrophilic infiltrate detected on biopsy. Lesion counts were reduced with topical adapalene and oral tetracyclines in two patients. Patient 3 had dramatic clearance with low-dose isotretinoin (20 mg daily) until completion of EGF-RI therapy. Acneiform eruptions are a common adverse reaction to EGF-RI therapy and can be treated with traditional acne therapy. This should not be considered a drug hypersensitivity eruption or allergy, and patients should continue therapy. For patients with severe eruptions, oral isotretinoin is a consideration.
Assuntos
Acne Vulgar/induzido quimicamente , Antineoplásicos/efeitos adversos , Receptores ErbB/antagonistas & inibidores , Acne Vulgar/tratamento farmacológico , Acne Vulgar/patologia , Adapaleno , Administração Oral , Administração Tópica , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Relação Dose-Resposta a Droga , Humanos , Isotretinoína/administração & dosagem , Isotretinoína/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Minociclina/administração & dosagem , Minociclina/uso terapêutico , Naftalenos/administração & dosagem , Naftalenos/uso terapêuticoRESUMO
Capsular nevi (CN) are clusters of benign melanocytes situated in the capsule of lymph nodes and occur in up to 20% of lympadenectomy specimens. The molecular profile of CN in relation to prognostic parameters in patients with primary cutaneous melanoma (PCM) has not been previously investigated. We assessed BRAF V600E mutation by immunohistochemistry (IHC) in the CN of sentinel lymph nodes (SLN) in PCM patients and correlated the findings with demographic characteristics, PCM histopathologic and molecular features, and clinical outcome parameters. Seventy-eight cases of CN involving SLN of PCM patients were evaluated for BRAF V600E mutation by IHC. The results were correlated with patient demographics, PCM histopathologic and molecular features, and outcome measures. Thirty-six (46%) of 78 CN cases expressed BRAF V600E mutation by IHC. Nineteen (53%) of those BRAF-positive CN cases were from patients with at least American Joint Committee on Cancer stage II melanoma, whereas 62% of BRAF-negative CN cases (26/42) were from patients with stage I melanoma (P = .013). Twelve (33%) of the 36 BRAF-positive CN cases had metastatic melanoma involving lymph nodes, compared with 14% (6/42) of BRAF-negative CN cases (P = .061). CN mutation status was not associated with patient demographics, histopathologic or molecular features of the PCM, or survival outcomes. A high percentage of CN identified in the SLN of patients with PCM harbor BRAF V600E mutation. Positive mutation was associated with adverse clinicopathological parameters, specifically increased tumor stage and lymph node metastasis. These findings suggest that BRAF V600E mutation in CN of SLN may be useful as an adverse predictive biomarker in patients with melanoma.
Assuntos
Biomarcadores Tumorais/genética , Linfonodos/patologia , Melanócitos/patologia , Melanoma/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Melanoma/enzimologia , Melanoma/secundário , Melanoma/terapia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Valor Preditivo dos Testes , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Adulto JovemRESUMO
Somatic copy number alterations (SCNAs) affecting oncogenic drivers have a firmly established role in promoting cancer. However, no agreed-upon standard exists for calling locus-specific amplifications and deletions in each patient sample. Here, we report the correlative analysis of copy number amplitude and length with gene expression across 6,109 samples from The Cancer Genome Atlas (TCGA) dataset across 16 cancer types. Using specificity, sensitivity, and precision-based scores, we assigned optimized amplitude and length cutoffs for nine recurrent SCNAs affecting known oncogenic drivers, using mRNA expression as a functional readout. These cutoffs captured the majority of SCNA-driven, highly-expression-altered samples. The majority of oncogenes required only amplitude cutoffs, as high amplitude samples were almost invariably focal; however, CDKN2A and PTEN uniquely required both amplitude and length cutoffs as primary predictors. For PTEN, these extended to downstream AKT activation. In contrast, SCNA genes located peri-telomerically or in fragile sites showed poor expression-copy number correlations. Overall, our analyses identify optimized amplitude and length cutoffs as efficient predictors of gene expression changes for specific oncogenic SCNAs, yet warn against one-size-fits-all interpretations across all loci. Our results have implications for cancer data analyses and the clinic, where copy number and mutation data are increasingly used to personalize cancer therapy.
Assuntos
Carcinogênese/genética , Variações do Número de Cópias de DNA , Regulação Neoplásica da Expressão Gênica , Loci Gênicos , Neoplasias/genética , Oncogenes , Proteínas Supressoras de Tumor/genética , Bases de Dados Genéticas , Dosagem de Genes , Humanos , Curva ROCRESUMO
The management of melanoma has evolved owing to improved understanding of its molecular drivers. To augment the current understanding of the prevalence, patterns, and associations of mutations in this disease, the results of clinical testing of 699 advanced melanoma patients using a pan-cancer next-generation sequencing (NGS) panel of hotspot regions in 46 genes were reviewed. Mutations were identified in 43 of the 46 genes on the panel. The most common mutations were BRAFV600 (36%), NRAS (21%), TP53 (16%), BRAFNon-V600 (6%), and KIT (4%). Approximately one-third of melanomas had >1 mutation detected, and the number of mutations per tumor was associated with melanoma subtype. Concurrent TP53 mutations were the most frequent events in tumors with BRAFV600 and NRAS mutations. Melanomas with BRAFNon-V600mutations frequently harbored concurrent NRAS mutations (18%), which were rare in tumors with BRAFV600 mutations (1.6%). The prevalence of BRAFV600 and KIT mutations were significantly associated with melanoma subtypes, and BRAFV600 and TP53 mutations were significantly associated with cutaneous primary tumor location. Multiple potential therapeutic targets were identified in metastatic unknown primary and cutaneous melanomas that lacked BRAFV600 and NRAS mutations. These results enrich our understanding of the patterns and clinical associations of oncogenic mutations in melanoma.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Melanoma/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , GTP Fosfo-Hidrolases/genética , Genes p53 , Humanos , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas c-kit/genéticaRESUMO
PURPOSE: Loss of function of PTEN is a frequent event in melanoma, particularly in tumors with BRAF(V600) mutations. The prevalence, pathologic features, and clinical outcomes associated with PTEN loss in patients with stage IIIB/C melanoma were interrogated to improve our understanding of the clinical significance of this molecular event. EXPERIMENTAL DESIGN: Archival tissue from lymphadenectomy specimens among patients (n = 136) with stage IIIB or IIIC melanoma was assessed by DNA sequencing for activating BRAF and NRAS mutations, and by immunohistochemistry for the expression of PTEN protein. Associations of these molecular aberrations with demographics, tumor characteristics, and clinical outcomes were determined. RESULTS: The prevalence of BRAF(V600) mutations (40% overall), NRAS mutations (10%), and PTEN loss (25%) did not vary by pathologic substage. BRAF/NRAS mutation status did not correlate with distant disease-free survival (DDFS) or overall survival (OS). Complete loss of PTEN expression correlated with shorter OS but not DDFS. When stratified by specific sites of distant metastasis, PTEN loss was associated with significantly shorter time to melanoma brain metastasis (MBM), but not to liver, lung, or bone metastasis. Analysis of PTEN in mutationally defined subsets showed that PTEN loss was significantly associated with OS and time to MBM in patients with BRAF(V600) mutations. CONCLUSIONS: Loss of PTEN protein expression correlates significantly with decreased OS and time to MBM in stage IIIB/C melanoma patients with BRAF(V600) mutations. The findings add to evidence supporting a significant role for PTEN loss and the PI3K-AKT pathway in melanoma.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Melanoma/genética , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Mutação/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Adulto JovemAssuntos
Antineoplásicos/uso terapêutico , Melanoma/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Cutâneas/genética , Institutos de Câncer , Estudos de Coortes , Dasatinibe/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Mesilato de Imatinib/uso terapêutico , Masculino , Melanoma/imunologia , Terapia de Alvo Molecular/métodos , Mutação , Prognóstico , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Neoplasias Cutâneas/imunologia , Análise de Sobrevida , Texas , Resultado do TratamentoRESUMO
We present a 62-year-old male with a recurrent cyst in the left posterior chest. MRI demonstrated a fluid-filled cavity measuring 23 cm in length and 11 cm in width. The cyst was aspirated demonstrating clear serous fluid. However, the cyst returned and he was referred to us for further treatment. The cyst was excised through a minimally invasive approach using a combination of blunt and electrocautery dissection. The cystic lesion was circumferentially freed from the trapezius muscle and cervical structures. Pathologic examination revealed a benign, fibrous-walled cyst without a true epithelial lining. There are no published reports of a deep thoracic wall cyst resembling this case in terms of histology or location. This patient is free of recurrence 1 year later.
RESUMO
Triple-negative breast cancer comprises 10% to 15% of newly diagnosed breast cancer and lacks expression of the estrogen, progesterone, and human epidermal growth factor receptor 2/neu receptors. Many such tumors are basal like, a molecular intrinsic subtype of breast cancer associated with poor clinical outcomes. Patients with early-stage basal-like triple-negative breast cancer are at a high risk for relapse and may, therefore, benefit from novel therapies, including immunotherapy. MUC1 is a tumor antigen expressed on adenocarcinomas and represents an ideal target for MUC1-based vaccination. We evaluated 52 cases of early-stage basal-like triple-negative breast cancer for MUC1 expression by immunohistochemistry. The intensity of staining was graded according to the intensity (negative [0], positive [1], or strongly positive [2]) and percentage (0%-100%) of tumor cells staining for MUC1. An overall score of 0 to 2.0 was calculated for each case by multiplying the intensity of staining by the percentage of tumor cells staining positively. Four staining patterns for MUC1 were identified: apical, cytoplasmic, membranous, and combination. Of the 52 cases of basal-like triple-negative breast cancers, 49 (94%) were positive for MUC1 expression. The mean score was 0.90 (range, 0-1.9). Cases were evenly distributed over this range, where most (67%) exhibited moderate to strong MUC1 expression (score, 0.5-1.90), 27% demonstrated weak MUC1 expression, and 6% lacked MUC1 expression. There was a significant difference in MUC1 score and percent MUC1+ cells in favor of the combination pattern. This study indicates that a large proportion of early-stage basal-like triple-negative breast cancer expresses MUC1 and provides a rationale for MUC1-based immunotherapy in this high-risk patient cohort.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias da Mama/metabolismo , Mucina-1/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Diagnóstico Precoce , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
Metastatic Crohn disease is a rare cutaneous disorder characterized by noncaseating, granulomatous skin lesions present at sites anatomically separate from the gastrointestinal tract. It is the least common dermatologic manifestation of Crohn disease, and the differential diagnosis includes numerous similarly appearing, granulomatous skin entities. Males and females appear to be equally affected, and children tend to present with clinical lesions different from those of adults. An integration of clinical information, microscopic findings, and ancillary studies is necessary to accurately diagnose this rare cutaneous disease. Our objective is to review the clinical features, histopathologic characteristics, suggested pathogenesis, differential diagnosis, and current therapeutic options of metastatic Crohn disease.