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1.
Can J Urol ; 15(3): 4112-4, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18570720

RESUMO

The interstitial cells of Cajal have been identified in locations beyond the gastrointestinal tract, including the prostate, uterus and bladder. Indeed, there are reports of primary gastrointestinal stromal tumor (GIST) arising from each of these sites. We report the case of a 72-year old male who presented with benign prostatic hypertrophy and was diagnosed on retropubic prostatectomy as having a GIST. While the initial clinical and radiologic impression was that of a primary prostatic GIST, subsequent imaging ultimately revealed a small rectal extension as the source of the lesion. The purpose of our report is to highlight the need to assiduously rule-out gastrointestinal sources of GIST prior to making the diagnosis of primary prostatic GIST.


Assuntos
Tumores do Estroma Gastrointestinal/diagnóstico , Neoplasias da Próstata/diagnóstico , Neoplasias Retais/diagnóstico , Idoso , Diagnóstico Diferencial , Tumores do Estroma Gastrointestinal/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Próstata/patologia , Neoplasias Retais/patologia
2.
Clin Cancer Res ; 11(19 Pt 1): 6853-61, 2005 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-16203774

RESUMO

PURPOSE: Newfoundland has one of the highest rates of colorectal cancer in North America. The most common hereditary form of colorectal cancer is hereditary nonpolyposis colorectal cancer caused by mutations in genes involved in mismatch repair. Our purpose was to determine the proportion of hereditary colorectal cancer and to determine the genetic basis of disease in both population and clinically referred cohorts from Newfoundland. EXPERIMENTAL DESIGN: Seventy-eight colorectal cancer patients were accrued over a 2-year period from the Avalon Peninsula of Newfoundland. We also examined 31 hereditary nonpolyposis colorectal cancer-like families, which had been referred to the Provincial Medical Genetics Program. Tumors from probands were tested by immunohistochemistry for deficiencies in MLH1, MSH2, and MSH6 proteins and tested for DNA microsatellite instability. Mutation analyses of MLH1, MSH2, and MSH6 were undertaken by direct sequencing and an assay to detect deletions, amplifications, and rearrangements in MSH2 and MLH1. RESULTS: We identified eight population-based families that fulfill the Amsterdam I or II criteria, 4 (50%) of which seem to have hereditary cancer not attributable to the most commonly mutated mismatch repair genes. In addition, in 16 of 21 (76%) referred families fulfilling Amsterdam I or II criteria, no mutations were found in the three most commonly altered mismatch repair genes, and tumor analyses corroborated these findings. CONCLUSIONS: It seems that strong and novel genetic causes of hereditary colorectal cancer are responsible for a high proportion of colorectal cancer in this population. Conditions are suitable for the identification of these genes by linkage studies of large Newfoundland cancer families.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Ligação Genética , Predisposição Genética para Doença , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Fatores Etários , Idoso , Pareamento Incorreto de Bases , Proteínas de Transporte/genética , Estudos de Coortes , Neoplasias Colorretais Hereditárias sem Polipose/genética , Metilação de DNA , Reparo do DNA , Proteínas de Ligação a DNA/genética , Feminino , Variação Genética , Humanos , Imuno-Histoquímica , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Modelos Genéticos , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Mutação , Terra Nova e Labrador , Proteínas Nucleares/genética , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Fatores de Tempo
3.
Acta Cytol ; 47(6): 979-84, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14674066

RESUMO

OBJECTIVE: To determine whether immunocytochemistry (ICC) for HER2 on ThinPrep (TP)-processed breast fine needle aspiration biopsies (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) is comparable to the findings of immunohistochemistry on corresponding surgically removed tissue. STUDY DESIGN: Immunostaining was performed on 63 malignant breast fine needle aspirates and compared to immunostaining on paraffin sections (PSs) from the subsequent biopsies. The HercepTest (Dako, Carpinteria, California, U.S.A.) and TAB250 antibodies were utilized. Cases in which the TP and paraffin HER2 results did not correlate were further assessed for gene amplification by differential polymerase chain reaction (dPCR). RESULTS: HER2 overexpression was found in 9 of the 63 cases (14%). TAB250 had higher specificity on PS versus TP (P = .008), and TAB250 had higher specificity on PS versus the HercepTest on PS and TP (P = .004 and .0001, respectively). CONCLUSION: HER2 immunostaining with both the HercepTest and TAB250 on TP is unreliable due to low specificity (72% and 83% for HercepTest and TAB250, respectively). However, both antibodies have high sensitivity (89% and 100%, respectively); suggesting that this method may have some utility as a preliminary screening test for HER2 status. Negative HER2 staining by ICC is highly predictive of the absence of HER2 overexpression, whereas positive HER2 staining on TP would require further validation by either dPCR of fluorescence in situ hybridization.


Assuntos
Biópsia por Agulha Fina/normas , Neoplasias da Mama/patologia , Carcinoma/patologia , Imuno-Histoquímica/normas , Receptor ErbB-2/análise , Anticorpos , Biópsia por Agulha Fina/estatística & dados numéricos , Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Feminino , Humanos , Imuno-Histoquímica/estatística & dados numéricos , Variações Dependentes do Observador , Patologia Cirúrgica/normas , Patologia Cirúrgica/estatística & dados numéricos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Inclusão do Tecido/normas
4.
PLoS One ; 8(12): e82173, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24349213

RESUMO

Here, we demonstrated the differentiation potential of murine muscle-derived stem/progenitor cells (MDSPCs) toward myogenic, neuronal, and glial lineages. MDSPCs, following transplantation into a critical-sized sciatic nerve defect in mice, showed full regeneration with complete functional recovery of the injured peripheral nerve at 6 weeks post-implantation. However, several weeks after regeneration of the sciatic nerve, neoplastic growths were observed. The resulting tumors were malignant peripheral nerve sheath tumors (MPNSTs) with rhabdomyoblastic differentiation, expressing myogenic, neurogenic, and glial markers, common markers of human malignant triton tumors (MTTs). No signs of tumorigenesis were observed 17 weeks post-implantation of MDSPCs into the gastrocnemius muscles of dystrophic/mdx mice, or 1 year following subcutaneous or intravenous injection. While MDSPCs were not oncogenic in nature, the neoplasias were composed almost entirely of donor cells. Furthermore, cells isolated from the tumors were serially transplantable, generating tumors when reimplanted into mice. However, this transformation could be abrogated by differentiation of the cells toward the neurogenic lineage prior to implantation. These results establish that MDSPCs participated in the regeneration of the injured peripheral nerve but transformed in a microenvironment- and time-dependent manner, when they likely received concomitant neurogenic and myogenic differentiation signals. This microenvironment-specific transformation provides a useful mouse model for human MTTs and potentially some insight into the origins of this disease.


Assuntos
Células-Tronco Adultas/patologia , Transformação Celular Neoplásica/patologia , Microambiente Celular , Neurilemoma/patologia , Adulto , Animais , Diferenciação Celular , Linhagem da Célula , Separação Celular , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular , Músculo Esquelético/patologia , Regeneração Nervosa , Neurilemoma/fisiopatologia , Neurogênese , Neuroglia/citologia , Recuperação de Função Fisiológica , Células de Schwann/citologia , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia , Nicho de Células-Tronco , Transplante de Células-Tronco
5.
Gastroenterology ; 133(1): 48-56, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17631130

RESUMO

BACKGROUND & AIMS: The revised Bethesda guidelines for Lynch syndrome recommend microsatellite instability (MSI) testing all colorectal cancers in patients diagnosed before age 50 years and colorectal cancers diagnosed in patients between ages 50 and 59 years with particular pathology features. Our aim was to identify pathology and other features that independently predict high MSI (MSI-H). METHODS: Archival tissue from 1098 population-based colorectal cancers diagnosed before age 60 years was tested for MSI. Pathology features, site, and age at diagnosis were obtained. Multiple logistic regression was performed to determine the predictive value of each feature, as measured by an odds ratio (OR), from which a scoring system (MsPath) was developed to estimate the probability a colorectal cancer is MSI-H. RESULTS: Fifteen percent of tumors (162) were MSI-H. Independent predictors were tumor-infiltrating lymphocytes (OR, 9.1; 95% confidence interval [CI], 5.9-14.1), proximal subsite (OR, 4.7; 95% CI, 3.1-7.3), mucinous histology (OR, 2.8; 95% CI, 1.7-4.8), poor differentiation (OR, 1.9; 95% CI, 1.2-3.1), Crohn's-like reaction (OR, 1.9; 95% CI, 1.2-2.9), and diagnosis before age 50 years (OR, 1.9; 95% CI, 1.3-2.9). MsPath score >or=1.0 had a sensitivity of 93% and a specificity of 55% for MSI-H. CONCLUSIONS: The probability an individual colorectal cancer is MSI-H is predicted well by the MsPath score. There is little value in testing for DNA mismatch repair loss in tumors, or for germline mismatch repair mutations, for colorectal cancers diagnosed in patients before age 60 years with an MSPath score <1 (approximately 50%). Pathology can identify almost all MSI-H colorectal cancers diagnosed before age 60 years.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Gastroenterologia/normas , Instabilidade de Microssatélites , Guias de Prática Clínica como Assunto/normas , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , Oncologia/normas , Pessoa de Meia-Idade , Modelos Genéticos , Valor Preditivo dos Testes , Probabilidade , Reprodutibilidade dos Testes
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