RESUMEN
Colorectal cancer (CRC) is a leading cause of morbidity and mortality and alterations in mismatch repair (MMR) genes, leading to absent protein (negative) expression, are responsible for approximately 20% of CRC cases. Immunohistochemistry is a tool for prescreening of MMR protein expression in CRC but the literature on its use on Hispanics is scarce. However, Hispanics represent the second leading ethnicity in the United States (US) and CRC is a public health burden in this group. Our objectives were to determine the frequency of MMR protein-negative CRC and to evaluate its association with clinical and pathological characteristics among Hispanics from Puerto Rico, for the first time to our knowledge. A retrospective observational study of unselected CRC patients from the Puerto Rico Medical Center from 2001 to 2005 was done. MLH1 and MSH2, the most commonly altered MMR genes, protein expression was evaluated using immunohistochemistry, with microsatellite instability (MSI) and BRAF gene analyses in the absence of MLH1 protein expression. One-hundred sixty-four CRC patients were evaluated: the overall MMR protein-negative frequency was 4.3%, with 0.6% frequency of co-occurrence of MLH1-protein negative expression, MSI-high, and normal BRAF gene. MMR protein-negative expression was associated with proximal colon location (P = 0.02) and poor histological tumor differentiation (P = 0.001), but not with other characteristics. The frequency of MMR protein-negative CRC in Hispanics from Puerto Rico was lower than reported in other populations. This finding may explain the lower CRC incidence rate among US Hispanics as compared to US non-Hispanic whites and blacks.
Asunto(s)
Neoplasias Colorrectales/genética , Reparación de la Incompatibilidad de ADN/genética , Proteína 2 Homóloga a MutS/genética , Proteínas Adaptadoras Transductoras de Señales/fisiología , Neoplasias Colorrectales/metabolismo , Reparación del ADN , Hispánicos o Latinos/genética , Humanos , Proteína 2 Homóloga a MutS/metabolismo , Puerto Rico/epidemiología , Estados Unidos/etnologíaRESUMEN
BACKGROUND: Muir-Torre Syndrome (MTS) is a rare autosomal-dominant disorder characterized by the predisposition to both sebaceous neoplasm and internal malignancies. MTS-associated sebaceous neoplasms reveal mutations in DNA mismatch repair (MMR) genes and microsatellite instability. A significant part of MTS patients represents a phenotypic variant, the hereditary nonpolyposis colorectal cancer (HNPCC). A strong correlation between microsatellite instability and immunostaining has been demonstrated. The early recognition of sebaceous neoplasm as part of MTS, and their differentiation from sporadic sebaceous neoplasm may have an important application in a clinical setting. The absence of MLH-1 or MSH-2 expression by immunostaining identifies tumors with mismatch repair deficiency. OBJECTIVES: Our aim is to determine whether an immunohistochemical approach, targeting DNA repair proteins MSH-2 and MLH-1 in MTS-related sebaceous neoplasm and their sporadic counterparts, can be used for their identification. METHODS: We examined 15 sebaceous neoplasms (including 6 internal malignancy- associated sebaceous neoplasms and 8 sporadic sebaceous neoplasms) from 11 patients for the expression of MSH-2 and MLH-1 by immunohistochemistry. RESULTS: Four of 5 internal malignancy-associated sebaceous neoplasms showed loss of expression of MSH-2 or MLH-1. Correlation of the immunostaining pattern of the sebaceous neoplasms and the patients' positive history of colon carcinoma was 80%. Seven of 8 sporadic sebaceous neoplasms showed a positive expression of MSH-2 and MLH-1. The prevalence for loss of expression of MMR proteins in sebaceous neoplasms was 38.5%. MMR immunostaining had 87.5% specificity and 80% sensitivity. LIMITATIONS: This study is limited by a small sample size, and by bias selection due to the use of non nationwide data-base as the resource of cases. CONCLUSIONS: Our findings demonstrate that immunohistochemical testing for internal malignancy-associated sebaceous neoplasms is a practical approach to confirm a suspected inherited MMR gene defect, and an accurate method to distinguish between sporadic and MTS-associated sebaceous lesions.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Síndrome de Muir-Torre/metabolismo , Proteína 2 Homóloga a MutS/biosíntesis , Proteínas Nucleares/biosíntesis , Neoplasias de las Glándulas Sebáceas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutLRESUMEN
Crohn's disease is an inflammatory bowel disease characterized by remissions and exacerbations. Immunosuppressants are frequently used to induce and maintain remission in these patients. The use of the immunomodulator azathioprine has been associated to malignancies. Chordomas are rare, locally aggressive tumors arising from remnants of the notochord. A specific trigger for this tumor has not been identified and association to any medication has not been reported. The purpose of this report is to present the first case reported in the literature of Crohn's disease associated to a chordoma. The patient to be presented was on azathioprine therapy, among other medications. A review of literature revealed that Crohn's disease and chordoma have abnormalities in chromosomes 1 and 10. Inflammatory bowel disease and chordoma also have abnormalities in chromosomal regions 1p, 3p, and 7q. Despite these findings, a direct genetic relationship between these diseases is speculative.
Asunto(s)
Cordoma/complicaciones , Enfermedad de Crohn/complicaciones , Neoplasias de la Base del Cráneo/complicaciones , Adulto , Cordoma/diagnóstico , Cordoma/cirugía , Colon/diagnóstico por imagen , Colon/patología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/patología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Imagen por Resonancia Magnética , Procedimientos Neuroquirúrgicos , Neoplasias de la Base del Cráneo/diagnóstico , Neoplasias de la Base del Cráneo/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the response rate of Hispanics with chronic hepatitis C to combination therapy of interferon alfa-2b plus ribavirin and to assess its adverse events. BACKGROUND: Hepatitis C virus may lead to chronic infection and multiple complications. Response to combination therapy of interferon plus ribavirin has been studied in many populations. African Americans have been found to have a lower response rate than Caucasians. However, little data exist for Hispanics. METHODS: Hispanic patients from Puerto Rico with chronic hepatitis C were eligible for the study between November 1997 and February 2000. The Institutional Review Boards of the participating institutions approved the study. Written informed consents were obtained. Combination therapy was given for 48 weeks and patients were followed for 24 weeks after treatment. Analysis of response to therapy was performed in an intention-to-treat basis. RESULTS: The most frequent adverse event was anemia (89%), associated to ribavirin. Sustained response was 23% for naive patients, 45% for relapsers, and 8% for non-responders to previous interferon monotherapy (p < 0.001). Data to analyze response was not available in 27% of patients. Hispanic patients had a low response rate to combination therapy. CONCLUSIONS: Response rates to combination therapy for Hispanic naive and previously non-responder patients are lower than in other reported populations. This may be due to a high prevalence of genotype 1 in Puerto Rico, which is associated to poor response. The higher response rate of relapsers, similar to those reported previously, was expected since these patients showed a previous response to interferon monotherapy. Ethnic factors may play a role in the response to therapy and should be further studied to determine proper treatment strategies for this population.