Amplifications of AURKA and AURKB in a Burkitt lymphoma immunodeficiency-associated type: a case report

ABSTRACT In equatorial Brazil, the association of Burkitt lymphoma and Epstein-Barr virus manifests at high rates. Here, we report, for the first time, amplifications of aurora kinase genes (AURKA/B) in a patient with a history of periodontal abscess and the presence of a remaining nodule, diagnosed with Burkitt lymphoma and Epstein-Barr virus, and /HIV positive. The patient was a 38-year-old man who presented with a 2-week-old severe jaw pain and a 3-day-old severe bilateral headache. He had a history of human papilloma virus. Interphase FISH analysis showed AURKA and AURKB amplification. The patient's condition worsened, progressing to death a month after the initial care. Changes in the MYCC and AURKA pathways are directly associated with genomic instability. Thus, MYCC rearrangements and higher expression of AURKA/B may be associated with therapy resistance, highlighting the importance of AURKA/B evaluation in Burkitt lymphoma.

Immunoexpression of PD-L1, CD4+ and CD8+ cell infiltrates and tumor-infiltrating lymphocytes (TILs) in the microenvironment of actinic cheilitis and lower lip squamous cell carcinoma

Abstract Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient. Objective: Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics. Methodology: This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry. Results: There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells. Conclusion: Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs.

Sarcoma fibromixoide de baixo grau em região paratesticular: um relato de caso / Low-grade fibromyxoid sarcoma in paratesticular area: a case report

Objetivos: relatar um caso raro de sarcoma fibromixoide de baixo grau (SFMBG) em uma localização incomum de modo a reforçar aspectos histopatológicos e imunoistoquímicos relevantes para o reconhecimento desta entidade e o adequado diagnóstico diferencial de massas paratesticulares. Relato de caso: homem de 20 anos, com massa escrotal à direita, cuja análise histopatológica demonstrou a presença de tecido fibroso com áreas mixoides e predominância de células fusiformes. A imunoistoquímica foi positiva para vimentina, com índice de Ki67 de 2%, e negativa para S100, CD-34, beta-catenina, desmina e miogenina. Conclusões: caso raro de SFMBG na região paratesticular que reforça a importância da histopatologia e da imunoistoquímica no diagnóstico desse tumor. Apesar da característica histológica benigna, o SFMBG apresenta altas taxas de recorrência e metástases, sendo essencial o seguimento do paciente.

Objectives: to report a rare case of low-grade fibromyxoid sarcoma (LGFMS) in an unusual location in order to reinforce histopathological and immunohistochemical aspects relevant to the recognition of this entity and the adequate differential diagnosis of paratesticular masses. Case report: 20-year-old man, with a right scrotal mass and histopathological analysis showing the presence of fibrous tissue with myxoid areas and a predominance of spindle cells. Immunohistochemistry was positive for vimentin, with a Ki67 index of 2%, and negative for S100, CD-34, beta-catenin, desmin and myogenin. Conclusions: rare case of LGFMS in the paratesticular region that reinforces the importance of histopathology and immunohistochemistry in the diagnosis of this tumor. Despite the benign histological characteristic, LGFMS has high rates of recurrence and metastasis, and patient follow-up is essential.

Gonadal differentiation during embryonic and fetal development of male New Zealand rabbits (Oryctolagus cuniculus) / Diferenciación gonadal durante el desarrollo embrionario y fetal de conejos machos neozelandeses (Oryctolagus cuniculus)

SUMMARY: The rabbit is considered an ideal animal model for studies that describe abnormalities in the testicles due to the similar morphogenetic mechanisms of sexual development and diseases commonly found in humans. The aim of this study was to determine the male sexual differentiation of the New Zealand rabbit (Oryctolagus cuniculus) through development. The gestational age was estimated and classified as 9, 12, 14, 16, 18, 20, 23 and 28 gestational days. The morphological and sexual determination were performed by histological analysis of the reproductive tract in the embryos and fetuses (9-28 days) as well as by immunohistochemistry- Desert hedgehog-Dhh- (testis-specific protein on Y chromosome- 16, 20, 23 days and adult rabbits). Gonads were observed from the 14th day in an undifferentiated stage and with homogeneous aspect. Sexual differentiation was observed from the 16th day with presence of cells forming gonadal cords and Dhh+ cells in the gonadal parenchyma. From the 18th gestational day testicular cords were observed, which evolved into organized seminiferous tubules. The formation of the efferent ducts and ductus deferens and epididymis was observed on the 20th and 23rd days, respectively. The differentiation of the external genitalia occurred from the 23rd days from the anogenital distance and was identified to identify the penile structures. In summary, the features of the sexual differentiation were determined by observation of the Dhh+ protein in embryos from the 16th day to adulthood, and the morphological particularities observed from the 18th gestational day, determined by differentiation of the external genitalia from the 23rd day.

RESUMEN: El conejo se considera un modelo animal ideal para estudios que describen anomalías a nivel testícular debido a que presenta mecanismos morfogenéticos similares al desa- rrollo sexual y enfermedades que se encuentran comúnmente en los seres humanos. El objetivo de este estudio fue determinar la diferenciación sexual masculina del conejo de Nueva Zelanda (Oryctolagus cuniculus) a través del desarrollo. La edad gestacional se estimó y clasificó en 9, 12, 14, 16, 18, 20, 23 y 28 días gestacionales. La determinación morfológica y sexual se realizó mediante análisis histológico del tracto reproductivo en los embriones y fetos (9 - 28 días) así como mediante inmunohistoquímica -Desert hedgehog-Dhh- (proteína testicular específica en el cromosoma Y- 16, 20, 23 días y conejos adultos). Las gónadas se observaron a partir del día 14 en un estadio indiferenciado y con aspecto homogéneo. Se observó diferenciación sexual a partir del día 16 con presencia de células formadoras de cordones gonadales y células Dhh+ en el parénquima gonadal. A partir del día 18 de gestación se observaron cordones testiculares, que evolucionaron a túbulos seminíferos organizados. La formación de los conductos eferentes, deferentes y del epidídimo se observó a los 20 y 23 días, respectivamente. La diferenciación de los genitales externos ocurrió a partir del día 23 desde la distancia anogenital y se utilizó para identificar las estructuras del pene. En conclusión, las características de la diferenciación sexual se determinaron mediante la observación de la proteína Dhh en embriones desde el día 16 hasta la edad adulta, y las particularidades morfológicas observadas a partir del día 18 de gestación, determinadas por diferenciación de los genitales externos a partir del día 23.

Qualidade de vida em pacientes com insuficiência cardíaca: análise de três anos em um serviço especializado

Introdução. A insuficiência cardíaca (IC) apresenta elevada morbimortalidade, além de exercer grande impacto sobre a qualidade de vida (QV). O Minnesota Living with Heart Failure Questionnaire (MLHFQ) é um escore que avalia a QV dos pacientes portadores dessa síndrome, no qual uma maior pontuação reflete uma menor QV. Objetivo. Avaliar a QV dos pacientes com IC após três anos de seguimento em um serviço ambulatorial especializado de um hospital-escola. Métodos. Estudo unicêntrico, descritivo e prospectivo em que se aplicou o MLHFQ, de modo voluntário e sigiloso, a pacientes com IC com fração de ejeção reduzida acompanhados ambulatorialmente na clínica de IC. Foram analisados os resultados dos MLHFQ dos pacientes comparando-se o momento da inclusão no estudo, em 2014, e após o seguimento de três anos, em 2017/18. Resultados. Dos 76 pacientes inicialmente entrevistados, 74 (97,4%) responderam ao questionário e foram incluídos no estudo, em 2014. Após seguimento de três anos, 39,2% (29/74) dos pacientes responderam novamente ao questionário e em 59,8% (45/74) não se pôde aplicar o MLHFQ pela segunda vez (óbitos: 11; perda de acompanhamento no serviço: 21; não localizados: 13). O escore médio obtido pelo MLHFQ foi de 40,3 ± 21 pontos no momento da inclusão e 31,6 ± 23 pontos após três anos de acompanhamento no serviço (p=0,001). Conclusão. Observou-se baixa QV em pacientes com IC incluídos no estudo, havendo melhora significativa após três anos de acompanhamento no serviço especializado. As clínicas de IC podem aumentar expressivamente a QV dos pacientes portadores de IC, proporcionando potencial benefício prognóstico.

Background. Heart failure (HF) presents high morbidity and mortality, besides having great impact on quality of life (QoL). The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is a score that assesses the QoL of patients with this syndrome, in which the higher scores indicates lower QoL. Objective. To analyze the QoL of HF patients after three years of follow-up at the specialized outpatient service of a teaching hospital. Methods. Unicentric, descriptive, prospective study that voluntarily and confidentially applied MLHFQ in patients with HF with reduced ejection fraction followed at the HF clinic. The results of the patients MLHFQ compared at the time of inclusion in the study in 2014 and after the three-year follow-up in 2017/18 were analyzed. Results. Of 76 interviewed patients, 74 (97.4%) answered the questionnaire and were included in the study in 2014. After three years, 39.2% (29/74) answered the questionnaire again and in 59.8% (45/74) cannot apply MLHFQ a second time (deaths: 11; loss of follow-up at the service: 21; not found: 13). The mean score reached by the MLHFQ was 40.3 ± 21 points after inclusion and 31.6 ± 23 points after three years of follow-up at the service (p=0.001). Conclusion. We observed low QoL in the patients with HF included on this study, providing improvement of QoL after three years of follow-up at the specialized service. The HF clinics may significantly increase the QoL of HF patients, providing potential prognostic benefit.

Introducción. La insuficiencia cardíaca (IC) tiene una alta morbilidad y mortalidad, además de tener un gran impacto en la calidad de vida (CV). El cuestionario Minnesota Living with Heart Failure Questionnaire (MLHFQ) es un score de puntos que evalúa la CV de los pacientes con este síndrome, en la que una puntuación más alta refleja una menor CV. Objetivo. Evaluar la CV de pacientes con IC tras tres años de seguimiento en un servicio ambulatorio especializado de un hospital universitario. Métodos. Estudio unicéntrico, descriptivo y prospectivo en el que se aplicó el MLHFQ, de forma voluntaria y confidencial, a pacientes con IC con fracción de eyección reducida seguidos de forma ambulatoria en la clínica de IC. Los resultados del MLHFQ de los pacientes se analizaron comparando el tiempo de inclusión en el estudio, en 2014, y después de los tres años de seguimiento, en 2017/18. Resultados. De los 76 pacientes entrevistados inicialmente, 74 (97,4%) respondieron el cuestionario y fueron incluidos en el estudio en 2014. Después de un seguimiento de tres años, el 39,2% (29/74) de los pacientes respondieron el cuestionario nuevamente y en el 59,8% (45/74) no se pudo aplicar el MLHFQ por segunda vez (muertes: 11; pérdida de seguimiento en el servicio: 21; no localizado: 13). La puntuación media obtenida por el MLHFQ fue de 40,3 ± 21 puntos en el momento de la inclusión y de 31,6 ± 23 puntos tras tres años de seguimiento en el servicio (p=0,001). Conclusión. Se observó baja CV en los pacientes con IC incluidos en el estudio, con mejoría significativa a los tres años de seguimiento en el servicio especializado. Las clínicas de IC pueden aumentar significativamente la CV de los pacientes con IC, proporcionando un beneficio pronóstico potencial.

Clinicopathological study of cystic and atypical uterine leiomyoma: a rare entity / Estudo clinicopatológico de leiomioma uterino atípico e cístico: uma entidade rara

ABSTRACT A 43-years-old Brazilian woman, Caucasian, premenopausal, was attended with a history of lower abdominal pain, distension, and bleeding. Pelvic and transvaginal ultrasound revealed an enlarged uterus with a large, well-defined, uniformly hyperechoic lesion. The patient underwent total hysterectomy and the specimen was sent for anatomopathological evaluation. The histopathological analyses revealed a leiomyoma with extensive cystic degeneration and atypical characteristics, the immunohistochemical study confirmed the benignity of the case. The finding of atypical leiomyoma with cystic degeneration is rare and should be carefully evaluated to exclude malignant diseases.

RESUMEN Mujer brasileña de 43 años, caucásica, premenopáusica, fue atendida con antecedentes de dolor abdominal bajo, distensión y menorragias. La ecografía pélvica y transvaginal reveló un útero agrandado con una lesión grande, bien definida y uniformemente hiperecoica. La paciente fue sometida a histerectomía total y la pieza fue enviada para evaluación anatomo-patológica. Los análisis histopatológicos revelaron un leiomioma con degeneración quística extensa de características atípicas y la inmunohistoquímica confirmó la benignidad del caso. El hallazgo de un leiomioma atípico con degeneración quística es raro y debe evaluarse cuidadosamente para descartar enfermedades malignas.

RESUMO Mulher brasileira, 43 anos de idade, caucasiana, na pré-menopausa, foi atendida devido a história de dor em abdômen inferior, distensão e sangramento. A ultrassonografia pélvica e transvaginal revelou útero aumentado com grande lesão hiperecoica, bem definida e uniforme. A paciente foi submetida à histerectomia total, e a amostra foi enviada para avaliação anatomopatológica. A análise histopatológica revelou quadro de leiomioma com degeneração cística extensa e características atípicas; o estudo imuno-histoquímico confirmou a benignidade do caso. O achado de leiomioma atípico com degeneração cística é raro e deve ser cuidadosamente avaliado para excluir doenças malignas.

Oral hairy polyp in a teenager: case report and literature review / Pólipo piloso oral em um adolescente: relato de caso e revisão de literatura

ABSTRACT Objective: To report an unusual case of oral hairy polyp (HP) and review the literature, providing epidemiological, clinical and histopathological information on this disease. Case description: A 12-year-old male patient was referred to a Stomatology department with a nodule in the posterior midline of the tongue. The patient did not know exactly when it arose or whether it had grown since then. Clinical exam revealed a bulky and mobile pedunculated mass lesion on the dorsum of the tongue, with a diameter of approximately 1 cm. The patient's mother reported no previous health problem. An excisional biopsy was performed, the surgical specimen was sent for anatomopathological analysis, and the findings were compatible with the diagnosis of HP. Comments: Hairy polyp is a rare lesion, especially in the oral region. The literature search revealed only 10 case reports of oral HP published between January 1999 and January 2019, and they revealed a predominance of the disease in female newborns. Two uncommon facts were presented in this case: the patient was male and diagnosis was made at 12 years old.

RESUMO Objetivo: Relatar um caso incomum de pólipo piloso (PP) oral e revisar a literatura para trazer informações epidemiológicas, clínicas e histopatológicas acerca da doença. Descrição do caso: Paciente do sexo masculino, 12 anos de idade, encaminhado ao Departamento de Estomatologia com nódulo na região posterior de linha média da língua. O paciente não soube relatar quando surgiu a lesão e se ela havia crescido desde então. O exame clínico revelou massa pedunculada, volumosa e móvel no dorso da língua, medindo aproximadamente 1,0 cm de diâmetro. A mãe do paciente relatou que ele nunca havia tido nenhum problema de saúde anterior. Foi realizada biópsia excisional e o material foi enviado para análise anatomopatológica, sendo os achados compatíveis com o diagnóstico de PP. Comentários: O pólipo piloso é uma lesão rara, especialmente na região oral. A pesquisa bibliográfica revelou apenas dez relatos de casos de PP oral, publicados entre janeiro de 1999 e janeiro de 2019, sendo observada predominância da doença em recém-nascidos do sexo feminino. Dois fatos incomuns ocorreram neste caso: tratava-se de um paciente do sexo masculino e o diagnóstico se deu aos 12 anos de idade.

Analysis of Iron Metabolism in Chronic Chagasic Cardiomyopathy / Análise do Metabolismo do Ferro na Cardiomiopatia Chagásica Crônica

Abstract Changes in iron metabolism in heart failure (HF) have been described as an important prognostic marker. To check if the markers of iron kinetics are related to the morbidity and etiology of chagasic cardiomyopathy. Patients with Chronic Chagasic Cardiomyopathy (CCC, n = 40), with indeterminate form (IND, n = 40), besides non-chagasic cardiomyopathy (NCh, n = 40). The mean age was 50.98 ± 5.88 in CCC, 50% were male, 49.68 ± 5.28 in IND, 52.2% were male, and 49.20 ± 10.09 in NCh, 12.5% were male. Lower levels of iron (FeSe) were observed in the CCC groups (93.15 ± 36.53), when compared to IND (125.30 ± 22.79) and NCh (114.77 ± 18.90) (p = 0.0004), lower IST transferrin saturation index in CCC (29.48 ± 6.59), when compared to IND (30.95 ± 7.06) and in the NCh group (39.70 ± 7.54) p = 0.0001), total binding capacity of the lower CTLF iron in the CCC group (297.30 ± 36.46), when compared to the IND group (196.52 ± 56.95) and the NCh group (275.18 ± 33, 48) (p = 0.0001), lower ferritin in the CCC group (134.55, 1.56-42.36), when compared to the IND group (156,25, 1,72-42,20) and the NCh group (112.95, 2.88-42.66) (p = 0.0004). It was also observed that FeSe (95% CI 1.00-1.04, p = 0.0014), IST (95% CI 1.02-1.22) (p = 0.0012) and gender (95% CI 1.07-14.43 p = 0.0038) were independently associated with the degree of ventricular dysfunction in chagasic cardiomyopathy. CCC patients showed greater change in iron metabolism regarding the indeterminate form and other forms of cariomyopathies.

Resumo A alteração do metabolismo do ferro na insuficiência cardíaca (IC) tem sido descrita como um importante marcador prognóstico. Verificar se os marcadores da cinética do ferro guardam relação com a morbidade e a etiologia da cardiomiopatia chagásica. Pacientes com cardiomiopatia chagásica crônica (CCC, n = 40), com a forma indeterminada (IND, n = 40), além de cardiomiopatia não chagásica (NCh, n = 40). A idade média foi de 50,98 ± 5,88 no CCC, 50% eram do sexo masculino, 49,68 ± 5,28 no IND, 52,2% eram do sexo masculino e 49,20 ±10,09 no NCh, 12,5% eram do sexo masculino. Observaram-se níveis de ferro (FeSe) menores no grupos CCC (93,15 ± 36,53), quando comparados ao IND (125,30 ± 22,79) e NCh (114,77 ± 18,90) (p = 0,0004), índice de saturação de transferrina (IST) menor no CCC (29,48 ± 6,59), quando comparado ao IND (30,95 ± 7,06) e no grupo NCh (39,70 ± 7,54) (p= 0,0001), capacidade total de ligação do ferro CTLF menor no grupo CCC (297,30 ± 36,46), quando comparado ao grupo IND (196,52 ± 56,95) e ao grupo NCh (275,18 ± 33,48) (p = 0,0001), ferritina menor no grupo CCC (134,55, 1,56-42,36), quando comparada ao grupo IND (156,25, 1,72 - 42,20) e ao grupo NCh (112,95, 2,88-42,66) (p = 0.0004). Verificou-se também que o FeSe (IC% 95% 1,00-1,04; p = 0,0014), o IST (IC 95% 1,02-1,22) (p = 0,0012) e o sexo (IC 95% 1,07-14,43 p = 0,0038) associaram-se independentemente ao grau de disfunção ventricular na cardiomiopatia chagásica. Os pacientes com CCC demonstraram maior alteração no metabolismo do ferro em relação a forma indeterminada e outras formas de miocardiopatias.

Sexual determination and differentiation during embryonic and fetal development of New Zealand rabbit females / Determinación y diferenciación sexual durante el desarrollo embrionario y fetal de conejos hembras de Nueva Zelanda

The aim of this study was to know the embryonic and fetal development of the female rabbit genital system (Oryctolagus cuniculus), describing its main phases and the moment of sexual differentiation. Eleven pregnant New Zealand female rabbits were used in different gestational phases. The day of coitus was determined as day 0. For each stage a minimum of two animals was considered. The samples were obtained every two days from the ninth day post-coitus (dpc) until the 28th dpc. The gestational period was divided in two: animals with undifferentiated sex (group 1) and animals with differentiated sex (group 2). The ages of embryos and fetuses were estimated through the crown-rump method. Subsequently, embryos and fetuses were dissected, fixed and processed to be embedded in paraffin (Histosec). The histological analysis was performed on sections stained with hematoxylin and eosin. Immunohistochemical analysis to determine sexual differentiation was performed on samples from the 16th, 18th and 28th dpc. Desert Hedgehog (Dhh) and Indian Hedgehog (Ihh) primary antibodies, respectively, were used to identify cells of the male and female germinal epithelium. The immunohistochemical results showed that at the 16th dpc, female sexual differentiation was evident, since positive expression of the Ihh protein was observed. Sexual differentiation was obtained through histological analysis on the 18th dpc and through anatomical observation of the external genitalia on the 24th dpc. Knowing the characteristics of the embryonic and fetal development of the female rabbit genital system as well as the moment of sexual differentiation make it possible to establish bases for future research that address the physiology and pathology of these organs. Thus, any alteration in the chain of events of sexual determination and differentiation must search for an explanation from the knowledge of the possible normal mechanisms affected.

El objetivo de esta investigación fue conocer el desarrollo embrionario y fetal del sistema genital femenino de conejo (Oryctolagus cuniculus), describiendo sus principales fases y el momento de la diferenciación sexual. Se utilizaron 11 conejos hembras gestantes neozelandesas, en diferentes fases gestacionales. El día del coito se determinó como día 0. Para cada etapa fue considerado un mínimos de dos animales. Las muestras fueron obtenidas cada dos días, a partir del noveno día post-coito (dpc) hasta el 28 dpc. El periodo gestacional fue dividido en dos: animales con sexo indiferenciado (grupo 1) y, animales con sexo diferenciado (grupo 2). Las edades de los embriones y los fetos fueron estimadas a través del método de crown-rump. Posteriormente, embriones y fetos fueron disecados, fijados y procesados para su inclusión en parafina (Histosec). El análisis histológico se realizó en secciones teñidas con Hematoxilina y Eosina. El análisis inmunohistoquímico para determinar la diferenciación sexual fue realizado en muestras de 16, 18 y 28 dpc. Para identificar células del epitelio germinativo masculino y feminino se utilizaron los anticuerpos primarios Desert Hedgehog (Dhh) e Indian Hedgehog (Ihh), respectivamente. Los resultados inmunohistoquímicos mostraron que a los 16 dpc se evidenció diferenciación sexual femenina, ya que se observó expresión positiva de la proteína Ihh. La diferenciación sexual, a través del análisis histológico fue obtenida a los 18 dpc y a través de la observación anatómica de los genitales externos a los 24 dpc. Conocer las características del desarrollo embrionario y fetal del sistema genital femenino de conejo, así como, el momento de la diferenciación sexual, permiten sentar bases para futuras investigaciones que aborden la fisiología y patología de estos órganos. Así, cualquier alteración en la cadena de eventos de la determinación y diferenciación sexual deberá buscar una explicación a partir del conocimiento de los posibles mecanismos normales afectados.

Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica / Clinical applications of pharmacogenomics

Pharmacogenomics is an emergent field aimed at tailoring pharmacological therapy. Genetic polymorphisms can modify the expression and function of enzymes and proteins involved in drug metabolism, affecting absorption, distribution, biotransformation and excretion as well as the drug-target interaction. Therefore, the presence of allelic variants will classify people as poor, extensive or rapid/ultra rapid metabolizers, modifying drug efficacy and safety. In this work, the state of art in relation to this discipline is presented and the genetic variants of enzymes that are involved in drug pharmacokinetics or pharmacodynamics are described. The effects of these variants on the therapeutic response to drugs used in our country are also discussed.