Genetic ancestry and radical prostatectomy findings in Hispanic/Latino patients.

Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics. Results: No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03). Conclusion: Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.

Determination of ERG(+), EZH2, NKX3.1, and SPINK-1 subtypes to evaluate their association with clonal origin and disease progression in multifocal prostate cancer.

BACKGROUND: The prognostic relevance of prostate cancer (PCa) molecular subtypes remains controversial, given the presence of multiple foci with the possibility of different subtypes in the same patient. AIM: To determine the clonal origin of heterogeneity in PCa and its association with disease progression, SPOP, ERG(+), EZH2, NKX3.1, and SPINK-1 subtypes were analyzed. METHODS: A total of 103 samples from 20 PCa patients were analyzed; foci of adjacent non-tumor prostate tissue, HGPIN, GL3, GL4, GL5, and LN were examined to determine the presence of the TMPRSS2-ERG fusion and ERG, EZH2, NKX3.1, and SPINK-1 expression levels, using RT-PCR. Mutations in exons 6 and 7 of the SPOP gene were determined by sequencing. The presence of subtypes and molecular patterns were identified by combining all subtypes analyzed. To establish the clonal origin of multifocal PCa, molecular concordance between different foci of the same patient was determined. Association of these subtypes with histopathological groups and time to biochemical recurrence (BCR) was assessed. RESULTS: No mutation was found in SPOP in any sample. The ERG(+) subtype was the most frequent. The molecular pattern containing all four PCa subtypes was only detected in 3 samples (4%), all LN, but it was the most frequent (40%) in patients. Molecular discordance was the predominant status (55%) when all analyzed molecular characteristics were considered. It was possible to find all subtypes, starting as a preneoplastic lesion, and all but one LN molecular subtype were ERG(+) and NKX3.1 subtypes. Only the expression of the NKX3.1 gene was significantly different among the histopathological groups. No association was found between BCR time in patients and molecular subtypes or molecular concordance or between clinicopathological characteristics and molecular subtypes of ERG, EZH2, and SPINK-1. CONCLUSION: The predominance of molecular discordance in prostatic foci per patient, which reflects the multifocal origin of PCa foci, highlights the importance of analyzing multiple samples to establish the prognostic and therapeutic relevance of molecular subtypes in a patient. All the subtypes analyzed here are of early onset, starting from preneoplastic lesions. NKX3.1 gene expression is the only molecular characteristic that shows a progression pattern by sample.

Metabolic pathways enriched according to ERG status are associated with biochemical recurrence in Hispanic/Latino patients with prostate cancer.

BACKGROUND: The role of ERG-status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG-status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients. METHODS: RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA-sequencing. ERGhigh /ERGlow tumor groups were determined based on the 1.5-fold change median expression in non-tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change >2 were identified between ERGhigh and ERGlow tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed to evaluate biochemical recurrence (BCR)-free survival. RESULTS: The identification of 150 DEGs between ERGhigh and ERGlow tumors revealed clustering of most of the non-BCR cases (60%) into de ERGhigh group and most of the BCR cases (60.8%) in ERGlow group. Kaplan-Meier survival curves showed a worst BCR-free survival for ERGlow patients, and a significant reduced risk of BCR was observed for ERGhigh cases (OR = 0.29 (95%CI, 0.10-0.8)). Enrichment pathway analysis identified metabolic-related pathways, such as the renin-angiotensin system and angiotensin maturation system, the linoleic acid metabolism, and polyamines metabolism in these ERG groups. CONCLUSIONS: ERGlow tumor cases were associated with poor BCR-free survival in our Hispanic/Latino patients, with metabolism-related pathways altered in the BCR progression. IMPACT: Our findings suggest the need to dissect the role of diet, metabolism, and lifestyle as risk factors for more aggressive PCa subtypes.

La importancia de la determinación del HER2 en el cáncer gástrico avanzado: a propósito de un caso clínico / Importance of HER2 status determination in advanced gastric cancer: A case study

Resumen El cáncer gástrico avanzado es una entidad que incluye dos situaciones clínicas distintas: el cáncer gástrico localmente avanzado no resecable y la enfermedad metastásica, cuyo tratamiento estándar es la quimioterapia. La sobreexpresión del receptor 2 del factor de crecimiento epidérmico humano (HER2) se puede presentar en esta enfermedad de un 9 % a un 38 % y ha sido el primer biomarcador predictivo utilizado para el tratamiento dirigido con trastuzumab en pacientes con tumores gástricos y de la región gastroesofágica avanzados. Se presenta en este artículo el caso de un paciente con cáncer gástrico avanzado con HER2 positivo manejado con quimioterapia convencional más trastuzumab como terapia blanco con adecuada respuesta clínica.

Abstract Advanced gastric cancer (AGC) is an entity that encompasses two distinct clinical situations: locally advanced unresectable gastric cancer and metastatic disease, with chemotherapy as the standard treatment. HER2 overexpression can occur in 9% to 38% of the cases with this disease and has been the first predictive biomarker used for trastuzumab-targeted therapy in patients with advanced gastric and gastroesophageal tumors. This article presents a patient with AGC and positive HER2 treated with conventional chemotherapy plus trastuzumab as targeted therapy with adequate clinical response.

Decoding the heterogeneous landscape in the development prostate cancer.

Prostate cancer (PCa) is characterized as being histologically and molecularly heterogeneous; however, this is not only incorrect among individuals, but also at the multiple foci level, which originates in the prostate gland itself. The reasons for such heterogeneity have not been fully elucidated; however, understanding these may be crucial in determining the course of the disease. PCa is characterized by a complex network of chromosomal rearrangements, which simultaneously deregulate multiple genes; this could explain the appearance of exclusive events associated with molecular subtypes, which have been extensively investigated to establish clinical management and the development of therapies targeted to this type of cancer. From a clinical aspect, the prognosis of the patient has focused on the characteristics of the index lesion (the largest focus in PCa); however, a significant percentage of patients (11%) also exhibit an aggressive secondary foci, which may determine the prognosis of the disease, and could be the determining factor of why, in different studies, the classification of the subtypes does not have an association with prognosis. Due to the aforementioned reasons, the analysis of molecular subtypes in several foci, from the same individual could assist in determining the association between clinical evolution and management of patients with PCa. Castration-resistant PCa (CRPC) has the worst prognosis and develops following androgen ablation therapy. Currently, there are two models to explain the development of CRPC: i) The selection model and ii) the adaptation model; both of which, have been found to include alterations described in the molecular subtypes, such as Enhancer of zeste 2 polycomb repressive complex 2 subunit overexpression, isocitrate dehydrogenase (NAPD+)1 and forkhead box A1 mutations, suggesting that the presence of specific molecular alterations could predict the development of CRPC. This type of analysis could lead to a biological understanding of PCa, to develop personalized medicine strategies, which could improve the response to treatment thus, avoiding the development of resistance. Therefore, the present review discusses the primary molecular factors, to which variable heterogeneity in PCa progress has been attributed.

Biomarcadores de pronóstico en pacientes con cáncer de próstata localizado / Prognostic biomarkers in patients with localised prostate cancer

Resumen El tratamiento para cáncer de próstata localizado (prostatectomía radical o radioterapia) ofrece unas altas tasas de curación; sin embargo, del 20 al 30% de los casos desarrollan recurrencia bioquímica. Actualmente, existen factores clínicos y patológicos que ayudan a predecir recurrencia; no obstante tanto el carácter heterogéneo de estos tumores, las diferencias en los tiempos de progresión de cáncer localizado a metastásico como la resistencia al tratamiento han dado lugar a imprecisiones en la predicción del pronóstico y a tratamientos insuficientes o excesivos. Debido a esto se han estudiado biomarcadores con el fin de estratificar más acertadamente el riesgo y mejorar las decisiones de tratamiento de una manera adecuada y oportuna. Este manuscrito presenta una revisión de marcadores moleculares de pronóstico que se han propuesto en los pacientes con cáncer de próstata localizado, lo que podría permitir establecer con mayor precisión el riesgo de recurrencia de la enfermedad.

Abstract Treatment for localised prostate cancer (radical prostatectomy or radiotherapy), offers high cure rates; nevertheless, 20% to 30% of the cases develop biochemical recurrence. There are clinical and pathological features that are currently being used to predict recurrence of the disease. However, tumour heterogeneity in prostate cancer, along with differences in time of progression to metastasis and treatment resistance, have led to inaccuracies in predicting the risk of biochemical relapse, and therefore, misleading in treatment decisions. Because of this, many genetic markers have been studied in order to refine risk stratification and improve treatment decisions in a suitable and opportune manner. This paper presents a review of molecular prognostic markers that have been proposed in patients with localised prostate cancer, which potentially could allow establishing the risk of recurrence of the disease more accurately.

Tres cánceres primarios simultáneos: reporte de caso y revisión de la literatura / Three simultaneous primary cancers: Case report and literature review

Resumen La presencia de un segundo o tercer cáncer primario después del diagnóstico inicial de malignidad es un evento cada vez más frecuente asociado con la mejor sobrevida y seguimiento de pacientes con cáncer a nivel mundial. Sin embargo, la presencia de tres neoplasias primarias simultáneas sigue siendo un evento singular. Presentamos el caso de una mujer de 76 años con tumor neuroendocrino del intestino delgado, adenocarcinoma de colon sigmoide y adenocarcinoma mucinoso de ovario de manera simultánea, manejada quirúrgicamente. Reali zamos una revisión de la literatura.

Abstract The presence of a second or third primary cancer after the initial diagnosis of malig nancy is an increasingly frequent event associated with the improved survival and monitoring of cancer patients worldwide. However, the presence of three simultaneous primary neoplasms remains a singular event. The case is presented of a 76-year-old woman with a neuroendo crine tumour of the small intestine, sigmoid colon adenocarcinoma, and a mucinous ovarian adenocarcinoma, simultaneously surgically managed. A literature review on the topic was also conducted.

Tumores estromales gastrointestinales (GIST) en el Instituto Nacional de Cancerología, Bogota D.C., Colombia 2000-2008 / Gastrointestinal stromal tumors (GIST) at the National Cancer Institute, Bogota D.C., Colombia 2000-2008

Objetivo: Describir las características demográficas, clínicas y patológicas, así como el diagnóstico, el tratamiento y el seguimiento de los pacientes con tumores estromales gastrointestinales (GIST) del Instituto Nacional de Cancerología (INC) durante el periodo comprendido entre 2000 y 2008. Métodos: Estudio retrospectivo, de 39 pacientes con diagnóstico de GIST, donde se analizan las características clínicas los diagnósticos patológico y de inmunohistoquímica, al igual que los factores pronósticos, como tamaño, conteo mitótico y localización. Se revisa los manejos quirúrgico y médico, el seguimiento y la recurrencia, de acuerdo con la localización de las lesiones. Resultados: Se incluyó a 39 pacientes, con edad promedio de 53 años. La localización más habitual fue el estómago, con 16 casos, seguida del intestino delgado, con 9. De los pacientes, 24 presentaban lesiones mayores a 10 cm y, 19 con lesiones que microscópicamente mostraban menos de 5 mitosis x50 campos. Excepto una, todas las lesiones fueron positivas para CD117. El síntoma más habitual fue el dolor abdominal. De los 39 pacientes, 7 tenían metástasis al momento del diagnóstico. Al 43,7% de los pacientes se les tomó biopsia preoperatoria, y 38 pacientes fueron llevados a cirugía; 8 de ellos, por obstrucción intestinal con localización en el intestino delgado. El tiempo de seguimiento osciló entre 2 y 72 meses. Se presentaron 16 recaídas, con una tasa de 1,26 x 100 pacientes. La supervivencia media fue de 48,53 meses. Conclusiones: Los GIST son un grupo de tumores de mayor diagnóstico cada día, debido a la sospecha clínica y al diagnóstico por inmunohistoquímica. El manejo es, primordialmente, quirúrgico, pero en la actualidad la adyuvancia y la neoadyuvancia con ITK son parte del manejo de esta patología.

Objective: To describe the demographic, clinical and pathological characteristics, as well as diagnosis, treatment and follow up in patients with gastrointestinal stromal tumors (GIST) at the National Cancer Institute (NCI) between 2000 and 2008. Methods: A retrospective study was carried out on 39 patients diagnosed with GIST in which the diagnostic pathology and immunohistochemical clinical characteristics were analyzed, as were prognostic factors such as size, mitotic count and localization. Surgical and medical procedures along with follow up and recurrence were reviewed in relation to lesion localization. Results: The study included 39 patients with an average age of 53 years. Most common localization was the stomach (16 cases), followed by the small intestine (9 cases). Out of total number of patients, 24 had lesions greater than 10 cm. and 19 had lesions less than 5 mitosis x 50 fields. All but one lesion tested CD117 positive. Abdominal pain was the most common symptom. Of the 39 patients, 7 had metastasis at time of diagnosis. Preoperative biopsy was taken on 43.7% of patients, and 38 patients underwent surgery; 8 of whom for intestinal obstruction in the small intestine. Follow up ranged from 2 to 72 months. Relapse occurred in 16 cases, for a rate of 1.26 per 100 patients. Median survival rate was 48.53 months. Conclusions: GISTs make up a group of tumors with ever increasing diagnosis due to clinical suspicion and immunohistochemical diagnosis. Treatment is primarily surgical, but adjuvant and neo-adjuvant ITK treatment are currently used to treat this pathology.