Caracterización histológica del melanoma cutáneo en reportes de patología en la ciudad de Cali, 2016-2021 / Histological characterization of cutaneous melanoma in pathology reports in the city of Cali, 2016-2021

Introducción. El melanoma es la proliferación maligna de melanocitos asociado a un comportamiento agresivo. El objetivo de este estudio fue determinar las variables histológicas del melanoma cutáneo. Métodos. Estudio observacional retrospectivo, transversal descriptivo, realizado con reportes de patologías de pacientes con diagnóstico de melanoma cutáneo en un laboratorio de patología en Cali, Colombia, entre 2016-2021. Se incluyeron las variables edad, sexo, localización, subtipo, espesor de Breslow, ulceración, márgenes, mitosis, invasión linfovascular, neurotrofismo, regresión tumoral, nivel de Clark e infiltración tumoral por linfocitos. Resultados. Se obtuvieron 106 reportes y fueron excluidos 54 por duplicación. Se incluyeron 52 registros, la media de edad fue de 61 años, con una mayor frecuencia de mujeres (55,8 %). De los 33 casos donde se especificó el subtipo histológico, el más frecuente fue el de extensión superficial (66,6 %), seguido del acral lentiginoso (18,1 %) y nodular con (15,2 %). La localización más frecuente fue en extremidades (61,5 %). El espesor de Breslow más común fue IV (34,6 %) y el nivel de Clark más frecuente fue IV (34,6 %). La ulceración estuvo en el 40,4 %. El subtipo nodular fue el de presentación más agresiva, donde el 100 % presentaron espesor de Breslow IV. Conclusiones. El subtipo de melanoma más común en nuestra población fue el de extensión superficial; el segundo en frecuencia fue el subtipo acral lentiginoso, que se localizó siempre en extremidades. Más del 50 % de los melanomas tenían espesor de Breslow mayor o igual a III, lo que impacta en el pronóstico.

Background. Melanoma is the malignant proliferation of melanocytes associated with aggressive behavior. The objective of this study was to determine the histological variables of cutaneous melanoma. Methods. Observational, cross-sectional, descriptive, retrospective study carried out with reports of pathologies with a diagnosis of cutaneous melanoma in a pathology laboratory in Cali between 2016-2021. The variables were age, sex, location, subtype, Breslow thickness, ulceration, margins, mitosis, lymphovascular invasion, neurotropism, tumoral regression, Clark level and tumor infiltration by lymphocytes. Results. One hundred and six reports were obtained and 54 were excluded due to duplication. A descriptive analysis was made on the 52 records that were included, the mean age was 61 years, with a higher frequency in women with 55.8%. Of the 33 cases where the histological subtype was specified, the most frequent was superficial extension with 66.6%, followed by acral lentiginous with 18.1% and nodular with 15.2%. The most frequent location was in the extremities (61.5%); the most common Breslow was IV (34.6%), and the most frequent Clark was IV (34.6%). Ulceration was in 40.4%. The nodular subtype was the most aggressive presentation where 100% presented Breslow IV. Conclusions. The most common subtype of melanoma was that of superficial extension. In our population, the second most frequent was the acral lentiginous subtype, which was always located on the extremities. More than 50% of the melanomas had Breslow greater than or equal to III, which affects the prognosis.

Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia.

BACKGROUND: The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. METHODS: BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. RESULTS: The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. CONCLUSIONS: Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening.

Breast cancer in six families from Tolima and Huila: BRCA1 3450del4 mutation / [Cáncer de mama en seis familias del Tolima y el Huila: mutación BRCA1 3450del4].

Introduction: Breast cancer is a worldwide public health problem; between 5% and 10% of the cases present familial aggregation explained by genes of high risk such as BRCA1 and BRCA2. The founding origin of the deletion BRCA1 3450del4 in Colombia has been previously reported. Objective: To carry out in six families from Tolima and Huila departments a descriptive analysis of the presence of the BRCA1 3450del4 mutation associated with breast cancer and familial aggregation. Materials and methods: We conducted a descriptive and cross-sectional study of six index cases with breast cancer positive for BRCA1 3450del4 that fulfilled three of the criteria established by Jalkh, et al. The genealogical trees were made using the information of the interview data (GenoPro™, version 2016). The mutation was typified in healthy and affected relatives who agreed to participate. Results: Thirty of the 78 individuals selected by convenience in the six families presented the mutation BRCA1 3450del4 six of whom developed breast cancer, one, ovarian cancer, one ovarian and breast cancer, and one prostate cancer; 21 did not present any type of neoplasm at the time of the study. Of the 30 individuals carrying the pathogenic variant, six were men, 24 were women, and 13 of these were under 30. Conclusions: In this study of families with the deletion BRCA1 3450del4 in Tolima and Huila we confirmed its association with familial aggregation of breast cancer.

Introducción. El cáncer de mama es un problema mundial de salud pública; entre el 5 y el 10 % de los casos presentan agregación familiar, lo que se explicaría por la presencia de mutaciones en genes de alto riesgo como el BRCA1 y el BRCA2. El origen fundador de la deleción BRCA1 3450del4 en Colombia ya fue reportado. Objetivo. Hacer un análisis descriptivo de seis familias del del Tolima y del Huila con la deleción BRCA1 3450del4 de la asociación de la mutación germinal, con el cáncer de mama y la agregación familiar. Materiales y métodos. Se hizo un estudio descriptivo y transversal de seis casos índice con cáncer de mama positivos para BRCA1 3450del4, que cumplían tres de los criterios establecidos por Jalkh, et al. A partir de la información de las entrevistas, se realizaron los árboles genealógicos (GenoPro™, versión 2016). Se tipificó la mutación en familiares sanos y afectados que aceptaron participar. Resultados. De los 78 individuos seleccionados por conveniencia en las seis familias, 30 presentaron la mutación BRCA1 3450del4; de ellos, seis tenían cáncer de mama, uno, cáncer de ovario, uno, cáncer de mama y ovario, y otro, cáncer de próstata; 21 no presentaban neoplasias. De los 30 individuos portadores de la variante patogénica, seis eran hombres y 24 mujeres, 13 de ellas menores de 30 años. Conclusiones. En este estudio se confirmó la asociación de la deleción BRCA1 3450del4 con el cáncer de mama de agregación familiar.

Cáncer de mama en seis familias del Tolima y el Huila: mutación BRCA1 3450del4 / Breast cancer in six families from Tolima and Huila: BRCA1 3450del4 mutation

Introducción. El cáncer de mama es un problema mundial de salud pública; entre el 5 y el 10 % de los casos presentan agregación familiar, lo que se explicaría por la presencia de mutaciones en genes de alto riesgo como el BRCA1 y el BRCA2. El origen fundador de la deleción BRCA1 3450del4 en Colombia ya fue reportado. Objetivo. Hacer un análisis descriptivo de seis familias del del Tolima y del Huila con la deleción BRCA1 3450del4 de la asociación de la mutación germinal, con el cáncer de mama y la agregación familiar. Materiales y métodos. Se hizo un estudio descriptivo y transversal de seis casos índice con cáncer de mama positivos para BRCA1 3450del4, que cumplían tres de los criterios establecidos por Jalkh, et al. A partir de la información de las entrevistas, se realizaron los árboles genealógicos (GenoPro™, versión 2016). Se tipificó la mutación en familiares sanos y afectados que aceptaron participar. Resultados. De los 78 individuos seleccionados por conveniencia en las seis familias, 30 presentaron la mutación BRCA1 3450del4; de ellos, seis tenían cáncer de mama, uno, cáncer de ovario, uno, cáncer de mama y ovario, y otro, cáncer de próstata; 21 no presentaban neoplasias. De los 30 individuos portadores de la variante patogénica, seis eran hombres y 24 mujeres, 13 de ellas menores de 30 años. Conclusiones. En este estudio se confirmó la asociación de la deleción BRCA1 3450del4 con el cáncer de mama de agregación familiar.

Introduction: Breast cancer is a worldwide public health problem; between 5% and 10% of the cases present familial aggregation explained by genes of high risk such as BRCA1and BRCA2. The founding origin of the deletion BRCA1 3450del4 in Colombia has been previously reported. Objective: To carry out in six families from Tolima and Huila departments a descriptive analysis of the presence of the BRCA1 3450del4 mutation associated with breast cancer and familial aggregation. Materials and methods: We conducted a descriptive and cross-sectional study of six index cases with breast cancer positive for BRCA1 3450del4 that fulfilled three of the criteria established by Jalkh, et al. The genealogical trees were made using the information of the interview data (GenoPro™, version 2016). The mutation was typified in healthy and affected relatives who agreed to participate. Results: Thirty of the 78 individuals selected by convenience in the six families presented the mutation BRCA1 3450del4 six of whom developed breast cancer, one, ovarian cancer, one ovarian and breast cancer, and one prostate cancer; 21 did not present any type of neoplasm at the time of the study. Of the 30 individuals carrying the pathogenic variant, six were men, 24 were women, and 13 of these were under 30. Conclusions: In this study of families with the deletion BRCA1 3450del4 in Tolima and Huila we confirmed its association with familial aggregation of breast cancer.

BRAF and TERT mutations in papillary thyroid cancer patients of Latino ancestry.

Papillary thyroid cancer (PTC) is the second most commonly diagnosed malignancy in U.S. Latinas and in Colombian women. Studies in non-Latinos indicate that BRAF and TERT mutations are PTC prognostic markers. This study aimed to determine the prevalence and clinical associations of BRAF and TERT mutations in PTC Latino patients from Colombia. We analyzed mutations of BRAF (V600E) and TERT promoter (C228T, C250T) in tumor DNA from 141 patients (75 with classical variant PTC, CVPTC; 66 with follicular variant PTC, FVPTC) recruited through a multi-center study. Associations between mutations and clinical variables were evaluated with Fisher exact tests. Survival was evaluated with Kaplan-Meier plots. Double-mutant tumors (BRAF+/TERT+, n = 14 patients) were more common in CVPTC (P = 0.02). Relative to patients without mutations (n = 48), double mutations were more common in patients with large tumors (P = 0.03), lymph node metastasis (P = 0.01), extra-thyroid extension (P = 0.03), and advanced stage (P = 6.0 × 10-5). In older patients, TERT mutations were more frequent (mean age 51 years vs 45 years for wild type TERT, P = 0.04) and survival was lower (HR = 1.20; P = 0.017); however, given the small sample size, the decrease in survival was not statically significant between genotypes. Comparisons with published data in US whites revealed that Colombian patients had a higher prevalence of severe pathological features and of double-mutant tumors (10 vs 6%, P = 0.001). Mutations in both oncogenes show prognostic associations in Latinos from Colombia. Our study is important to advance Latino PTC precision medicine and replicates previous prognostic associations between BRAF and TERT in this population.

Clinical manifestations of colorectal cancer patients from a large multicenter study in Colombia.

Colorectal cancer (CRC) is a major public health problem, and its incidence is rising in developing countries. However, studies characterizing CRC clinicopathological features in cases from developing countries are still lacking. The goal of this study was to evaluate clinicopathological and demographic features in one of the largest CRC studies in Latin America.The study involved over 1525 CRC cases recruited in a multicenter study in Colombia between 2005 and 2014 as part of ongoing genetic and epidemiological studies. We gathered clinicopathological data such as age at diagnosis, sex, body mass index, tobacco and alcohol consumption, family history of cancer, and tumor features including location, histological type, and stage. Statistical analyses were performed to test the association between age of onset, sex, and clinical manifestations.The average age at CRC diagnosis was 57.4 years, with 26.5% of cases having early-onset CRC (diagnosed by age 50 years). Most cases were women (53.2%; P = 0.009), 49.2% were overweight or obese, 49.1% were regular alcohol drinkers, 52% were smokers/former smokers, and 12.2% reported relatives with cancer. Most tumors in the study were located in the rectum (42.7%), were adenocarcinomas (91.5%), and had advanced stage (T3-T4, 79.8%). Comparisons by sex found that male cases were more likely to be obese (36.5% vs 31.1%; P = 0.001), less likely to have a family history of cancer (9.7% vs 15.3%; P = 0.016), and more likely to have advanced-stage tumors (83.9% vs 76.1%; P = 0.036). Comparisons by age of onset found that early-onset cases were more likely to be women (59.3% vs 51.0%; P = 0.005) and report a family history of cancer (17.4% vs 10.2%; P = 0.001).To our knowledge, our study is the largest report of clinicopathological characterization of Hispanic CRC cases, and we suggest that further studies are needed to understand CRC etiology in diverse Hispanic populations.

Clinical features of Hispanic thyroid cancer cases and the role of known genetic variants on disease risk.

Thyroid cancer (TC) is the second most common cancer among Hispanic women. Recent genome-wide association (GWA) and candidate studies identified 6 single nucleotide polymorphisms (SNPs; rs966423, rs2439302, rs965513, rs6983267, rs944289, and rs116909374), associated with increased TC risk in Europeans but their effects on disease risk have not been comprehensively tested in Hispanics. In this study, we aimed to describe the main clinicopathological manifestations and to evaluate the effects of known SNPs on TC risk and on clinicopathological manifestations in a Hispanic population.We analyzed 281 nonmedullary TC cases and 1146 cancer-free controls recruited in a multicenter population-based study in Colombia. SNPs were genotyped by Kompetitive allele specific polymerase chain reaction (KASP) technique. Association between genetic variants and TC risk was assessed by computing odds ratios (OR) and confidence intervals (CIs).Consistent with published data in U.S. Hispanics, our cases had a high prevalence of large tumors (>2 cm, 43%) and a high female/male ratio (5:1). We detected significant associations between TC risk and rs965513A (OR = 1.41), rs944289T (OR = 1.26), rs116909374A (OR = 1.96), rs2439302G (OR = 1.19), and rs6983267G (OR = 1.18). Cases carried more risk alleles than controls (5.16 vs. 4.78, P = 4.8 × 10). Individuals with ≥6 risk alleles had >6-fold increased TC risk (OR = 6.33, P = 4.0 × 10) compared to individuals with ≤2 risk alleles. rs944289T and rs116909374A were strongly associated with follicular histology (ORs = 1.61 and 3.33, respectively); rs2439302G with large tumors (OR = 1.50); and rs965513A with regional disease (OR = 1.92).To our knowledge, this is the first study of known TC risk variants in South American Hispanics and suggests that they increase TC susceptibility in this population and can identify patients at higher risk of severe disease.

The HABP2 G534E polymorphism does not increase nonmedullary thyroid cancer risk in Hispanics.

Familial nonmedullary thyroid cancer (NMTC) has not been clearly linked to causal germline variants, despite the large role that genetic factors play in risk. Recently, HABP2 G534E (rs7080536A) has been implicated as a causal variant in NMTC. We have previously shown that the HABP2 G534E variant is not associated with TC risk in patients from the British Isles. Hispanics are the largest and the youngest minority in the United States and NMTC is now the second most common malignancy in women from this population. In order to determine if the HABP2 G534E variant played a role in NMTC risk among Hispanic populations, we analyzed 281 cases and 1105 population-matched controls from a multicenter study in Colombia, evaluating the association through logistic regression. We found that the HABP2 G534E variant was not significantly associated with NMTC risk (P=0.843) in this Hispanic group. We also stratified available clinical data by multiple available clinicopathological variables and further analyzed the effect of HABP2 on NMTC presentation. However, we failed to detect associations between HABP2 G534E and NMTC risk, regardless of disease presentation (P≥0.273 for all cases). Therefore, without any significant associations between the HABP2 G534E variant and NMTC risk, we conclude that the variant is not causal of NMTC in this Hispanic population.

Caracterización de los hallazgos histopatológicos de tumores colorrectales en pacientes del Tolima, Colombia / Characterization of histopathological findings from colorectal tumors from patients in Tolima

En Colombia, el cáncer colorectal es reconocido como un importante problema de salud pública, con una tendencia general al incremento en ambos géneros; se ubica entre los cinco primeros lugares en relación con la mortalidad. Teniendo en cuenta los diagnósticos histopatológicos reunidos entre enero de 2000 y diciembre de 2007, se realizó un análisis descriptivo retrospectivo en 191 pacientes tolimenses con tumores colorrectales tipo adenocarcinoma; estos fueron seleccionados en cinco centros de patología de la ciudad de Ibagué, mediante pruebas descriptivas básicas empleando el método porcentual. Los datos más sobresalientes corresponden a la edad al momento del diagnóstico (promedio mayor de 60 años), localización en el recto (34,6%) y en el colon izquierdo (28,3%) y aumento de los adenomas tubulovelloso y velloso.

In Colombia, colorectal cancer is recognized as a major public health problem. Its general tendency is occur more frequently among both genders. It now ranks among the top five in terms of mortality. Using histopathological diagnoses collected from pathology laboratories in Ibagué, Tolima between January 2000 and December 2007, we conducted a retrospective analysis of 191 patients who had colorectal adenocarcinoma. The most important findings are that the average age of diagnosis was over 60 years, most common tumor locations were in the rectum (34.6%) and in the left colon (283%), and the greatest numbers of tumors were tubulovillous adenoma, or villous adenoma. Most of cases were tubular.