ZEB1 hypermethylation is associated with better prognosis in patients with colon cancer.

BACKGROUND: Colon cancer (CC) is a heterogeneous disease that is categorized into four Consensus Molecular Subtypes (CMS) according to gene expression. Patients with loco-regional CC (stages II/III) lack prognostic factors, making it essential to analyze new molecular markers that can delineate more aggressive tumors. Aberrant methylation of genes that are essential in crucial mechanisms such as epithelial mesenchymal transition (EMT) contributes to tumor progression in CC. We evaluate the presence of hyper- and hypomethylation in subrogate IHC markers used for CMS classification (CDX2, FRMD6, HTR2B, ZEB1) of 144 stage II/III patients and CC cell lines by pyrosequencing. ZEB1 expression was also studied in control and shRNA-silenced CC cell lines and in paired normal tissue/tumors by quantitative PCR. The pattern of ZEB1 staining was also analyzed in methylated/unmethylated tumors by immunohistochemistry. RESULTS: We describe for the first time the hypermethylation of ZEB1 gene and the hypomethylation of the FRMD6 gene in 32.6% and 50.9% of tumors, respectively. Additionally, we confirm the ZEB1 re-expression by epigenetic drugs in methylated cell lines. ZEB1 hypermethylation was more frequent in CMS1 patients and, more importantly, was a good prognostic factor related to disease-free survival (p = 0.015) and overall survival (p = 0.006) in our patient series, independently of other significant clinical parameters such as patient age, stage, lymph node involvement, and blood vessel and perineural invasion. CONCLUSIONS: Aberrant methylation is present in the subrogate genes used for CMS classification. Our results are the first evidence that ZEB1 is hypermethylated in CC and that this alteration is an independent factor of good prognosis.

[Intraepidermal Merkel cell carcinoma with INSM1 expression. A case report]. / Carcinoma de Merkel intraepidérmico. Presentación de un caso con expresión de INSM1.

We report the case of a 90-year-old male who presented with an erythematous desquamative plaque on his left cheek. Histopathology demonstrated an epidermal lesion with multifocal epithelial growth. The cells were small, with scant cytoplasm and hyperchromatic nuclei with molding and a high mitotic and apopototic rate. Immunohistochemistry showed positivity for CK20, CK7, synaptophysin and INMS1. These findings are consistent with a Merkel cell carcinoma in situ. This tumor corresponds to a primary neuroendocrine neoplasm of the skin, which usually affects elderly people with sun-exposed skin. Usually, it presents as a dermal tumor but intraepidermal involvement alone is extremely rare. In this scenario, a broad differential diagnosis should be considered, excluding all neoplasms that may present intraepidermal forms. The evolution of this entity is unknown.

Carcinoma adenoide quístico de mama, 22 años de experiencia / Adenoid cystic carcinoma of the breast, 22 years of experience

INTRODUCCIÓN: El carcinoma adenoide quístico (CAQ) es una neoplasia infrecuente en la mama (menos del 0,1%). Típicamente es triple negativo con un pronóstico favorable. Su baja frecuencia y su curso indolente provocan dificultades en el convenio de la evaluación y el consenso terapéutico, así como en el uso de la técnica del ganglio centinela en estos carcinomas. OBJETIVO: Aportar una serie nueva de casos procedentes del Complejo Hospitalario de Navarra, mediante la revisión retrospectiva en un periodo de 22 años. MATERIAL Y MÉTODOS: Se revisan todos los casos de CAQ mamario diagnosticados entre 1998 y 2020. Analizamos los datos clínicos y anatomopatológicos y los comparamos con la literatura. RESULTADOS: Identificamos 12 CAQ, de un total de 18.241 pacientes con diagnóstico de carcinoma de mama, con un tamaño tumoral medio de 23,8mm y una edad media de 63,5 años. Todos ellos se encontraban en un estadio I-II al diagnóstico. Un caso presentó una micrometástasis ganglionar. Un caso presentó recidiva local y un caso presentó metástasis a distancia a los 5 meses del diagnóstico (93,5 meses de seguimiento medio). Según el grado histológico de Nottingham, 8 casos tuvieron un grado 1, 2 casos un grado 2 y 2 pacientes un grado 3. Según la clasificación de Ro et al., 3 casos fueron grado 1, 4 casos grado 2 y 5 casos grado 3. Un caso fue RE positivo (10%). Ningún caso presentó positividad para BRAF V600E con inmunohistoquímica. CONCLUSIÓN: El manejo y pronóstico del CAQ mamario, dentro de la benignidad, sigue siendo incierto, siendo necesarios más datos para comprender la evolución clínica y realizar un adecuado manejo terapéutico

INTRODUCTION: Adenoid cystic carcinoma (ACC) is an uncommon neoplasm in the breast (less than 0.1%). ACC is typically triple negative with a favourable prognosis. Its low frequency and indolent course cause difficulties in the agreement of the evaluation and therapeutic consensus, as well as the use of the sentinel node excision in these carcinomas. OBJECTIVE: Our goal is to provide a new series of cases from the Complejo Hospitalario de Navarra, through retrospective review over a period of 22 years. MATERIAL AND METHODS: Every case of breast ACC diagnosed between 1998-2020 is reviewed. We analyze the clinical and pathological characteristics, and compare them with the literature. RESULTS: We identified twelve cases of ACC, from a total of 18,241 patients diagnosed with breast carcinoma, with an average tumor size of 23.8mm and mean of 63.5 years. All of them were in a stage I-II at diagnosis. One case presented a lymph node micrometastases. One of them presented local recurrences and one case presented metastases 5 months after diagnosis (93.5 months of mean follow-up). According to Nottingham Histological Score, eight cases had a grade 1, two grade 2 and two grade 3. According to the classification of Ro et al., three were grade 1, four grade 2 and five grade 3. One case was ER positive (10%). No case presents positivity for BRAF-V600E in immunohistochemistry. CONCLUSION: The management and prognosis ACC of breast, within benignity, remains uncertain, with more studies being needed to understand the clinical evolution and perform adequate therapeutic management

[Adenoid cystic carcinoma of the breast, 22 years of experience]. / Carcinoma adenoide quístico de mama, 22 años de experiencia.

INTRODUCTION: Adenoid cystic carcinoma (ACC) is an uncommon neoplasm in the breast (less than 0.1%). ACC is typically triple negative with a favourable prognosis. Its low frequency and indolent course cause difficulties in the agreement of the evaluation and therapeutic consensus, as well as the use of the sentinel node excision in these carcinomas. OBJECTIVE: Our goal is to provide a new series of cases from the Complejo Hospitalario de Navarra, through retrospective review over a period of 22 years. MATERIAL AND METHODS: Every case of breast ACC diagnosed between 1998-2020 is reviewed. We analyze the clinical and pathological characteristics, and compare them with the literature. RESULTS: We identified twelve cases of ACC, from a total of 18,241 patients diagnosed with breast carcinoma, with an average tumor size of 23.8mm and mean of 63.5 years. All of them were in a stage I-II at diagnosis. One case presented a lymph node micrometastases. One of them presented local recurrences and one case presented metastases 5 months after diagnosis (93.5 months of mean follow-up). According to Nottingham Histological Score, eight cases had a grade 1, two grade 2 and two grade 3. According to the classification of Ro et al., three were grade 1, four grade 2 and five grade 3. One case was ER positive (10%). No case presents positivity for BRAF-V600E in immunohistochemistry. CONCLUSION: The management and prognosis ACC of breast, within benignity, remains uncertain, with more studies being needed to understand the clinical evolution and perform adequate therapeutic management.