ABSTRACT
The current standard of care for locally advanced rectal cancer (RC) is neoadjuvant radio-chemotherapy (NRC) with 5-fluorouracil (5Fu) as the main drug, followed by surgery and adjuvant chemotherapy. While a group of patients will achieve a pathological complete response, a significant percentage will not respond to the treatment. The Unfolding Protein Response (UPR) pathway is generally activated in tumors and results in resistance to radio-chemotherapy. We previously showed that RHBDD2 gene is overexpressed in the advanced stages of colorectal cancer (CRC) and that it could modulate the UPR pathway. Moreover, RHBDD2 expression is induced by 5Fu. In this study, we demonstrate that the overexpression of RHBDD2 in CACO2 cell line confers resistance to 5Fu, favors cell migration, adhesion and proliferation and has a profound impact on the expression of both, the UPR genes BiP, PERK and CHOP, and on the cell adhesion genes FAK and PXN. We also determined that RHBDD2 binds to BiP protein, the master UPR regulator. Finally, we confirmed that a high expression of RHBDD2 in RC tumors after NRC treatment is associated with the development of local or distant metastases. The collected evidence positions RHBDD2 as a promising prognostic biomarker to predict the response to neoadjuvant therapy in patients with RC.
Subject(s)
Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Membrane Proteins/genetics , Rectal Neoplasms/therapy , Unfolded Protein Response/drug effects , Antimetabolites, Antineoplastic/pharmacology , Caco-2 Cells , Cell Adhesion/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Endoplasmic Reticulum Chaperone BiP , Fluorouracil/pharmacology , Focal Adhesion Kinase 1/genetics , Focal Adhesion Kinase 1/metabolism , Focal Adhesions/drug effects , HCT116 Cells , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Humans , Lymphatic Metastasis , Membrane Proteins/metabolism , Neoadjuvant Therapy/methods , Paxillin/genetics , Paxillin/metabolism , Protein Binding , Rectal Neoplasms/genetics , Rectal Neoplasms/metabolism , Rectal Neoplasms/pathology , Signal Transduction , Transcription Factor CHOP/genetics , Transcription Factor CHOP/metabolism , eIF-2 Kinase/genetics , eIF-2 Kinase/metabolismABSTRACT
El tejido mamario tiene su origen hacia la cuarta semana del desarrollo fetal, aparecen engrosamientos ectodérmicos que se extienden a ambos lados desde las futuras axilas hasta la región inguinal, constituyendo las «líneas mamarias o lácteas». Durante la embriogénesis se produce una regresión espontánea de este tejido, a excepción del situado en la región torácica que da lugar a las mamas en el adulto. La regresión mamaria permite conservar solo una glándula a cada lado de la región pectoral. Cuando se produce un fallo en la regresión, se condiciona el desarrollo de estructuras mamarias ectópicas, las cuales tienen una presentación clínica variable. El caso de una mujer de 41 años, que presentó una tumoración inguinal derecha de un año de evolución, con crecimiento acelerado en los últimos meses. La biopsia confirmó que se trataba de una proliferación epitelial glandular benigna
The breast tissue originated in the fourth week of foetal development, comprising ectodermal thickening extending on both sides from the armpits to the inguinal region, i.e. the milk lines. During embryogenesis, spontaneous regression of this tissue occurs, except tissue located in the thoracic region, which gives rise to breast tissue in adults. Breast regression preserves only one gland on each side of the chest. Breast regression impairment leads to the development of ectopic breast tissue, the clinical presentation of which varies widely. We report the case of a 41-year-old woman who presented a right inguinal tumour of one year of development, with rapid growth in recent months. The biopsy confirmed that it was a benign glandular epithelial proliferation
Subject(s)
Humans , Female , Adult , Choristoma/pathology , Mammary Glands, Human/pathology , Inguinal Canal/pathology , Diagnosis, DifferentialABSTRACT
El carcinoma de células escamosas de tiroides (CCET) es un tumor infrecuente y agresivo. Su etiología es incierta. Ante la presencia de carcinoma escamoso en la glándula tiroides debe excluirse la posibilidad de infiltración de un tumor originado en una estructura adyacente o de metástasis de otros carcinomas. El tratamiento de elección es la cirugía radical. La mayoría de los pacientes fallecen antes del año debido a progresión local de la enfermedad. Presentamos el caso de un paciente con una masa tiroidea, con diagnóstico histológico de carcinoma escamoso (con inmunohistoquímca negativa para tiroglobulina, TTF1 y calcitonina y positiva para p63 y citok5). Los estudios clínicos, endoscópicos y radiológicos excluyeron otros sitios de origen de carcinoma escamoso. Fue tratado con quimio y radioterapia, falleciendo por progresión local luego de 9 meses.
Primary squamous cell thyroid carcinoma (PSCTC) is a rare and aggressive tumor of uncertain origin. When squamous carcinoma is diagnosed, it is mandatory to exclude the possibility of primary tumor arising from an adjacent structure or representing metastases from a primary growth elsewhere. Aggressive surgical resection is the treatment of choice. However, the prognosis is poor, with a median survival of less than a year. Death is usually secondary to progression of local disease. We report a case of a patient presenting with a thyroid mass; biopsy was consistent with squamous cell carcinoma. On immunohistochemistry tumor cells were negative for TTF1, thyroglobulin and calcitonin. Cancer cells were positive for p63 and citok5. Extensive workup excluded the possibility of extrathyroid origin. The patient was treated with chemoradiotherapy; he died 9 months later due to local progression.
Subject(s)
Humans , Male , Aged , Thyroid Neoplasms/diagnosis , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/physiopathology , Carcinoma, Squamous Cell/therapy , Diagnosis, DifferentialABSTRACT
Signet ring cell lymphoma is a rare neoplasm characterized by large, vacuolated and clear cells mimicking mucin-producing adenocarcinoma. It is localized in nodal and extranodal sites. A case of a 59 years old male, with a diffuse lymphoma signet ring cell type localized on oropharyngeal mucosa is reported. The histopathology study showed signet ring cells and the immunophenotype was: vimentine(+), CD45(+), CD20(+), Ig M(+), Kappa chain(+) and high index proliferative activity of neoplastic cells (Ki 67:70%). After a review of the literature and previous reports, we could not find a similar case in this anatomic site. The patient had a unfavourable clinical course and died two months after the diagnosis without receiving any treatment.
El linfoma de células en anillo de sello es una neoplasia poco frecuente, caracterizada por la presensenciade grandes células de citoplasma vacuolado, claro, similar a los encontrados en adenocarcinomasmucosecretantes. Se ha descripto en ganglios linfáticos y tejidos extralinfáticos. Se presenta el casode un paciente varón de 59 años con linfoma de células en anillo de sello localizado en pared lateral de orofaringe.Esta localización creemos que no ha sido descripta anteriormente. La histología mostró células en anillo de sello y el inmunofenotipo tumoral fue: vimentina, CD45, CD20, Ig M y cadenas kappa positivos, siendo la fracción de crecimiento tumoral alta (Ki 67:70%). El paciente evolucionó desfavorablemente y falleció a los dosmeses del diagnóstico sin recibir tratamiento.
Subject(s)
Humans , Male , Middle Aged , Adenocarcinoma, Mucinous/pathology , Carcinoma, Signet Ring Cell/pathology , Lymphoma, B-Cell/pathology , Oropharyngeal Neoplasms/pathology , Diagnosis, Differential , Treatment OutcomeABSTRACT
Signet ring cell lymphoma is a rare neoplasm characterized by large, vacuolated and clear cells mimicking mucin-producing adenocarcinoma. It is localized in nodal and extranodal sites. A case of a 59 years old male, with a diffuse lymphoma signet ring cell type localized on oropharyngeal mucosa is reported. The histopathology study showed signet ring cells and the immunophenotype was: vimentine(+), CD45(+), CD20(+), Ig M(+), Kappa chain(+) and high index proliferative activity of neoplastic cells (Ki 67:70%). After a review of the literature and previous reports, we could not find a similar case in this anatomic site. The patient had a unfavourable clinical course and died two months after the diagnosis without receiving any treatment.(AU)
El linfoma de células en anillo de sello es una neoplasia poco frecuente, caracterizada por la presensenciade grandes células de citoplasma vacuolado, claro, similar a los encontrados en adenocarcinomasmucosecretantes. Se ha descripto en ganglios linfáticos y tejidos extralinfáticos. Se presenta el casode un paciente varón de 59 años con linfoma de células en anillo de sello localizado en pared lateral de orofaringe.Esta localización creemos que no ha sido descripta anteriormente. La histología mostró células en anillo de sello y el inmunofenotipo tumoral fue: vimentina, CD45, CD20, Ig M y cadenas kappa positivos, siendo la fracción de crecimiento tumoral alta (Ki 67:70%). El paciente evolucionó desfavorablemente y falleció a los dosmeses del diagnóstico sin recibir tratamiento.(AU)
