Expression of EGF receptors in canine prostate with proliferative inflammatory atrophy and carcinoma / Expressão de receptores EGF na próstata canina com atrofia inflamatória proliferativa e carcinoma

ABSTRACT: Gene expression of ErbB1 and ErbB2, and immunostaining of EGFR (Her1) and Her2 (c-erbB-2) were evaluated in this study to ascertain whether these receptors are involved in the evolution of canine premalignant and malignant prostatic lesions, as proliferative inflammatory atrophy (PIA) and prostatic carcinoma (PC). With regards to the intensity of EGFR immunostaining, there was no difference between normal prostatic tissue and tissues with PIA or PC. In relation to Her2 immunostaining, there were differences between normal prostatic tissue and those with PIA and PC, as also differences between prostates with PIA and PC. There was no correlation between EGFR and Her2 immunostaining. ErbB1 gene product was detected in two normal tissue samples, in one with PIA, and in all samples with PC. ErbB2 mRNA was recorded in two canine samples with PIA, in all with PC, but was not detected in normal prostatic tissue. It was concluded that EGFR and Her2 play roles in canine PIA and PC, suggesting that those receptors may be involved in canine prostatic carcinogenesis.

RESUMO: A expressão gênica de ErbB1 e ErbB2 e a imunomarcação de EGFR (Her1) e Her2 (c-erbB-2) foram avaliadas para verificar o envolvimento desses receptores em lesões pré-malignas e malignas da próstata canina, como a atrofia proliferativa inflamatória (PIA) e o carcinoma prostático (PC). Em relação à intensidade de imunomarcação para EGFR, não houve diferença entre o tecido prostático normal e com PIA e PC. Em relação a Her2, observou-se diferença de imunomarcação entre o tecido prostático normal e aqueles com PIA e PC e entre os com PIA e PC. Não houve correlação entre EGFR e Her2. O gene ErbB1 foi detectado em duas amostras normais, uma de PIA e em todas as amostras de PC. O gene ErbB2 foi detectado em duas amostras de PIA e em todas as amostras de PC, não sendo detectado no tecido prostático normal. Conclui-se que EGFR e Her2 atuam nas lesões de PIA e PC, sugerindo o envolvimento destes na carcinogênese da próstata canina.

Efectos del bloqueo del sistema EGF/EGFR sobre la cicatrización de las heridas en pacientes oncológicos / Effects of the blockade of EGF/EGFR system on wound healing cancer patients

La administración de drogas que bloquean el sistema del factor de crecimiento epidérmico y su receptor ha demostrado efectos beneficiosos en pacientes con tumores sólidos de origen epitelial. Cada día resulta más frecuente el uso de múltiples modalidades terapéuticas para combatir estos tumores, las cuales incluyen la asociación de agentes blanco y cirugía. Los agentes que actúan sobre dicho sistema pudieran causar trastornos de la cicatrización al bloquear vías del sistema que también intervienen en la cicatrización de las heridas. El objetivo de este artículo es revisar y comentar acerca del conocimiento de la relación entre el uso de las drogas anti-EGF/EGFR y los trastornos en la cicatrización de las heridas. La búsqueda bibliográfica se realizó en PubMed y Google (solo en español e inglés) y se tuvo en cuenta cualquier publicación encontrada hasta enero del 2014. Se incluyeron los anticuerpos monoclonales cetuximab, panitumumab y nimotuzumab; las pequeñas moléculas erlotinib y gefitinib y las vacunas terapéuticas contra el cáncer CIMAvax EGF y HER-1. Se hace especial énfasis en los biofarmacéuticos nimotuzumab, CIMAvax EGF y HER-1; producidos en el Centro de Inmunología Molecular, La Habana, Cuba, debido a su amplio uso en Cuba y otros países de América Latina. No se encontraron evidencias de relación entre el uso de estos productos y la aparición de trastornos en la cicatrización de las heridas. Dado que los tratamientos anti-EGF/EGFR también inhiben la proliferación celular que induce el drenaje de las heridas y la migración celular inducida por las radiaciones, se sugiere que el tratamiento anti-EGF/EGFR no debe suspenderse, ni antes ni después de la cirugía y sus posibles efectos deben ser vigilados. Obviamente, se necesitan ulteriores investigaciones por parte de los farmacólogos no clínicos y clínicos, oncólogos clínicos y cirujanos oncológicos para entender mejor los procesos fisiopatológicos de cicatrización en los cánceres de origen epitelial(AU)

The use of blocking drugs for epidermal growth factor and its receptor system has shown beneficial effects in patients with solid tumors of epithelial origin. It is increasingly common to use a multi-modal treatment approach towards solid tumors, often including the association of target agents and surgical resection. Some target agents can impair wound healing or cause increasing risk of perioperative complications if they block system pathways that may intervene in wound healing. The objective of this paper was to review and comment on the existing knowledge about the relationship between the use of anti-EGF/EGFR drugs and the disorders in wound healing. Citations from PubMed and Google (English and Spanish languages only) regardless of the date of publication were reviewed to identify potentially useful articles until January 2014. Monoclonal antibodies cetuximab, panitumumab, nimotuzumab; the small molecules erlotinib and gefitinib, and the therapeutic cancer vaccines called CIMAvax EGF and HER-1. Special emphasis was made on biopharmaceuticals nimotuzumab, CIMAvax EGF and HER-1, all of them produced at the Center of Molecular Immunology, Havana, Cuba, because of their extensive use in Cuba and many Latin-American countries. No evidence of association between the use of these products and the occurrence of complications in wound healing was found. Given that the anti-EGF/EGFR treatments also inhibit the tumor cell proliferation that wound drainage induces and the radiation-induced cell migration, it is suggested that that the administration of this kind of drugs should be kept before and after the surgery and consequently, its possible effects must be under surveillance. Obviously, non-clinical and clinical pharmacologists, clinical oncologists and surgeons need further researches for better understanding the pathophysiological wound healing processes in epithelial cancers(AU)

Investigação das alterações moleculares nos receptores de fator de crescimento epidermal (HER-1 e HER-2) e da proteína P16 em carcinoma de células escamosas de língua e assoalho de pacientes jovens e adultos / Investigation of the molecular receptors epidermal growth factor (HER-1 and HER-2) and P16 protein in squamous cell carcinoma of the tongue and floor of young adult patients

O carcinoma de células escamosas (CCE) tem aumentado em pacientes jovens, principalmente em língua, correspondendo a 6% de todos os cânceres bucais. Sugere-se que essa neoplasia maligna seja uma doença distinta da que ocorre em pacientes mais velhos, com etiologia e progressão clínica particulares. Os receptores da família HER apresentam um importante papel na patogênese e progressão do CCE, sendo relevante a identificação de alterações no gene e na expressão das proteínas relacionadas ao CCE bucal...O CCE em pacientes jovens acomete mais a língua e não tem predileção pelo sexo masculino, estando o etilismo menos associado a esse grupo de pacientes em relação aos adultos. A imunopositividade observada para os anticorpos para HER-1 e p16 demonstra a participação dessas proteínas na carcinogênese dos CCE de língua e assoalha de boca. A presença de mutações nas regiões hot spots do gene HER-1 reforça a participação desse gene no desenvolvimento CCE de língua e assoalho em pacientes jovens. Futuras investigações são sugeridas nessa linha de pesquisa, para avaliar proteínas envolvidas na via de sinalização do HER-1, bem como nos casos p16 positivos, a presença do vírus HPV.

The Survival Analysis of Immunohistochmically Defined Basal and Luminal Subtype of Breast Cancer

PURPOSE: DNA microarray studies of breast cancer have identified distinct subtypes showing different survivals. The results of DNA microarray revealed the HER2 negative and estrogen receptor (ER) negative subtypes, which were designated as basal or basal-like subtype. The basal subtype can not be manipulated by trastuzumab or the selective estrogen receptor modulator (SERM), but DNA microarrays are not perform in clinical practice. We classified invasive ductal carcinoma (IDC) into the luminal, HER2, basal and negative groups using an immunohistochemical method and evaluated the usefulness of the method in clinical practice. METHODS: A retrospective analysis was conducted using the medical records of 295 patients, diagnosed with IDC of the breast, who subsequently underwent a mastectomy between January 1992 and September 2004. A tissue microarray was constructed and immunohistochemical studies performed for HER2, ER, HER1, c-kit and CK5/6. The breast cancers were divided into four subtypes, which included the HER2 positive, luminal, basal and negative subtypes. The basal subtype was characterized by HER2 negative, ER negative and positive for one of HER1, c-kit or CK5/6. Only the ER positive subtype was designated as a luminal subtype. The survival rates were calculated using the Kaplan Meier methods. RESULTS: The 5 year survival rates of the HER2 positive, luminal and basal subtypes were 80.4, 86.8 and 73.8%, respectively (P=0.1274). The basal subtype was predominant among the patients with poorly differentiated carcinomas (P=0.000). The 5 year overall survival of the basal subtype was lower than that of luminal (P=0.049); the prognosis was also poor in those with an age less than 35 years old, premenopausal and lymph node metastasis. CONCLUSION: The basal subtype was associated with a high histologic grade, and also showed significantly worse prognosis then the luminal subtype, especially in those patients with an age less than 35, premenopausal and lymph node metastasis. The immunohistochemical assay for the basal subtype was helpful in detecting patients with a poor prognostic.