Estudio del anticuerpo DOG1 en el diagnóstico de tumores del estroma gastrointestinal - GIST

Abstract

Los tumores del estroma gastrointestinal (GIST) poseen mutaciones en los genes del receptor de la tirosín quinasa (RTKs) KIT y PDGFRA. La posibilidad de bloquear esta actividad ha significado una nueva esperanza terapéutica. El diagnóstico de GIST recae en la expresión inmunohistoquímica del c-KIT, pero un 4-15% son c-KIT negativos (aún en presencia de mutación), y sin embargo estos pacientes podrían beneficiarse del tratamiento con inhibidores tirosín quinasa (TKIs).El DOG1 es un nuevo anticuerpo cuya sensibilidad y especificidad parece ser superior o igual a la del c-KIT. El objetivo de este trabajo es evaluar la sensibilidad (Se) y especificidad (Sp) de DOG1 en GIST de tipo usual (c-KIT positivos), de tipo inusual (c-KIT negativos) y frente a otros tumores fusocelulares mesenquimales, y comparar la validez diagnóstica del DOG1 frente al c-KIT.Estudiamos 40 GIST, 39 c-KIT positivos y un c-KIT negativo. Se realizó un panel inmunohistoquímico con los anticuerpos: c-KIT, CD34, actina músculo liso, DOG1 y S100, en los GIST como en siete tumores fusocelulares.La Se y Sp de GIST para DOG1 fue del 100 y 97,5% para c-KIT. La inmunoreactividad para DOG1 en todos los tumores fusocelulares fue negativa. La validez diagnóstica de DOG1 y C-KIT fue similar a la hora de detectar GIST y no GIST. DOG1 es un marcador específico y sensible para el diagnóstico y diagnóstico diferencial de GISTs (es capaz de detectar algunos GIST sin mutación en RTK). El DOG1 debería de formar parte del panel inmunohistoquímico para el diagnóstico de GIST.Palabras clave. GIST. DOG1. aBstractGatrointestinal stromal tumours (GIST) harbour oncogenic mutations in tyrosin kynases receptors (RTKs) including KIT and PDGFRA. The inhibition of this activity has been regarded as the primary target for the treatment of these patients. Diagnosis of GIST relies on c-KIT inmunoreactivity; however there is a 4-15% of GISTs that are C-KIT negative which may lead to underdiagnosis of GISTs and possible withholding of therapy.The novel gene DOG1 has been found overexpressed in GISTs and has potential as a diagnostic marker for GISTs showing even more sensitivity (Se) and specificity (Sp) than c-KIT for the diagnosis of these tumors. In this study we compared the (Se) and (Sp) of DOG1 in typical and atypical GISTs (c-KIT positive or negative) with c-KIT and other mesenchymal neoplasms in the differential diagnosis of GISTs We examined 40 GIST (39 showed inmunoreactivity for c-KIT and one was c-KIT negative) and another seven fusiform tumors. An inmunohistochemical panel was performed with c-KIT, CD34, smooth muscle actin, DOG1 and S100 antibodies on both types of neoplasms.The overall Se and Sp of DOG1 and KIT in GISTs were nearly identical: 100 and 97,5%. Negativity for DOG1 was observed in all fusiform mesenchymal neoplasms.DOG1 is highly expressed in GIST and its expression seems quite specific for these tumours when the differential diagnosis includes another mesenchymal neoplasms.DOG1 should be added to the diagnostic panel evaluating GISTs.

Expression of ANO1/DOG1 is associated with shorter survival and progression of breast carcinomas

“…ANO1 is also known as DOG1, TMEM16A, ORAOV2 and TAOS2 [ 2 ]. In clinical oncology, the expression of ANO1/DOG1 was considered to have diagnostic specificity for determining which tumor is gastrointestinal stromal tumor to consider targeted therapy [ 3 ]. However, its biologic characteristic as a calcium-activated chloride channel [ 1 , 4 , 5 ] suggests that ANO1/DOG1 might be involved in various pathophysiologic statuses [ 2 ].…”