Rafael Yus Ramos

Proteínas de choque térmico en el estrés quirúrgico: toracotomía frente a herniorrafia

Resumen Introduccion El estres quirurgico y anestesico libera citocinas y especies reactivas de oxigeno capaces de inducir la sintesis de las proteinas de choque termico (HSP), proteinas con propiedades inmunomoduladoras y potentes autoantigenos. Se pretende estudiar la biologia de las HSP70 intraleucocitarias y la posible respuesta autoinmunitaria desencadenada por 2 tipos diferentes de agresion quirurgica. Pacientes y metodo Grupo I: grupo control con 3 pacientes. Grupo II: grupo de toracotomia, cirugia radical y anestesia general, con 6 pacientes. Grupo III: grupo de cirugia poco radical, herniorrafia y raquianestesia, con 4 pacientes. Se analizaron HSP70 intraleucocitarias y anticuerpos anti-HSP70i, antes (T0) y 24 h despues de la intervencion (T1). Resultados El 50% de los pacientes expuestos a toracotomia presento un significativo descenso del contenido de HSP intracelulares en el postoperatorio, simultaneo al incremento de los valores de autoanticuerpos anti-HSP70i. El grupo de pacientes expuestos a herniorrafia con anestesia locorregional no desarrollo respuesta autoinmunitaria. Conclusiones En el limitado numero de pacientes estudiados, la enfermedad neoplasica y la mayor agresividad de la toracotomia parecen asociarse con una reduccion de las HSP en comparacion con lo que sucede en los pacientes mas sanos a los que se les realizo una herniorrafia. La disminucion de las HSP fue simultanea a la presencia de autoanticuerpos circulantes. No se observo relacion entre el estado inmunitario previo y la respuesta autoinmunitaria en el postoperatorio inmediato.

KIT, DOG1, PDGFR, and IGFR1 gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients.

10047 Background: There are scarce and controversial findings published on KNGL series. One of the largest analyzing 26 KNGL found two distinct subsets according to immunostaining (IS): DOG1+ cases were gastric with PDGFRA mutations and DOG1- cases were gastric or intestinal both alike and usually wild type. We analyzed expression of genes known to be implicated in GIST as well as miRNA221/222 (negative regulators of KIT) to attempt a better characterization of KNGL and to assess their prognostic value in a KNGL series of 32 patients. METHODS The expression level of KIT, PDGFRA, DOG1, IGF1R, miRNA-221 and miRNA-222 was determined by qRT-PCR. We also analyzed the KIT and PDGRA mutations, DOG1 IS along with clinical and pathological data. Differences in metastases free and overall survival were calculated for the various prognostic factors using Log-rank test. RESULTS The M/F rate was 16/16 and the median age was 62 y. With a median follow-up of 92 months, 14 events of metastases were registered. Hierarchical cluster analyses obtained from gene expression data identified two distinct groups: Group I, had an overexpression of KIT, DOG1 and PDGFRA, and underexpression of IGF1R; with predominance of epitheliod gastric cases, DOG1 + IS and PDGFRA mutations. On the contrary, group II had overexpression of IGF1R and underexpression of KIT, DOG1 and PDGFRA; most cases were non-gastric with DOG1 - IS and KIT mutated or wild type. Group II had a significant worse prognosis for both metastasis free (p= 0.028) and overall survival (p=0.013). The expression of miRNAs was lower in a subset of 9 cKIT + cases compared with this KNGL series (p =0.057 for miRNA221 and p<0.001 for miRNA222). Interestingly, the overall survival was significantly worse in cases with higher expression of miRNA221 (p =0.028) or miRNA222 (p=0.014) in the KNGL series. CONCLUSIONS Our results identify the existence of two distinct subsets of KNGL cases also at gene expression level with a different prognostic value. Increased levels of miRNA-221/222 could explain the absence of protein expression of most of such cases. Finally, the fact of worse survival associated to higher miRNA 221/222 expression level deserves further investigation.