Expresion inmunohistoquimica e inestabilidad microsatelital en el sindrome de lynch / Immunohistochemical expression and microsatellite instability in Lynch syndrome

Las mutaciones de los genes MLH1 y MSH2 son frecuentemente implicadas en el síndrome de Lynch. La expresión inmunohistoquímica (IHQ) es una forma simple de selección para pruebas moleculares. Se analizó la IHQ de MLH1 y MSH2 en pacientes con síndrome de Lynch (16 casos) y pacientes menores de 50 años sin antecedentes familiares (25 casos). Se estudiaron 41 tumores de un grupo de pacientes (64% mujeres) de edad promedio 40.7 años (rango: 16-75). Se obtuvieron resultados concluyentes en 40 casos (97.6%). Dieciocho casos (45%) presentaron falta de expresión (MLH1 negativa: 11 casos; MSH2 negativa: 6 casos; MLH1 negativa y MSH2 negativa: 1 caso), con una incidencia significativamente mayor en pacientes con síndrome de Lynch (68.7% vs. 28%, p=0.01). Entre los casos esporádicos, 5 casos (20%) mostraron falta de expresión MLH1 y 2 casos (8%) con falta de expresión MSH2. La falta de expresión IHQ presentó una fuerte asociación con inestabilidad microsatelital alta (IMS): expresión normal: 5.9%, expresión negativa: 92.3%, P<0.0001. Los índices de sensibilidad y especificidad de la IHQ para detectar IMS fueron de 92.3% y 94.1% respectivamente. Los patrones de IHQ y de IMS no se relacionaron a ninguna característica histopatológica. En conclusión, el análisis inmunohistoquímico de las proteínas MLH1 y MSH2 fue altamente sensible y específico para detectar IMS y permitió identificar en un 45% de los casos la proteína alterada. El índice de falta de expresión IHQ entre los casos esporádicos diagnosticados antes de los 50 años justifica su implementación sistemática en este grupo de pacientes.

Mutation of the mismatch repair genes MLH1 and MSH2 account for the majority of the genetic abnormalities in Lynch syndrome. Immunohistochemical detection of their protein products is becoming an increasingly common method to detect these mutations. The aim of this study was to compare the expression of MLH1 and MSH2 by immunohistochemistry and its relationship with a group of clinical and histological variables in patients with known Lynch syndrome (n=16) and in cohort of young patients (less than 50 years) who did not meet Amsterdam criteria (n=25). The mean age was 40.7 and 64% were women. Conclusive results were obtained in 40 cases (97.6%). Eighteen cases (45%) showed abnormal expression of either MLH1 (11 cases) or MSH2 (6 cases) and both stains (1 case). Alteration of the normal staining pattern was seen more commonly in patients with Lynch syndrome than in the sporadic group (68.7% vs 28%, p=0.01). A significant correlation was obtained between abnormal protein expression and microsatellite instability (MSI): normal expression: 5.9%, lack of expression: 92.3%, p<0.0001. The sensitivity and specificity of the immunohistochemical to predict MSI were 92.3% and 94.1% respectively. Immunohistochemistry and MSI results did not correlate with any histopathological parameter. In conclusion, in our experience abnormal staining of MLH and MSH correlates strongly with the presence of MSI. In addition it appears that in our population a significant proportion of young patients (< 50 years old) demonstrate alterations in the mismatch repair gene products suggesting an important role of these molecules in tumorigenesis.

Testing of a new prototype surgical stapler that automates the rollover sleeve technique for venous anastomoses

The creation of successful vascular anastomoses is of primary importance in many surgical fields. Numerous attempts to automate this process have been made. These techniques have slowly gained acceptance, but their use is still limited. This report details feasibility testing of a new prototype stapler that automates the rollover sleeve technique for venous vascular anastomoses. Male and female mongrel dogs (n=7) (25-32 kg) were used. A segment of the right (n=5) or left (n=2) iliac vein was harvested for interposition grafts after the contra lateral side was transected. In each dog, two end-to-end venous anastomoses at the interposition grafts were performed. The standard anastomosis employed continuous mattress sutures. The experimental anastomosis was performed with a new prototype surgical stapler. The stapled anastomosis was proximal and the sutured was distal. In all experiments, it was possible to perform the experimental anastomosis with the stapler. Complications included two small leaks, one due to misfiring of a single pin in one experimental site. These leaks required suture reinforcement. One dog died of hemorrhage due to a slipped suture at the vein harvest site. One vein had thrombus seen at the sutured site although no technical abnormalities at either of the anastomoses could be found. After two weeks, grafts were inspected grossly and histologically. Healing appeared normal. There was a trend for less inflammatory cells infiltrating stapled sites; however, this was not statistically significant. The experiments demonstrate that this device can automate the rollover sleeve technique for venous anastomoses.