Alexandra Giatromanolaki1, Michael I Koukourakis2, Ioannis Georgiou3, Maria Kouroupi3, Efthimios Sivridis3. 1. Department of Pathology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis, Greece targ@her.forthnet.gr agiatrom@med.duth.gr. 2. Department of Radiotherapy/Oncology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis, Greece. 3. Department of Pathology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
Abstract
BACKGROUND: The current study examined the key proteins involved in autophagosome formation and their prognostic role in gastric cancer. MATERIALS AND METHODS: Paraffin-embedded tissues from 121 consecutive patients treated with surgery for gastric cancer were analyzed immunohistochemically for the expression of autophagic proteins microtubule-associated proteins 1A/1B light chain 3A and 3B (LC3A, LC3B) and beclin-1 (encoded by BECN1 gene). Assessment of proliferative index using the MIB1 monoclonal antibody (recognizing an epitope of the Ki-67 antigen, encoded by the MK167 gene) and correlations with histopathological [corrected]. RESULTS: Strong cytoplasmic expression was noted for all studied proteins, although to a varying proportion, the median percentage being 30% for LC3A, and 40% for LC3B and beclin-1. The median score of LC3A+ stone-like structures (SLS) was 0.2 (range 0-1) and the median proliferative index was 30% (range=0-95%). A significant association between LC3A, LC3B and beclin-1 expression was confirmed (p<0.01). SLS score was higher in tumors of the gastro-esophageal junction (p=0.009), and beclin-1 was overexpressed in intestinal-type tumors (p=0.001). High SLS score (p=0.008) was significantly related to poor prognosis, and this finding persisted in multivariate analysis (hazard ratio(HR)=2.01, p=0.003). CONCLUSION: Intense autophagic activity, as assessed by LC3A immunostaining and SLS quantification, is a strong prognostic marker in gastric cancer and can be useful for clinical application. Copyright
BACKGROUND: The current study examined the key proteins involved in autophagosome formation and their prognostic role in gastric cancer. MATERIALS AND METHODS:Paraffin-embedded tissues from 121 consecutive patients treated with surgery for gastric cancer were analyzed immunohistochemically for the expression of autophagic proteins microtubule-associated proteins 1A/1B light chain 3A and 3B (LC3A, LC3B) and beclin-1 (encoded by BECN1 gene). Assessment of proliferative index using the MIB1 monoclonal antibody (recognizing an epitope of the Ki-67 antigen, encoded by the MK167 gene) and correlations with histopathological [corrected]. RESULTS: Strong cytoplasmic expression was noted for all studied proteins, although to a varying proportion, the median percentage being 30% for LC3A, and 40% for LC3B and beclin-1. The median score of LC3A+ stone-like structures (SLS) was 0.2 (range 0-1) and the median proliferative index was 30% (range=0-95%). A significant association between LC3A, LC3B and beclin-1 expression was confirmed (p<0.01). SLS score was higher in tumors of the gastro-esophageal junction (p=0.009), and beclin-1 was overexpressed in intestinal-type tumors (p=0.001). High SLS score (p=0.008) was significantly related to poor prognosis, and this finding persisted in multivariate analysis (hazard ratio(HR)=2.01, p=0.003). CONCLUSION: Intense autophagic activity, as assessed by LC3A immunostaining and SLS quantification, is a strong prognostic marker in gastric cancer and can be useful for clinical application. Copyright
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