ABSTRACT
Autophagy is a host defensive mechanism responsible for eliminating harmful cellular components through lysosomal degradation. Autophagy has been known to either promote or suppress various cancers including colorectal cancer (CRC). KRAS mutation serves as an important predictive marker for epidermal growth factor receptor (EGFR)-targeted therapies in CRC. However, the relationship between autophagy and KRAS mutation in CRC is not well-studied. In this single-centre study, 92 formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients (42 Malaysian Chinese and 50 Indonesian) were collected and KRAS mutational status was determined by quantitative PCR (qPCR) (n=92) while the expression of autophagy effector (p62, LC3A and LC3B) was examined by immunohistochemistry (IHC) (n=48). The outcomes of each were then associated with the clinicopathological variables (n=48). Our findings demonstrated that the female CRC patients have a higher tendency in developing KRAS mutation in the Malaysian Chinese population (p<0.05). Expression of autophagy effector LC3A was highly associated with the tumour grade in CRC (p<0.001) but not with other clinicopathological parameters. Lastly, the survival analysis did not yield a statistically significant outcome. Overall, this small cohort study concluded that KRAS mutation and autophagy effectors are not good prognostic markers for CRC patients.
Subject(s)
Autophagy , Colorectal Neoplasms , Proto-Oncogene Proteins p21(ras)/genetics , Autophagy/genetics , Cohort Studies , Colorectal Neoplasms/genetics , Female , Humans , MutationABSTRACT
INTRODUCTION: Autophagy is a mechanism that degrades large damaged organelles and misfolded proteins to maintain the homeostasis in all cells. It plays double-faceted roles in tumourigenesis and prevention of various cancers. In our side observation of investigating the prognostic value of autophagy in colorectal cancer (CRC), we found high expression of autophagy proteins (LC3A, LC3B, and p62/SQSTM1) in the colonic ganglion cells. To our best understanding, this is the first paper reporting such finding. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) CRC tissues blocks were retrieved and confirmed by haematoxylin & eosin (H&E) staining. Immunohistochemistry (IHC) targeting autophagy proteins (LC3A, LC3B, and p62/SQSTM1) was then performed followed by pathological examination. RESULTS: All three autophagy proteins were present in both normal and tumour tissues of CRC patients. Interestingly, high expression of autophagy proteins in colonic ganglion cells was consistently seen regardless of tissue type (normal or cancer) or tumour site (caecum, ascending, transverse, descending, sigmoid colon and rectum). CONCLUSIONS: This work highlights the high autophagic activities in human colonic ganglion cells.
Subject(s)
Autophagy/physiology , Colon/metabolism , Neurons/metabolism , Colorectal Neoplasms/metabolism , Humans , Microtubule-Associated Proteins/metabolism , Sequestosome-1 Protein/metabolismABSTRACT
Three patients presenting with parotid, submandibular, and/or lymph node masses were subjected to fine-needle aspiration cytology. Smears showed dissociated and clustered endothelial cells, eosinophils, lymphocytes, and Warthin Finkeldey giant cells. In two cases a diagnosis of Kimura's disease was suggested from the FNA cytologic smears. In the third case the presence of mononucleate cells with prominent nucleoli led to a suspicion of Hodgkin's disease. Excision biopsy and histopathologic study established a diagnosis of Kimura's disease in all three cases.
