Background: Glutathione S-transferases (GSTs) are an enzyme family responsible for the metabolism of toxins and carcinogens in the phase II detoxification pathway. Among the 5 alpha class isoforms, GSTA1 and GSTA3 are involved in metabolizing several active carcinogenic substrates generated from benzo-[a]-pyrene mainly found in grilled meats and burnt coal. The expression of GSTA1 and GSTA3 in gastrointestinal (GI) tract may be implicated with cancer development associated with the intake of xenobiotic substances.

Methods: Formalin-fixed and paraffin-embedded tissue cores of esophagus (190), stomach (180), small intestine (372), colon (120) and rectum (142) were stained with a multiplex tyramide-immunofluorescence (T-IMF) technique for the simultaneous demonstration of cytokeratin AE1/AE3, GSTA1 and GSTA3. The tissue types range from normal to cancer progression spectrum. All tissue cores were screened for AE1/AE3 expression to confirm the epithelial cell lineage before scoring for GSTA1 and GSTA3 positivity. A p-value <0.05 by Chi-squared test is considered significant.

Results: T-IMF is useful in studying the interaction of multi-markers in a single slide. This technique is superior to chromogenic immunohistochemical application in multi-color presentation. This highly sensitive and handy technique will save multiple sectionings and precious tissues. We found a significant down-regulation of two alpha class GSTs in the malignancies of GI tract (Table 1).

Table 1. Positive percentages of glutathione S-transferases markers

Marker Esophagus Stomach Small intestine Colon Rectum 
 
GSTA1 41% 24% 99% 40% 90% 15% 22% 3% 43% 21% 
p-value 0.0603 <0.0001 <0.0001 0.001 0.0194 
GSTA3 78% 35% 99% 54% 96% 64% 100% 39% 88% 40% 
p-value <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 
Abbreviation: N= normal; M= malignant 
Marker Esophagus Stomach Small intestine Colon Rectum 
 
GSTA1 41% 24% 99% 40% 90% 15% 22% 3% 43% 21% 
p-value 0.0603 <0.0001 <0.0001 0.001 0.0194 
GSTA3 78% 35% 99% 54% 96% 64% 100% 39% 88% 40% 
p-value <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 
Abbreviation: N= normal; M= malignant 

Conclusion: The differential expression of these detoxification enzymes in normal epithelium vs GI cancer may shed some light on their role in protecting normal tissue from cancer development. This finding may provide a potential target for the development of intervention strategies against GI cancer. Further investigations will be conducted to decipher the mechanism underlying this observation.

Citation Format: Victor Wan-San Ma, Goretti Hoi-Yan Cheung, Eunice Yuen-Ting Lau, William Chi-Shing Cho. Xenobiotic detoxification enzymes and cancer risk: A multiplex immunofluorescence detection of AE1/AE3, GSTA1 and GSTA3 in the tissue microarrays of gastrointestinal tract [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3597.