B. Trac2, X. Ding3, A. McHenry2, J. Eberhardt4, T. Saclarides1, D. Hayden1 1Rush University Medical Center,Department Of General Surgery,Chicago, IL, USA 2Loyola University Medical Center,Stritch School Of Medicine,Maywood, IL, USA 3Loyola University Medical Center,Department Of Pathology,Maywood, IL, USA 4Loyola University Medical Center,Department Of General Surgery,Maywood, IL, USA
Introduction: Sex-determining Region Y box 9 (SOX9) has been shown to play a fundamental role in epithelial-mesenchymal transition (EMT) as well as be dysregulated in colorectal cancer. Its role in carcinogenesis remains controversial since SOX9 has been associated with both positive and negative prognostic factors in multiple cancers.
Methods: Sections from both normal and cancerous tissue were taken before and after radiation in 25 patients with locally advanced rectal cancer who received neoadjuvant chemoradiation followed by surgery. SOX9 expression was evaluated by immunohistochemistry using a 4-tier grading system for intensity of expression (0=none, 1=low, 2=moderate, 3=high) and percentage of SOX9-positive cells. Demographics, tumor characteristics and outcomes were extracted from medical records and SPSS (Chicago, IL) was used for statistical analysis.
Results: In this study population, mean age was 60.4 (32-72), 80% were male and the majority of patients were Caucasian (76%). 92% of patients had at least T3 tumors and 68% had stage III disease. Mean maximal diameter of tumor pre-treatment was 4.95 cm (3-8) and post-radiation was 2.79 (0.4-5.3). Down-staging occurred in 15 (60%) patients, but only 2 (8%) had complete pathologic response. 6 (24%) patients had positive nodes found after surgery.
In cancer specimens, 96% were graded as moderate or high expression before treatment; 88% after radiation. 91.7% of cells were SOX9+ before radiation, which decreased to 66.7% after radiation. The majority of specimens (68%) showed decrease in expression intensity and %SOX9 positivity. Before radiation, patients with higher SOX9 % positivity were more likely hypertensive (p=0.037) and they were more likely to be male, diabetic and previous smoker (p=0.05, 0.04, 0.015, respectively) if higher SOX9 positivity after radiation. % SOX9+cells and moderate or high expression were both associated with complete pathologic response (p=0.008). Decreased intensity was associated with postoperative tumor size (p=0.005). Although not statistically significant, decrease in percent positivity and intensity after radiation both trended toward significance for distant recurrence (p=0.07). SOX9 expression was not associated with other tumor characteristics or oncologic outcomes.
Conclusion: Our findings indicate that SOX9 % positivity and moderate or high intensity of expression in rectal cancer specimens decrease after radiation. Oncologic outcomes appear to be improved when intensity of expression and percent positivity remain elevated, for example, in complete pathologic response. When expression decreases after radiation, distant recurrence and larger post-radiation tumor size are more common. Although its role remains controversial, our findings suggest that SOX9 may be an important marker and potential target for tumor response and oncologic outcomes for rectal cancer after radiation.