Correlation of expression of pro-apoptotic proteins bax and bak with lymph node metastasis in colonic adenocarcinoma
e15042 Background: Colon cancer has been associated with disturbances in the regulation of apoptosis. Down regulation of Bax and Bak, members of the Bcl-2 family, are associated with tumor metastasis. Here we investigate how these two pro-apoptotic markers correlate with lymph node (LN) metastasis in colonic adenocarcinoma (CA). Methods: Paraffin-embedded sections from 100 cases of CA were constructed in tissue microarrays and subjected to immunohistochemistry (IHC) using the ABC method and antibodies for Bax and Bak. The IHC score is the product of intensity and percentage of positively stained cells, and ranged between 0 and 9. The total scores were divided into categories of “2 or less” and “3 or more.” These were than correlated with LN metastasis. Results: For Bax, 88 tumors were available while Bak was present in 100 tumors. In scoring Bax, 67 tumors had a score of ≤2 and 21 had a score of ≥3. Within the ≤2 category, 23 of 67 (34%) tumors had no LN metastases while 15 of 21 (71%) in the ≥3 category had no metastasis (p= 0.0029). For Bak staining, 23 had a score of ≤2 and 77 had a score of ≥3. Five of 23 (22%) tumors with a score ≤2 had no metastases and 35 of 77 (46%) with score ≥3 had no metastases (p= 0.0427). The LOGISTIC Procedure was used to show that a patient with a ≥3 Bax score has a 4.78 times odds ratio (95% C.I.: 1.64- 13.98) of having no metastases while a patient with a ≥3 Bak score has a 3 times odds ratio (95% C.I.: 1.01- 8.90) of having no metastases. Conclusions: We show correlation of the pro-apoptotic proteins Bax and Bak with decreased lymph node metastasis in CA. The findings suggest a role for these markers in predicting stage and patient survival in colonic adenocarcinoma. No significant financial relationships to disclose.