Dissociated invasively growing cancer cells with NF-kappaB/p65 positivity after radiotherapy: a new marker for worse clinical outcome in rectal cancer? Preliminary data
Abstract
Objectives: Nuclear factor-kappaB (NF-kappaB), especially p65 subunit, seems to be associated with origin and progression of cancer. The aim of the study was to determine expression of NF-kappaB/p65 in rectal cancer patients before and after radiotherapy as well as to assess the relationship between NF-kappaB/p65 expression, other tumor characteristics, and disease progression.
Further aim was to evaluate whether expression of NF-kappaB/p65 in tumor tissue may serve as a predictive marker of patient outcome. Patients and methods Twenty-five patients with rectal cancer undergoing pre-operative radiotherapy were included in the study.
Unirradiated rectal cancer specimens were obtained from diagnostic colonoscopy. Irradiated rectal cancer specimens were obtained from surgically removed part of the rectum with the tumor.
NF-kappaB/p65 expression was determined by immunohistochemistry. Results Cytoplasmic positivity in cancer cells and nuclear positivity in lymphocytes were detected.
In post-radiotherapy specimens single tumor cells or small clones of them deeply infiltrating the wall of the rectum, that were characterized by high NF-kappaB/p65 expression, were found. Patients with presence of these cells in post-radiotherapy specimens have worse clinical outcome in terms of overall survival and disease-free interval.
Conclusion While the NF-kappaB/p65 positive staining of the epithelial cells did not have any clinical implications in this study, it may be of clinical significance in the future. Residual invasively growing cancer cells with high NF-kappaB/p65 positivity found in specimens after radiotherapy and surgery may be used to find what patients have a worse outcome.
Thus, patients being at risk of cancer progression and requiring more aggressive anti-cancer therapy may be identified.