Expression of nuclear transcription factor kappa B in locally advanced human cervical cancer treated with definitive chemoradiation

Abstract

Purpose: Nuclear factor kappa B (NF-κB), a transcriptional factor that has been shown to be constitutively active in cervical cancer, is part of an important pathway leading to treatment resistance in many tumor types. The purpose of our study was to determine whether expression of NF-κB in pretreatment specimens and specimens taken shortly after treatment initiation correlated with outcome in cervical cancer patients treated with definitive chemoradiation.

Methods and materials: Eighteen patients with locally advanced cervical cancer were enrolled in a study in which cervical biopsy specimens were obtained before radiation therapy and 48 h after treatment initiation. Matched biopsy specimens from 16 of these patients were available and evaluated for the nuclear expression of NF-κB protein by immunohistochemical staining.

Results: After a median follow-up of 43 months, there were 9 total treatment failures. Nuclear staining for NF-κB was positive in 3 of 16 pretreatment biopsy specimens (19%) and 5 of 16 postradiation biopsy specimens (31%). Pretreatment expression of NF-κB nuclear staining correlated with increased rates of local-regional failure (100% vs. 23%, p = 0.01), distant failure (100% vs. 38%, p = 0.055), disease-specific mortality (100% vs. 31%, p = 0.03), and overall mortality (100% vs. 38%, p = 0.055).

Conclusions: Our data suggest that pretreatment nuclear expression of NF-κB may be associated with a poor outcome for cervical cancer patients treated with chemoradiation. Although these data require validation in a larger group of patients, the results support the continued study of the relationship between NF-κB and outcome in patients treated for carcinoma of the cervix.

Figure 1

a. Example of positive nuclear staining of NF-κB. b. Example of negative nuclear staining of NF-κB.