BCCIP as a prognostic marker for radiotherapy of laryngeal cancer.
BACKGROUND
Recent studies have shown that BCCIP (BRCA2 and CDKN1A interacting protein) is essential for maintaining the transactivation activity of wild type p53. We analyzed the expression of BCCIP and p53 in a cohort of laryngeal cancer treated with radiotherapy and assessed whether BCCIP and p53, alone or in combination, would correlate with local control and overall survival.


METHODS
One hundred twenty-three patients treated between 1975 and 2000 for early stage (stages I and II) squamous cell carcinoma of the larynx were included in the study. Treatment consisted of radiation therapy (RT) with standard fields and fractionation to a median dose of 66Gy. Tissue was collected from pre-RT biopsies and constructed in a tissue microarray, and BCCIP expression and p53 expression were determined using immunohistochemistry.


RESULTS
Loss of expression of BCCIP in combination with normal p53 (negative p53 staining) was associated with local recurrence (RR 2.04; 95% CI 0.99-4.56, p=0.05) and poor overall survival (RR 2.09; 95% CI 1.21-4.00, p=0.008) compared to patients who did express BCCIP. Expression of BCCIP or p53 alone was not found to be independently associated with benefits in local control or overall survival.


CONCLUSIONS
This study provides clinical evidence that BCCIP contributes to outcomes in patients with laryngeal cancer treated with RT. This benefit may be a result of increased radiosensitivity in patients who have functional BCCIP and p53. These data may be used to identify sub-groups of laryngeal cancer patients who are more likely to be cured with radiotherapy.
Rewari
Amar
A
Yale University School of Medicine, New Haven, CT, USA.
Lu
Huimei
H
Parikh
Rahul
R
Yang
Qifeng
Q
Shen
Zhiyuan
Z
Haffty
Bruce G
BG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002135:Calcium-Binding Proteins / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000401:mortality / Q000532:radiotherapy*; D018797:Cell Cycle Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
C415366:BCCIP protein, human; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53