ERCC1 Expression, Gender and Leukocytosis as Prognostic Indicators in Advanced Stage Non-Small Cell Lung Carcinoma with Cisplatin-Based Chemotherapy?
G Luo, H Bui, N Patil, J Reynolds, N Karim, M Anderson, P Pathrose, A Mehta. VA Medical Center, Cincinnati, OH; University of Cincinnati, Cincinnati, OH
Background: Excision repair cross-complementation group 1 (ERCC1) plays a pivotal role in resistance of non-small cell lung cancer (NSCLC) to cisplatin-based chemotherapy. Evidence of hematopoetic growth factors (G-CSF) secreted by NSCLC is associated with the increased production of leukocytes. Some studies also show gender association with prognosis in NSCLC. Our aim was to evaluate ERCC1 expression, gender and leukocytosis as prognostic indicators in advanced stage NSCLC patients given cisplatin-based therapy.
Design: We retrospectively reviewed advanced stage NSCLC patients from the VAMC and University of Cincinnati from 1998-2007. Two pathologists independently reviewed the tissue sections for adequacy and selected 29 patients treated with cisplatin-based chemotherapy. IHC for ERCC1 (Mouse monoclonal ab- 8F1, Thermo Scientific, 1:200) was independently graded by 2 pathologists (0=absent; 1=weak, focal; 2=strong/diffuse). Baseline pre-treatment WBC counts were obtained from electronic medical records. Death dates were confirmed by contacting their physicians and hospice centers. ERCC1 reactivity and gender were correlated with overall survival (Cox proportional hazards model).
Results: Out of 29 patients (mean age=64; range: 42-84; 7 females (24%), 22 males (76%), 5 patients (17%) had leucocytosis (>11,000/L). ERCC1 expression was positive in 15/29 patients (52%). 67% of patients with positive ERCC1 expression showed leukocytosis. 7 patients, who survived >36 months (mean= 54 mths) did not express ERCC1. 7 patients with significantly shorter survival (mean=11 mths) strongly expressed ERCC1. ERCC1 negativity and female gender were significantly associated with longer overall survival (p=0.018 and 0.048 respectively). Leukocytosis trended towards shorter survival, without reaching statistical significance (p=0.58).
Conclusions: 1. Increased ERCC1 expression may predict shorter survival following cisplatin-based therapy. 2. Female gender seems to be significantly associated with longer survival in cisplatin-treated advanced stage NSCLC. 3. Leukocytosis shows mild statistical trend of association with shorter survival. 4. Consideration of these factors can be helpful during selection of suitable chemotherapy for management of these patients. A larger sample in this particular treatment category, possibly with a multi-institution cohort study using ERCC1, gender and leukocytosis is warranted.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 231, Tuesday Afternoon