Aromatase expression predicts survival in women with early-stage non small cell lung cancer.
Estrogen signaling is critical in the progression of tumors that bear estrogen receptors. In most patients with breast cancer, inhibitors that block interactions of estrogen with its receptors or suppress the production of endogenous estrogens are important interventions in the clinic. Recent evidence now suggests that estrogen also contributes to the pathogenesis of non-small cell lung cancer (NSCLC). We used a human lung cancer xenograph model system to analyze the effect of aromatase or estradiol on tumor growth. We further examined the level of protein expression of aromatase in 422 patients with NSCLC using a high-density tissue microarray. Results were confirmed and validated on an independent patient cohort (n = 337). Lower levels of aromatase predicted a greater chance of survival in women 65 years and older. Within this population, the prognostic value of aromatase was greatest in earlier stage lung cancer (stage I/II). In addition, for women with no history of smoking, lower aromatase levels were a strong predictor of survival. Our findings implicate aromatase as an early-stage predictor of survival in some women with NSCLC. We predict that women whose lung cancers have higher levels of aromatase might be good candidates for targeted treatment with aromatase inhibitors.
Mah
Vei
V
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1747, USA.
Seligson
David B
DB
Li
Ai
A
Márquez
Diana C
DC
Wistuba
Ignacio I
II
Elshimali
Yahya
Y
Fishbein
Michael C
MC
Chia
David
D
Pietras
Richard J
RJ
Goodglick
Lee
L
D000328:Adult; D000368:Aged; D000818:Animals; D001141:Aromatase / Q000032:analysis*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D012907:Smoking
D047072:Aromatase Inhibitors; D001141:Aromatase