Profiling the expression of cytochrome P450 in breast cancer.
OBJECTIVE
The cytochrome P450s (P450) are key oxidative enzymes that metabolize many carcinogens and anticancer drugs. Thus, these enzymes influence tumour development, tumour response to therapy and are putative tumour biomarkers. The aim was to define the P450 expression profile in breast cancer and establish the significance of P450 expression in this tumour type.


RESULTS
A tissue microarray containing 170 breast cancers of no special type was immunostained for a panel of 21 P450s. The highest percentage of strong immunopositivity in breast cancers was seen for CYP4X1 (50.8%), CYP2S1 (37.5%) and CYP2U1 (32.2%), while CYP2J (98.6%) and CYP3A43 (70.7%) were the P450s that most frequently displayed no immunoreactivity. CYP4V2 (P = 0.01), CYP4X1 (P = 0.01) and CYP4Z1 (P = 0.01) showed correlations with tumour grade. CYP1B1 (P = 0.001), CYP3A5 (P = 0.001) and CYP51 (P = 0.005) showed the most significant correlations with oestrogen receptor status. Correlations with survival were identified for CYP2S1 (P = 0.03), CYP3A4 (P = 0.025), CYP4V2 (P = 0.026) and CYP26A1 (P = 0.03), although none of these P450s was an independent marker of prognosis.


CONCLUSIONS
This study has defined the expression profile of cytochrome P450s in breast cancer and may offer their potential application as biomarkers to aid decisions regarding optimal adjuvant hormonal therapy.
Murray
Graeme I
GI
Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK. g.i.murray@abdn.ac.uk
Patimalla
Siva
S
Stewart
Keith N
KN
Miller
Iain D
ID
Heys
Steven D
SD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072470:Cytochrome P450 Family 4; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D040081:Protein Array Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase
D014408:Biomarkers, Tumor; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; D018719:Erb-b2 Receptor Tyrosine Kinases; D000072516:Retinoic Acid 4-Hydroxylase; C422564:CYP2S1 protein, human; C505357:CYP4V2 protein, human; C510163:CYP3A4 protein, human; C508053:ERBB2 protein, human