Operable non-small cell lung cancer: correlation of volumetric helical dynamic contrast-enhanced CT parameters with immunohistochemical markers of tumor hypoxia.
OBJECTIVE
To assess the relationship between helical dynamic contrast material-enhanced (DCE) computed tomographic (CT) parameters and immunohistochemical markers of hypoxia in patients with operable non-small cell lung cancer (NSCLC).


METHODS
After institutional review board approval was obtained, 20 prospective patients who were suspected of having NSCLC underwent whole-tumor DCE CT with kinetic modeling (Patlak analysis) 24 hours before scheduled surgery. Flow-extraction product (in milliliters per 100 milliliters per minute) and blood volume (in milliliters per 100 milliliters) were derived. After surgery, matched whole-tumor sections were stained for exogenous and endogenous markers of hypoxia (pimonidazole infused intravenously 24 hours before surgery, immediately after DCE CT; glucose transporter protein). Correlation between DCE CT parameters and immunohistochemical markers was assessed by using the Spearman rank correlation. DCE CT parameters and immunohistochemical markers were also compared according to pathologic subtype, grade, stage, and nodal status by using the Mann-Whitney test. P values less than .05 indicated a statistically significant difference.


RESULTS
Fourteen patients with confirmed primary NSCLC underwent resection. There were negative correlations between blood volume and pimonidazole staining (r = -0.48, P = .004), and between flow-extraction product and glucose transporter protein expression (r = -0.50, P = .002). Flow-extraction product was significantly higher in adenocarcinomas than in squamous cell tumors (17.73 vs 11.46; P = .043). Glucose transporter protein expression was significantly lower for adenocarcinomas than for squamous tumors (14.07 vs 33.03; P < .001) and in node negative than in node positive tumors (15.63 vs 23.85; P = .005).


CONCLUSIONS
Blood volume and flow-extraction product derived at DCE CT correlated negatively with pimonidazole and glucose transporter protein expression, indicating the potential of these CT parameters as imaging biomarkers of hypoxia.
Mount Vernon Cancer Centre, Northwood, England.
Henry C
HC
Mandeville
Quan Sing
QS
Ng
Frances M
FM
Daley
Paul R
PR
Barber
Glenn
G
Pierce
Jessica
J
Finch
Margaret
M
Burke
Alex
A
Bell
Edward R
ER
Townsend
Robert
R
Kozarski
Boris
B
Vojnovic
Peter J
PJ
Hoskin
Vicky
V
Goh
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001810:Blood Volume; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery*; D003287:Contrast Media; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007472:Iohexol / Q000031:analogs & derivatives; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009593:Nitroimidazoles; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents; D011857:Radiographic Image Interpretation, Computer-Assisted; D018709:Statistics, Nonparametric; D036542:Tomography, Spiral Computed / Q000379:methods*
D014408:Biomarkers, Tumor; D003287:Contrast Media; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C093233:iobitridol; D007472:Iohexol; C033815:pimonidazole