Correlation between matrix metalloproteinase 9 and 18F-2-fluoro-2-deoxyglucose-positron emission tomography as diagnostic markers of lung cancer.
OBJECTIVE
This study was conducted to evaluate the diagnostic role of matrix metalloproteinase 9 (MMP9) measured in bronchoalveolar lavage (BAL), serum and tissue samples of patients with indeterminate lung lesions and its correlation with F-18-2-fluoro-2-deoxyglucose-positron emission tomography ((18)FDG-PET) findings in diagnostic work.


METHODS
MMP9 levels (ng/ml) in serum and BAL were analysed using enzyme-linked immunosorbent assay in 60 consecutive patients with lung mass. (18)FDG-PET was performed on all patients and a standard uptake value (SUV) threshold of 2.5 was used to differentiate benign from malignant lesions. In tissue samples of resectable patients, MMP9 expression was also revealed by immunohistochemical staining.


RESULTS
Twenty patients had benign disease and 40 patients had malignant lesions, of which 7 (17.5%) were classified as Stage I, 18 (45%) as Stage II, 7 (17.5%) as Stage III and 8 (20%) as Stage IV. MMP9 levels in serum were significantly higher in malignant than in benign lesions (673 ± 182 versus 309 ± 96, respectively, P < 0.0001), and were significantly higher in patients with metastatic disease than in patients of other stage groups; no significant difference was found between different histological types. MMP9 levels in BAL were higher in malignant than in benign lesions (502 ± 137 versus 325 ± 118, respectively, P = 0.001); no significant differences were found between different stages or histological groups. In patients with malignant lesions, MMP9 levels in BAL were inversely correlated with FEV(1) (volume that has been exhaled at the end of the first second of forced expiration) and FVC (forced vital capacity of maximally forced expiratory effort) values. In patients with SUV > 2.5, MMP9 levels in serum and BAL had a sensitivity, specificity, positive predictive value and negative predictive value of 73, 100, 100 and 81% (cut-off point of 601; area under the curve (AUC): 0.7) and 94, 100, 100 and 83% (cut-off point of 745; AUC: 0.9), respectively. In patients with SUV < 2.5, MMP9 levels in serum and BAL had a sensitivity, specificity, positive predictive value and negative predictive value of 94, 100, 100 and 75% (cut-off point of 240; AUC: 0.9) and 70, 100, 100 and 73% (cut-off point of 321; AUC: 0.7), respectively. Of the 26 tumour samples, 9 (34%) showed positive immunohistochemical staining for MMP9.


CONCLUSIONS
The measurement of MMP9 levels helps to differentiate benign from malignant lung mass. Its use in combination with PET study adds further information to the diagnosis work-up of lesions to select patients who may or may not benefit from additional invasive procedures.
Thoracic Surgery Unit,  Second University of Naples, Naples,  Italy.
Alfonso
A
Fiorelli
Antonietta
A
Rizzo
Gaetana
G
Messina
Anna
A
Izzo
Giovanni
G
Vicidomini
Giuseppe
G
Pannone
Mario
M
Santini
Marina
M
Di Domenico
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D019788:Fluorodeoxyglucose F18; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals; D014797:Vital Capacity / Q000502:physiology
D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D020780:Matrix Metalloproteinase 9