Comparison of molecular markers of hypoxia and imaging with (60)Cu-ATSM in cancer of the uterine cervix.

PURPOSE

To determine if hypoxia-related molecular markers are associated with (60)Cu labeled diacetyl-bis (N4 -methylthiosemicarbazone); ((60)Cu-ATSM) imaging of tumor hypoxia in cervical cancer.

PROCEDURES

Fifteen patients were enrolled in a prospective study and underwent evaluation of tumor hypoxia with positron emission tomography (PET) using (60)Cu-ATSM. (60)Cu-ATSM-PET imaging was compared with the expression of tissue molecular markers, which included vascular endothelial growth factor (VEGF), cyclo-oxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), carbonic anyhdrase IX (CA-9), and apoptotic index.

RESULTS

Six patients had hypoxic tumors determined by (60)Cu-ATSM, and nine had non-hypoxic tumors. The 4-year overall survival estimates were 75% for patients with non-hypoxic tumors and 33% for those with hypoxic tumors (p = 0.04). Overexpression of VEGF (p = 0.13), EGFR (p = 0.05), CA-9 (p = 0.02), COX-2 (p = 0.08), and the presence of apoptosis (p = 0.005) occurred in patients with hypoxic tumors. Cox proportional hazards modeling demonstrated hypoxia as determined by (60)Cu-ATSM to be a significant independent predictor of tumor recurrence (p = 0.0287).

CONCLUSIONS

(60)Cu-ATSM hypoxia was correlated with overexpression of VEGF, EGFR, COX-2, CA-9, an increase in apoptosis, and a poor outcome.