Interrelationship of proliferation and hypoxia in carcinoma of the cervix

Purpose: In human cervix cancer treated with radiotherapy, we have previous ly shown from separate groups of patients that tumor hypoxia and proliferat ion rate as measured by bromodeoxyuridne (BrdU) labeling index (LI) are imp ortant determinants of clinical outcome. We now examine the relationship of these two pre-treatment predictive assays in 43 patients studied prospecti vely from 1994-98 where both tests were performed for each patient, Material and Methods: Newly diagnosed patients with carcinoma of the cervix were examined under anesthesia for staging purposes. Patients were given B rdU (200 mg) by intravenous route prior to the procedure. Tumor oxygenation was measured with the Eppendorf pO(2) histograph. Biopsy of tumor was then performed and the BrdU LI was obtained by how cytometry, The degree of tum or hypoxia for each tumor was expressed as median pO(2) values, and as the percentage of pO(2) readings <5 mmHg (HP5), Results: The median age was 53 years (range 23-79 years). There were 32 squ amous, and 11 non-squamous carcinomas. FIGO stages were: IB and IIA, 8; IIB , 17; IIIB, 18; with a median tumor size of 6 cm (range 2-10 cm), The patie nts received uniform treatment with radical radiation therapy. There were 2 2 diploid and 21 aneuploid tumors. The median LI, pO(2), and HP5 were 8.0%, 5.4 mmHg, and 46.8%, respectively, Tests for linear associations showed no significant correlation between median pO(2) vs, LI (r = 0.078, p = 0.62), and HP5 vs, LI (r = -0.14,p = 0.38), Conclusions: The clinical outcome in this group of patients is immature, bu t these results suggest that tumor hypoxia and proliferation measurements a re independent and potentially complementary predictive assays in cervix ca rcinoma. Further investigations are required to examine the distribution of proliferating tumor cells and its relationship with hypoxic tumor cells in tissue sections with the use of immunohistological techniques and image an alysis systems, (C) 2000 Elsevier Science Inc.