Pretreatment apoptosis in carcinoma of the cervix correlates with changes in tumour oxygenation during radiotherapy

Abstract

A relationship between hypoxia and apoptosis has been identified in vitro and in experimental tumours. The aim of this study was to investigate the relationship between apoptosis, hypoxia and the change in oxygenation during radiotherapy in human squamous cell carcinoma of the cervix. Forty-two patients with locally advanced disease underwent pretreatment evaluation of tumour oxygenation using an Eppendorf computerized microneedle electrode. Twenty-two of these patients also had a second evaluation of tumour oxygenation after receiving 40–45 Gy external beam radiotherapy. Paraffin-embedded histological sections were obtained from random pretreatment biopsies for all 42 patients. Apoptotic index (AI) was quantified by morphology on TUNEL stained sections. No correlation was found between pretreatment measures of AI and either the median pO2(r = 0.12, P = 0.44) or percentage of values < 5 mmHg (r = –0.02, P = 0.89). A significant positive correlation was found between AI and the change in tumour oxygenation (ratio of pre:post-treatment % values < 5 mmHg) following radiotherapy (r = 0.61, P = 0.002). The lack of correlation between apoptosis and hypoxia may occur because the Eppendorf measures both acute and chronic hypoxia, and the relative ability of acute hypoxia to induce apoptosis is unknown. These results indicate that cell death via apoptosis may be a mechanism of tumour reoxygenation during radiotherapy. © 2000 Cancer Research Campaign

How to overcome (and exploit) tumor hypoxia for targeted gene therapy

“…On the other hand, in patients with primary soft tissue sarcoma, no association was found between median pO 2 and p53 status (Nordsmark et al, 2001a). In squamous cell carcinoma of the cervix, the pre-radiotherapy apoptotic index did not correlate with pre-treatment oxygenation (both hypoxic fraction and median pO 2 ), but correlated significantly with the change in oxygenation post-treatment, ascribed by the authors to reduced interstitial fluid pressure as a result of cell loss via apoptosis (Sheridan et al, 2000).…”

In Vitro and In Vivo Antitumor Activity of Indolo[2,3-b] Quinolines, Natural Product Analogs from Neocryptolepine Alkaloid

“…H and E-stained slides of tumor specimens were used also used to calculate the H score [ 55 ] as well as the mitosis counting [ 56 ] and apoptotic tumor cell counting [ 57 , 58 ], ten arbitrarily chosen microscopic fields were used for each mitosis and apoptotic tumor cell counting, this was considered as examining at least 1000 tumor cells. High magnification (400×) was used for microscopic examination.…”

A role for dynamic contrast-enhanced magnetic resonance imaging in predicting tumour radiation response

“…This has led to extensive interest in developing biomarkers of hypoxia ( Tatum et al , 2006 ). Perhaps the most effective, to date, has been the Eppendorf Histograph, which was successfully used to stratify human tumours at various disease sites based on various oxygen-related criteria such as hypoxic fraction, median pO 2 or ratio of tumour to local normal tissue ( Falk et al , 1992 ; Fyles et al , 1998 ; Rofstad et al , 2000 ; Sheridan et al , 2000 ; Mo vs as et al , 2002 ; Le et al , 2006 ; Vaupel and Mayer, 2007 ). However, electrode application is highly invasive and is seldom used today.…”