Abstract
ABSTRACTThe standard treatment for locally advanced cervical cancer (CC) is chemoradiotherapy. Once the bladder receives part of the radiation, a typical inflammatory condition that configures radiation-induced cystitis may develop. Chronic radiation-induced cystitis is commonly characterized by the bladder new submucosal vascularization, which is typically fragile and favors hematuria. The current study aims to investigate if Hypoxia-Induced Factor (HIF-1α) and its transcriptional target Vascular Endothelial Growth Factor A (VEGF-A) could be a primary pathway leading to increased submucosal vascularization. HIF-1α and VEGF-A mRNA levels in bladder core biopsies from CC patients treated with radiotherapy versus untreated (non-irradiated) patients were analyzed using a droplet digital polymerase chain reaction technology. Gene expression results showed that HIF-1α and VEGF-A had no significant differences between bladder samples from patients previously irradiated and untreated patient samples. However, a direct relationship between the degree of late morbidity and the expression of HIF-1α and VEGF-A has been demonstrated. Despite the lack of statistical significance precludes a definitive conclusion, the data presented herein suggests that further studies investigating the role of HIF-1α in bladder neovascularization in radiation-induced cystitis are highly recommended.
Highlights
Cervical cancer (CC) is the fourth most common malignancy diagnosed in women worldwide
In light of the important role of hypoxia in increase submucosal vascularization in the radiation-damaged bladder we evaluated the possible involvement of HIF-1α and its transcriptional target, Vascular Endothelial Growth Factor A (VEGF-A), in bladder tissue samples from CC patients undergoing radiotherapy versus untreated CC patients
We have found that patients with higher RTOG/EORTC toxicity score exhibited a trend toward higher HIF-1α mRNA levels, in a directly proportional way
Summary
Cervical cancer (CC) is the fourth most common malignancy diagnosed in women worldwide. In Brazil, CC is the third most common cancer and the third cause of cancer death in women [1]. The standard treatment for locally advanced CC is chemo-radiotherapy. Once the bladder receives part of the radiation, a typical inflammatory condition that configures radiation-induced cystitis (actinic cystitis) may develop. The reported incidence of late actinic cystitis that are related to pelvic neoplasms radiotherapy varies from 5 to 10% [2]. Radiation-induced cystitis has already been estimated to range between 8 and 12% in CC patients, with moderate or severe sequelae ranging between 2 and 6% [3]. Levenback et al reported an incidence of 6.5% in 1.784 stage IB
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