Phosphorylated AKT (pAKT) is a major contributor to radioresistance in human cancers. The aim of this study was to investigate the association of pAKT expression and radiation resistance in cervical cancer. A retrospective review was made of the records of 27 women who received primary radiation therapy due to locally advanced cervical cancer (LACC) with FIGO stage IIB–IVA. Nine patients regarded as radiation resistant developed local recurrences with a median progression free interval of 9 months. Eighteen patients did not show local recurrences, and were regarded as a radiation-sensitive group. Using pretreatment paraffin-embedded tissues, we evaluated pAKT expression by immunohistochemistry. A significant association was found between the level of pAKT expression and local recurrence. Immunohistochemical staining for pAKT was significantly more frequent in the radiation-resistant than in the radiation-sensitive group (P=0.004). The mean progression-free survival was 86 months for patients with pAKT-negative staining (19 cases) and 44 months for patients with pAKT-positive expression (eight cases) (P=0.008). These results suggest that signalling from phosphatidylinositide 3-kinase/pAKT can lead to radiation resistance, and that evaluation of pAKT may be a prognostic marker for response to radiotherapy in LACC.

Kim MK, et al. J Gynecol Oncol. 2010 Sep;21(3):181-185. http://dx.doi.org/10.3802/jgo.2010.21.3.181

The annexins (ANXs) have diverse roles in tumor development and progression, however, their clinical significance in cervical cancer has not been elucidated. The present study was to investigate the clinical significance of annexin A2 (ANXA2) and annexin A4 (ANXA4) expression in cervical cancer. ANXA2 and ANXA4 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 46 normal cervical epithelium samples and 336 cervical cancer cases and compared the data with clinicopathological variables, including the survival of cervical cancer patients. ANXA2 expression was lower in cancer tissue (p = 0.002), whereas ANXA4 staining increased significantly in cancer tissues (p < 0.001). ANXA2 expression was more prominent in squamous cell carcinoma (p < 0.001), whereas ANXA4 was more highly expressed in adeno/adenosquamous carcinoma (p < 0.001). ANXA2 overexpression was positively correlated with advanced cancer phenotypes, whereas ANXA4 expression was associated with resistance to radiation with or without chemotherapy (p = 0.029). Notably, high ANXA2 and ANXA4 expression was significantly associated with shorter disease-free survival (p = 0.004 and p = 0.033, respectively). Multivariate analysis indicated that ANXA2+ (HR = 2.72, p = 0.003) and ANXA2+/ANXA4+ (HR = 2.69, p = 0.039) are independent prognostic factors of disease-free survival in cervical cancer. Furthermore, a random survival forest model using combined ANXA2, ANXA4, and clinical variables resulted in improved predictive power (mean C-index, 0.76) compared to that of clinical-variable-only models (mean C-index, 0.70) (p = 0.006). These findings indicate that detecting ANXA2 and ANXA4 expression may aid the evaluation of cervical carcinoma prognosis.

The aim of the present study was to evaluate the efficacy of misoprostol administered orally, vaginally, or sublingually on cervical ripening before hysteroscopic surgery in premenopausal non-pregnant women. Non-pregnant premenopausal women scheduled for operative hysteroscopy (with a 10-mm hysteroscope) were assigned by computerized randomization to receive 400 mg of misoprostol, administered either orally or vaginally 6–8 h prior to surgery or 400 mg sublingually 2–4 h prior to surgery. The primary outcome in this study was the preoperative cervical width as measured by the largest number of Hegar dilators. The time to Hegar number 10 was also recorded along with side effects related to misoprostol and complications during surgery for each group. Patients were randomized to receive sublingual (n = 47), oral (n = 47) or vaginal (n = 47) misoprostol. The three groups were comparable in terms of age, BMI (body mass index), parity, gravidity, history of vaginal delivery, post-operative pathological findings and surgeon type. The preoperative cervical width [sublingual: 7.5 ± 2.0 mm (8, 3–10); oral: 7.5 ± 1.9 mm (7, 4–10); vaginal: 7.6 ± 2.4 mm (8, 1–10)] was statistically similar among the groups. The time to Hegar number 10, side effects and complications during the hysteroscopy were comparable among the three groups. A limitation of this study was that the surgeons, but not the patients, were blinded to the test procedures. Nevertheless we found that sublingual, oral and vaginal misoprostol were equally effective for cervical priming before hysteroscopic surgery in premenopausal non-pregnant women. The trial was registered under ClinicalTrials.gov identifier NCT01024270.