C. W. E. Redman

Epithelial ovarian cancer: influence of polymorphism at the glutathione S-transferase GSTM1 and GSTT1 loci on p53 expression.

The importance of polymorphism in the glutathione S-transferase GSTM1, GSTT1 and, cytochrome P450, CYP2D6 loci in the pathogenesis of epithelial ovarian cancer has been assessed in two studies; firstly, a case-control study designed to determine the influence of these genes on susceptibility to this cancer, and secondly, the putative role of these genes in the protection of host cell DNA has been studied by comparing p53 expression in patients with different GSTM1, GSTT1 and CYP2D6 genotypes. The frequencies of GSTM1, GSTT1 and CYP2D6 genotypes in 84 cases and 325 controls were not different. Immunohistochemistry was used to detect p53 expression in 63 of these tumours. Expression was found in 23 tumours. Of the patients demonstrating immunopositivity, 20 (87%) were GSTM1 null. The frequency distributions of GSTM1 genotypes in p53-positive and -negative samples were significantly different (P = 0.002) and those for GSTT1 genotypes approached significance (exact P = 0.057). The proportion of patients with both GSTM1 null and GSTT1 null was also significantly greater in the immunopositive (4/22) than in the immunonegative group (1/40) (P = 0.0493). Single-strand conformational polymorphism (SSCP) analysis was used to detect mutations in the 23 tumour samples demonstrating p53 positivity. A shift in electrophoretic mobility of amplified fragments was found in 11 patients (exons 5, 6, 7 and 8) and these exons were sequenced. In eight samples a mutation was found. No SCCP variants were identified in the other 12 immunopositive patients. Sequencing of exons 4-9 of p53 from these tumours resulted in the detection of mutations in two patients (exons 5 and 7). Thus, in 23 patients who demonstrated immunopositivity, p53 mutations were found in nine patients with GSTM1 null (90.0%). In the 13 patients in whom no mutations were identified, 11 were GSTM1 null (84.6%). The data show that overexpression of p53 is associated with the GSTM1 null genotype. We propose the data are compatible with the view that GSTM1 and GSTT1 are critical in the detoxification of the products of oxidative stress produced during the repair of the ovarian epithelium. Thus, failure to detoxify products of this stress may result in damage to various genes in the host cell, including to p53, resulting in persistent expression of mutant protein. In other patients, oxidative stress effects damage to various genes, but not including p53, resulting in overexpression of wild-type p53.

Does histological incomplete excision of cervical intraepithelial neoplasia following large excision of transformation zone increase recurrence rates? A six year cytological follow up

Objective To determine the risk of recurrent cervical intraepithelial neoplasia (CIN) in women with complete or incomplete excision of cervical intraepithelial neoplasia treated by large loop excision of transformation zone (LLETZ).

Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells

SummaryThe expression of cyclin D1 protein in tumour sections from 81 patients with epithelial ovarian cancer was analysed using immunohistochemistry. The tumours that overexpressed cyclin D1 in more than 10% of neoplastic cells were considered positive. Thus overexpression of cyclin D1 was observed in 72/81 (89%) of the cases examined. Protein was detected in both the nucleus and the cytoplasm in 24/81 (30%) and localized exclusively in the cytoplasm in 48/81 (59%) of the tumours. Cyclin D1 was overexpressed in both borderline and invasive tumours. There was no association between protein overexpression and tumour stage and differentiation. Furthermore, no correlation between cyclin D1 expression and clinical outcome was observed. However, in tumours overexpressing cyclin D1 (n = 72), the proportion displaying exclusively cytoplasmic localization of protein was higher in those with serous compared with non-serous histology (P = 0.004, odds ratio 4.8, 95% confidence interval 1.4–19.1). Western analysis using a monoclonal antibody to cyclin D1 identified a 36 kDa protein in homogenates from seven tumours displaying cytoplasmic only and one tumour demonstrating both nuclear and cytoplasmic immunostaining. Using restriction fragment length polymorphism polymerase chain reaction and PCR-multiplex analysis, amplification of the cyclin D1 gene (CCNDI) was detected in 1/29 of the tumours demonstrating overexpression of cyclin D1 protein. We conclude that deregulation of CCND1 expression leading to both cytoplasmic and nuclear protein localization is a frequent event in ovarian cancer and occurs mainly in the absence of gene amplification.

Accuracy of colposcopy‐directed punch biopsies: a systematic review and meta‐analysis

Please cite this paper as: Underwood M, Arbyn M, Parry‐Smith W, De Bellis‐Ayres S, Todd R, Redman CWE, Moss EL. Accuracy of colposcopy‐directed punch biopsies: a systematic review and meta‐analysis. BJOG 2012;119:1293–1301.

The prognostic value of serum CA 125 in patients with advanced ovarian carcinoma: an analysis of 573 patients by the Medical Research Council Working Party on Gynaecological Cancer

A number of studies have suggested that serum CA 125 levels may be an important prognostic factor for survival of patients with ovarian carcinoma. We investigated, in a large group of patients from 11 UK centers, which combination of CA 125 measurements provided the best prognostic index, and whether the predictive power could be improved by the addition of other factors. Analysis of the data from 248 patients showed that the absolute value of the third CA 125 sample was the single most important factor for predicting progression at 12 months, with the addition of residual bulk only slightly improving the predictive power. Seventy-four patients had CA 125> 70, and of these 57% were correctly predicted to progress or die within 12 months, but 43% remained alive and progression free. The best predictor for progression produced a false positive rate of 19%. We therefore conclude that prognostic information based upon CA 125 measurements up to the start of the third course of initial chemotherapy is not accurate enough to be used to manage individual patients.

Do routine antibiotics after loop diathermy excision reduce morbidity

Objective To evaluate whether routinely giving an antibiotic after loop diathermy excision of the cervical transformation zone reduced post‐operative vaginal loss.

Cervical cytology/histology discrepancy: a 4-year review of patient outcome.

E. L. Moss, A. Moran, G. Douce, J. Parkes, R. W. Todd and C. E. W. Redman

Implementing the national invasive cervical cancer audit: a local perspective

Please cite this paper as: Moss E, Pearmain P, Askew S, Owen G, Reynolds T, Prabakar I, Douce G, Parkes J, Menon V, Todd R, Redman C. Implementing the national invasive cervical cancer audit: a local perspective. BJOG 2010;117:1411–1416.

A comparison of the side effects of prilocaine with felypressin and lignocaine with adrenaline in large loop excision of the transformation zone of the cervix: results of a randomised trial

Objective To test the hypothesis that prilocaine with felypressin causes fewer side effects than lignocaine with adrenaline when performing large loop excision of the transformation zone of the cervix.

The invasive cervical cancer review: psychological issues surrounding disclosure

An audit of the screening history of all new cervical cancer cases has been a requirement since April 2007. While NHS cervical screening programmes (NHSCSP) guidance requires that women diagnosed with cervical cancer are offered the findings of the audit, as yet there has been no research to investigate the psychological impact that meeting to discuss the findings might have on patients. This is in spite of the fact that cytological under‐call may play a role in as many as 20% of cervical cancer cases. This review draws on the literature concerning breaking bad news, discussing cancer and disclosing medical errors, in order to gain insight into both the negative and positive consequences that may accompany a cervical screening review meeting. We conclude that while patients are likely to experience some distress at disclosure, there are also likely to be positive aspects, such as greater trust and improved perception of care.