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Standard molecular classification of endometrial cancers (EC) is now endorsed by the WHO and identifies p53-abnormal (p53abn) EC as the subgroup with the poorest prognosis and the most likely to benefit from adjuvant chemo(radio)therapy. P53abn EC are POLE wildtype, mismatch repair proficient and show abnormal immunohistochemical (IHC) staining for p53. Correct interpretation of routinely performed p53 IHC has therefore become of paramount importance. We aimed to comprehensively investigate abnormal p53 IHC patterns and their relation to clinicopathological and molecular features. Tumor material of 411 molecularly classified high-risk EC from consenting patients from the PORTEC-3 clinical trial were collected. p53 IHC was successful in 408 EC and was considered abnormal when the tumor showed a mutant expression pattern (including subclonal): overexpression, null or cytoplasmic. The presence of pathogenic mutations was determined by next generation sequencing (NGS). Abnormal p53 expression was observed in 131/408 (32%) tumors. The most common abnormal p53 IHC pattern was overexpression (n = 89, 68%), followed by null (n = 12, 9%) and cytoplasmic (n = 3, 2%). Subclonal abnormal p53 staining was observed in 27 cases (21%), which was frequently but not exclusively, associated with POLE mutations and/or MMRd (n = 22/27; p < 0.001). Agreement between p53 IHC and TP53 NGS was observed in 90.7%, resulting in a sensitivity and specificity of 83.6% and 94.3%, respectively. Excluding POLEmut and MMRd EC, as per the WHO-endorsed algorithm, increased the accuracy to 94.5% with sensitivity and specificity of 95.0% and 94.1%, respectively. Our data shows that awareness of the abnormal p53 IHC patterns are prerequisites for correct EC molecular classification. Subclonal abnormal p53 expression is a strong indicator for POLEmut and/or MMRd EC. No significant differences in clinical outcomes were observed among the abnormal p53 IHC patterns. Our data support use of the WHO-endorsed algorithm and combining the different abnormal p53 IHC patterns into one diagnostic entity (p53abn EC).

Incidence trends for vulval cancer between 1974 and 1994 within a geographically static population are reported. The age standardized incidence rate for combined vulval tumor types is increasing (P=0.014). A similar trend for squamous cell carcinoma of the vulva was observed which may be important, but this did not reach statistical significance. A subgroup analysis of age at diagnosis, tumor stage, smoking history and parity for the two time periods 1974-83 and 1984-94 failed to identify changes which might identify an underlying cause for this rise. Careful scrutiny of pathology records detected significant cancer registry underascertainment. Further population based studies in other geographic areas would be useful to confirm this rise and to examine further trends in squamous cell carcinoma incidence.

Menstrual disorders are common, accounting for about 3% of female consultations in general practice. Although only 10% are referred to a specialist, GP referrals for dysfunctional uterine bleeding (DUB) went up by 73% between 1971 and 1981 in England and Wales. ~ First line management is usually medical, using prostaglandin synthetase inhibitors, progestagens, danazol, antifibrinolytics, ethamsylate or even LHRH analogues. However, medical treatment is frequently ineffective, may cause unacceptable sideeffects, and any therapeutic effect may be temporary. This has led to an increasing demand in the last 30 years for hysterectomy, which has until recently been the only definitive treatment. The current lifetime risk of a woman undergoing hysterectomy is 20% in the UK,-40% in Australia, and around 50% in the USA. The hysterectomy rate in Scotland has doubled since 1960 due almost exclusively to an increase in operations for menstrual disorders, mainly in women aged 35-44. 2 In Scotland in 1984, 35% of hysterectomies were for menstrual disorders; similarly 30% of hysterectomies in the Oxford region in 1988 were for disorders of menstruation) This desire by an increasing number of women for effectivetreatment of DUB has led to a need for less invasive surgical treatment than hysterectomy. This has stimulated the introduction of hysteroscopically guided destruction of the endometrium. An impression may be given by enthusiasts of so-called 'minimally invasive' surgery that hysterectomy for

The objective of this study was to compare the frequency of two common p21WAF1/Cip1 gene polymorphisms in ovarian cancer patients with that in age-matched controls, from a population originating from Eastern Scotland. Both polymorphisms were found significantly less frequently in both the constitutive and tumour tissue DNA of ovarian cancer patients (3/65; 4.6%), than in that from geographically and age-matched controls (25/186; 13.4%) (p=0.0495, chi2). Furthermore, we found no p21WAF1/Cip1 gene mutations in any of the tumours, reflected by a relatively low degree of loss of heterozygosity (LOH) at the chromosomal region where the gene maps, providing further evidence that the p21WAF1/Cip1 gene is not mutated in ovarian cancer. The data suggest however, that there may potentially be a protective function for the two p21WAF1/Cip1 gene polymorphisms in the population under study.

A cluster of five patients with endometrial carcinosarcoma (malignant mixed Müllerian tumor) occurred at our center during 1993; four of these had been prescribed long-term tamoxifen for breast carcinoma. Searching the archives for the 9-year period 1983–1992 revealed two further cases of uterine carcinosarcoma occurring in patients prescribed tamoxifen, from a total of 16 cases of this tumor. Five of the six patients diagnosed with carcinosarcoma who had been taking tamoxifen had been maintained on the drug for at least 6 years, while the other had a 3-year history of tamoxifen therapy. From these data we raise the question of an association between long-term tamoxifen treatment and development of endometrial carcinosarcoma, following the dramatic increase in the prescribing of this drug after 1984.

Both cervical cancer and its precancerous state cervical intraepithelial neoplasia (CIN) have the characteristics of being sexually transmitted. Formerly herpes simplex virus (HSV) but more recently human papillomavirus (HPV) which both infect the cervix have been implicated in causation. The role of these viruses as possible initiators of cancer or as potential cofactors or cocarcinogens is discussed at the molecular level within the context of the disease process.

DNA extracted from eight human cervical carcinomas, one lymph node metastasis and related control tissue was examined for the presence of herpes simplex virus (HSV) DNA sequences. Southern blot transfers of tumour and control DNA were hybridised with radioactively labelled cloned probes representing 70% of the HSV-2 genome. Specific hybridisation to HSV DNA sequences was observed in one of eight carcinoma tissues analysed. Hybridisation of HSV-2 DNA probes to BamHI and XhoI restriction enzyme fragments of tumour cell DNA which co-migrated with authentic HSV-2 viral fragments identified co-linear HSV-2 DNA sequences comprising 3% of the HSV-2 genome, between map coordinates 0.582 and 0.612. The remaining eight tumour and all control tissues analysed, showed no specific hybridisation to any of the probes used at levels of sensitivity which would detect 0.5 copies/cell of HSV-2 DNA restriction fragments of 2 kb or greater.

Parkerising is the treatment of iron and steel by immersion in an aqueous solution to form a heavy phosphate coating. In this case heavy means to Def. Class 1 or 2 Process or as defined by BS.3189 Class A1 or A2, and includes iron, zinc and manganese phosphate processes, such as Parker F, Parker 30 and Parker 85. The treatment is a two‐stage process, the first being the actual phosphate treatment and the second the sealing coat. The processes are so designed as to give an absorbent surface which is capable of retaining the subsequent finish to enhance the corrosion resistance.