Estrogen receptor polymorphisms and the risk of endometrial cancer.

OBJECTIVE: There is evidence that estrogens and some of their metabolites are involved in endometrial cancer pathogenesis. As estrogens mediate their effects via the estrogen receptors, ESR1 and ESR2, the objective of this investigation was to determine whether six single nucleotide polymorphisms (SNPs) in these two genes were over-represented in a population of endometrial cancer patients compared with a healthy matched control population, thereby associating differences in these genes with endometrial cancer. DESIGN: The study is a case-control investigation large enough to detect a two-fold increased risk, assuming a dominant genetic model, with P = 0.05 and 80% power. SETTING: The study and control populations were all from the Hunter-New England region of New South Wales, Australia collected between the years 1992 and 2005. POPULATION: The study consisted of 191 endometrial cancer patients and 291 healthy controls matched for gender and age. METHODS: Two SNPs in ESR1 and four SNPs in ESR2 were genotyped using PCR-based restriction fragment length polymorphism analysis and real-time PCR. Odds ratios were calculated using unconditional logistic regression and SIMHAP was used for haplotype analysis, adjusting for potential endometrial cancer risk factors. Kaplan-Meier survival analysis, Cox regression and t tests were used to examine the patient's age of diagnosis of endometrial cancer and genotype. MAIN OUTCOME MEASURES: Over-representation of ESR1 and ESR2 polymorphisms in the endometrial cancer population compared with the control population indicates an involvement in the development and/or progression of disease. RESULTS: Two ESR1 (rs2234693 and rs9340799) and two ESR2 (rs1255998 and rs944050) polymorphisms were associated with an increased risk of endometrial cancer. Following adjustment for risk factors, the association with the ESR1 and ESR2 polymorphisms (rs2234693, rs1255998 and rs944050) remained highly significant. Haplotype analysis revealed that carriers of the ESR1 haplotype (variant alleles; rs2234693 and rs9340799) and the ESR2 haplotype (variant allele; rs1255998 and wild-type alleles; rs944050, rs4986938 and rs1256049) were at an increased risk (OR 1.862, P = 0.013 and OR 1.918, P = 0.046 respectively). This risk was even greater in women carrying both risk haplotypes (OR 5.041, P = 0.007). CONCLUSIONS: Our data suggest that the ESR1 (rs2234693 and rs9340799) and the ESR2 (rs1255998 and rs944050) polymorphisms may be associated with an increased risk of developing endometrial cancer.

Clinicopathologic review of malignant polyps in stage 1A carcinoma of the endometrium.

OBJECTIVES: The aims of this study were to determine the incidence of malignant polyps in stage 1A endometrial cancer, to define the pathological features of such cancers, and to assess whether clinical outcome differs from similar cancers without a malignant polyp. METHODS: We performed a retrospective pathological review of 107 cases of stage 1A endometrial cancer treated at two centers in New South Wales between January 1988 and July 2003. The presence of a malignant polyp was determined and a pathological description made of the tumor. Clinical data were collected, including prior tamoxifen usage, tumor recurrence and survival. The outcome of the malignant polyp group was compared to the same histological subtype not involving a malignant polyp. RESULTS: The incidence of malignant polyps in our series was 32%. Malignant polyps occurred in all 8 cases involving a serous subtype. Precursor lesions of endometrial cancer were identified within malignant polyps. Three out of the four recurrences occurred in high-grade tumor subtypes and all four had a large primary tumor (size > or = 4 cm). When comparing the same subtype of tumor with and without a malignant polyp, there was no significant difference in clinical outcome. CONCLUSIONS: Approximately one-third of stage 1A endometrial cancers are associated with a malignant polyp. Serous carcinoma commonly arises within an otherwise benign endometrial polyp. Malignant polyps offer an opportunity to identify precursors of endometrial carcinoma. Clinical outcome of stage 1A endometrial carcinoma was related to the histological subtype and the size of the tumor rather than the presence of a malignant polyp.

Early-stage vaginal carcinoma--an analysis of 70 patients.

OBJECTIVES: The aims of this study were to assess outcomes and define prognostic factors for early-stage vaginal carcinoma. METHODS: A retrospective analysis was performed of women with FIGO stages I and II vaginal carcinoma identified from the database of the Queensland Centre for Gynaecological Cancer between January 1982 and December 1998. RESULTS: Seventy women were identified. The 5-year survivals for stages I and II carcinomas were 71 and 48%, respectively (P < 0.05). Sixty-one patients (87%) had squamous cell carcinomas with a 5-year survival of 68% versus 22% for adenocarcinomas (P < 0.01). Those women with grade 3 tumors had a 5-year survival of 40% versus 69% for grades 1 and 2 (P < 0.05). Tumor size and site were not significant prognostic factors. Patients treated by surgery alone or with combined surgery and radiotherapy had a significantly improved survival compared to the radiation alone group (P < 0.01). Eighty-five percent of recurrences were locoregional. The median time to relapse was 12 months after initiation of therapy. CONCLUSION: Tumor morphology, grade, and stage are important prognostic indicators. Measures aimed at improving local control of the disease, including surgery, are necessary.

A case of early-stage epithelial ovarian cancer in pregnancy.

There are few reports in the literature of platinum-based chemotherapy administered in pregnancy. We present a case of serous adenocarcinoma of the ovary complicating pregnancy. Following laparotomy at 16 weeks of gestation, four cycles of cisplatin were administered prior to confinement at 32 weeks. There were no neonatal sequelae. We believe there is increasing evidence for the safe use of cisplatin in pregnancy.

Transfusion rate associated with hysterectomy for benign disease.

The transfusion rate associated with hysterectomy for benign disease is an indirect indicator of haemorrhage. It is used in quality assurance activities and is one measure of standard of care. This retrospective study was conducted to determine the transfusion rate for these operations in a tertiary referral hospital. In addition, it was considered that the information could be used in deciding the need for a routine preoperative group and save policy (G and S). The Blood Bank records of all women undergoing hysterectomy for benign disease from 1993-1998 were examined and the number of women transfused was recorded. A total of 1220 hysterectomies were performed. Of women having vaginal hysterectomies only 0.38% required transfusion compared with 2.18% for abdominal hysterectomies. These data suggest that there is no need for a strict policy of preoperative G and S for all patients. In addition, this information can be used as a benchmark when reviewing morbidity associated with hysterectomy and in particular when various methods of hysterectomy are compared.