Peritoneal endometriotic lesions were innervated by sensory Adelta, sensory C, cholinergic and adrenergic nerve fibres. These nerve fibres may play an important role in the mechanisms of pain generation in this condition.

Of the few factors known to be associated with epithelial ovarian cancer, the most consistently observed relate to women's reproductive function, although even here uncertainties remain. We have undertaken a case-control study involving personal interviews with over 1,600 women, the largest of its kind to date, to investigate further the associations between women's reproductive histories and other factors and the development of ovarian cancer. Cases were drawn from women diagnosed with epithelial ovarian cancer in 3 Australian states, Queensland, New South Wales and Victoria, between August 1990 and December 1993, and controls were drawn at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed information about women's reproductive and contraceptive histories and other factors of interest, such as smoking and family history of ovarian or other cancer. Findings were based on data from 824 cases and 860 controls and confirmed the reduced risk of ovarian cancer associated with increasing parity and duration of use of the oral contraceptive pill (OCP), hysterectomy and tubal ligation. The strongest association of all was seen with use of the OCP for 10 years or more. An inverse association between ovarian cancer and age at first birth was observed, but this was not statistically significant. There were no associations between development of ovarian cancer and number of incomplete pregnancies, use of hormone replacement therapy or menstrual history. Among other factors considered, education after leaving school was negatively associated and high body mass index, family history of ovarian cancer, use of talc in the abdominal or perineal region and smoking were positively associated with occurrence of ovarian cancer.

Small nerve fibres detected in the functional layer in all women with endometriosis may have important implications for understanding the generation of pain in these patients. The presence of nerve fibres in an endometrial biopsy may be a novel surrogate marker of clinical endometriosis.

Neurogenesis in the ventricular layer and the development of cell topography in the ganglion cell layer have been studied in whole-mounts of human fetal retinae. At the end of the embryonic period mitotic figures were seen over the entire outer surface of the retina. By about 14 weeks gestation mitosis had ceased in central retina and differentiation of photoreceptor nuclei was evident within a well-defined area which constituted about 2% of total retina area. This area was approximately centered on the site of the putative fovea, identified by the exclusive development of cone nuclei at that location. The area of retina in which mitosis had ceased increased as gestation progressed. By mid-gestation mitosis in the ventricular layer occupied about 77% of the outer surface of the retina and by about 30 weeks gestation mitosis in the ventricular layer had ceased. Cell density distributions in the ganglion cell layer were nonuniform at all stages studied (14-40 weeks). Densities were highest at about 17 weeks gestation, and by mid-gestation the adult pattern of cell topography was present with maps showing elevated cell densities in posterior retina and along the horizontal meridian. Cell densities generally declined throughout the remainder of the gestation period, except in the posterior retina, where densities in the perifoveal ganglion cell layer remained high during the second half of gestation. There is a rapid decline in cell density in the foveal ganglion cell layer toward the end of gestation, and it is suggested that the persistence of high densities in the perifoveal region may be related to migration of cells away from the developing fovea. The total population of cells in the ganglion cell layer was highest (2.2-2.5 million cells) between about weeks 18 and 30 of gestation. After this the cell population declined rapidly to 1.5-1.7 million cells. It is suggested that naturally occurring neuronal death is largely responsible for this decline.

Purpose: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinumbased chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies.Experimental Design: We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling.Results: We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC.Conclusion: Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents. Clin Cancer Res; 20(24); 6618-30. Ó2014 AACR.

We propose that in eutopic endometrium in women with endometriosis Foxp3+ cells decrease the ability of newly recruited immune cell populations to effectively recognize and target endometrial antigens shed during menstruation, allowing their survival and ability to implant in ectopic sites. At these ectopic sites, variable expression of Foxp3+ cells within some peritoneal endometriotic lesions is likely to be linked to the characteristics and stage of individual lesion development and be playing key roles in pathogenesis and progression of this unique condition.

This study further supports an association between immune changes in eutopic endometrium and presence of endometriosis. However, it remains uncertain if eutopic immune changes are primary or secondary occurrences.

Proton MR spectroscopy of fine-needle biopsy specimens provides objective diagnostic information that complements findings of conventional preoperative investigations of breast lesions.