Genital chronic graft-versus-host disease in females: a cross-sectional study.

Using the National Institutes of Health (NIH) consensus criteria for chronic graft-versus-host disease (cGVHD), we assessed the prevalence, symptoms, and clinical signs of female genital cGVHD in a cross-sectional population-based study. Forty-two women were evaluated at a median of 80 months (range, 13 to 148 months) after undergoing hematopoietic stem cell transplantation (HSCT). Medical history, ongoing medications, and genital signs and symptoms were recorded. Gynecologic examination for the diagnosis and clinical scoring of genital cGVHD was combined with clinical scoring of extragenital cGVHD for the estimation of each patient's global cGVHD score. Biopsy specimens from the genital mucosa were obtained from 38 patients. Genital cGVHD was diagnosed in 22 of 42 patients (52%). Its presence was associated with systemic corticoid steroid treatment of extragenital cGVHD (P = .001), older age (P = .07), and HSCT from a sibling donor (P = .002). Five patients had isolated genital cGVHD. Dryness, pain, smarting pain (P < .05 for all), and dyspareunia (P = .001) were observed more frequently in the women with genital cGVHD. Twelve patients had advanced genital cGVHD (clinical score 3), which was the main factor explaining the high rate (15 of 42) of severe global cGVHD. The rate of genital cGVHD was similar (P = .37) in patients with a follow-up of ≥80 months (10 of 22) and those with a follow-up of <80 months (12 of 20). We found no convincing relationship between clinical diagnosis and histopathological assessment of mucosal biopsy specimens. In our group of women with a long follow-up after HSCT, genital cGVHD was common and in many cases incorrectly diagnosed. Genital cGVHD causes genital symptoms and affects sexual life, and may present without any other cGVHD, warranting early and continuous gynecologic surveillance in all women after HSCT.

Ovarian carcinoma histotype determination is highly reproducible, and is improved through the use of immunohistochemistry.

AIMS: To assess the variation in ovarian carcinoma type diagnosis among gynaecological pathologists from Nordic countries, and whether a rationally designed panel of immunohistochemical markers could improve diagnostic reproducibility. METHODS AND RESULTS: Eight pathologists from four countries (Sweden, Denmark, Norway, and Finland) received an educational lecture on the diagnosis of ovarian carcinoma type. All tumour-containing slides from 54 ovarian carcinoma cases were independently reviewed by the participants, who: (i) determined type purely on the basis of histology; (ii) indicated whether they would apply immunohistochemistry in their routine practice; and (iii) determined type after reviewing the staining results. The results for six markers (WT1, p53, p16, HNF-1ß, ARID1A, and progesterone receptor) were determined for all 54 cases, by staining of a tissue microarray. The median concordance with central review diagnosis was 86%, and significantly improved to 90% with the incorporation of immunostaining results (P = 0.0002). The median interobserver agreement was 78%, and significantly improved to 85% with the incorporation of immunostaining results (P = 0.0002). CONCLUSIONS: Use of the immunostaining results significantly improved both diagnostic accuracy and interobserver agreement. These results indicate that ovarian carcinoma type can be reliably diagnosed by pathologists from different countries, and also demonstrate that immunohistochemistry has an important role in improving diagnostic accuracy and agreement between pathologists.

Usefulness of current risk groups in the treatment of surgically staged endometrial carcinomas; a population-based study from Western Sweden.

BACKGROUND: Endometrial carcinoma is the most common malignancy of the female genital tract and its incidence is increasing. However, treatment results have not improved during the last decades. PATIENTS AND METHODS: Our regional quality register was used to evaluate treatment results for the period between January 1995 and December 2003. This study includes 2211 consecutive patients, of which 1993 surgically staged patients were evaluated in detail. Of these, 831 (53%) were at low risk and were given no further treatment after primary surgery. Patients with moderate- and high-risk tumors were postoperatively treated according to the respective protocols of one Swedish and one international study. Postoperative vaginal brachytherapy +/- external radiation was given to 486 (31%) patients at moderate risk, while 234 (15%) had high-risk disease and were randomized to external radiation + brachytherapy or external radiation + brachyterapy + chemotherapy. RESULTS: Overall cause-specific 5- and 10-year survival was 83.9% and 81.3%, respectively, for all included patients. The corresponding figures for surgically staged patients were 87.4% and 84.9%, respectively. One important observation was that there was no significant difference in survival between patients at low and moderate risk. CONCLUSION: The results strongly suggest that the risk groups used during this study period were not optimal. It is recommended to use smaller, better specified groups defined by more prognostic factors for enhanced individualization of treatment.

A population-based 5-year cohort study including all cases of epithelial ovarian cancer in western Sweden: 10-year survival and prognostic factors.

Epithelial ovarian cancer (EOC) is the major gynecologic cancer mortality cause in Sweden. The aim of the present study was to investigate the long-term survival and prognostic factors of a complete population-based 5-year cohort of 682 patients with invasive EOC in western Sweden (population around 1.6 million). Data relating to residual tumor after surgery, FIGO stage, grade, histopathologic subtype, ploidy status, adjuvant chemotherapy (the prepaclitaxel period), and disease state (recurrence and death) were reported to a quality register in a prospectively kept database and were controlled against the Swedish National Cancer Registry for completeness. The median follow-up durations for the prospectively collected data in the Cox analysis and for the survival analysis that was made for all patients were 81 months (range, 52-109 months) and 11.7 years (range, 8.7-14.1 years), respectively. No patient was lost to follow-up. The relative 10-year survival rate was 38.4% (95% confidence interval, 34.5%-42.8%). The median relative survival time was 4.3 years (95% confidence interval, 3.6%-5.2%). In the univariate Cox regression analysis, prognostic significances for age, stage, residual tumor, histopathologic subtype of serous cystadenocarcinoma, grade, CA-125, and ploidy status were seen. In the multivariate analysis, age, stage, residual tumor after surgery, and postoperative CA-125 were of prognostic significance. In conclusion, 4 major prognostic factors were found for EOC in this population-based cohort study that also presents nearly accurate long-term survival owing to the nonselective nature and completeness regarding patients and follow-up of the study.

Importance of vesicle proteins in the diagnosis and treatment of neuroendocrine tumors.

We have analyzed the expression of synaptic vesicle proteins in human neuroendocrine tumors and the potential use of vesicle proteins in the diagnosis and treatment of neuroendocrine tumors. Biopsies from endocrine and nonendocrine tumors of the gastrointestinal tract, pancreas, and adrenals were examined by immunocytochemistry using antibodies against synaptic vesicle protein 2 (SV2), vesicular monoamine transporter 1 and 2 (VMAT1 and 2), and neuroendocrine secretory protein 55 (NESP55). SV2 was expressed in all endocrine tumors of the gastrointestinal tract and pancreas as well as in gastrointestinal stromal tumors (GISTs). None of the adenocarcinomas expressed SV2. VMAT1 and 2 were expressed in amine-producing tumors of the gastrointestinal tract (ECL cell and EC cell carcinoids) and in a small number of peptide-producing pancreatic endocrine tumors. NESP55 was expressed in neuroblastomas and adrenal pheochromocytomas as well as in a subgroup of pancreatic endocrine tumors. The importance of VMAT1 and 2 for the uptake of 123I-MIBG in tumor cells was demonstrated. It was concluded that neuroendocrine tumors express multiple synaptic vesicle proteins that are useful in the histopathological diagnosis and classification of tumors. Vesicle proteins may prove to be useful for targeting tumor therapy.

Fluorescence in situ hybridisation analysis and ovarian histology of women with Turner syndrome presenting with Y-chromosomal material: a correlation between oral epithelial cells, lymphocytes and ovarian tissue.

The early detection of Y-chromosomal material in women with Turner syndrome (TS) is of great importance due to a relatively high risk of gonadal tumour development. Using fluorescence in situ hybridisation (FISH) analysis, we studied the presence of three different Y-specific sequences (SRY, Ycen and Yq12) in three different tissues (oral epithelial cells, lymphocytes and ovarian tissue) of twelve TS women. We have also described their ovarian histology. Two of the women (17%) had gonadal tumours. In five women where ovarian tissue was available, the presence of Y-chromosomal material in oral epithelial cells and lymphocytes correlated to the presence of Y-chromosomal material in the gonads. We therefore conclude that FISH analysis of oral epithelial cells and/or lymphocytes is a valuable complement to karyotyping for the early detection of Y-chromosomal material in TS women.

Expression of synaptic vesicle protein 2 (SV2) in neuroendocrine tumours of the gastrointestinal tract and pancreas.

Identification of neuroendocrine differentiation in tumours has important implications for prognosis and therapy. The aim of the present study was to evaluate monoclonal antibodies against synaptic vesicle protein 2 (SV2) as histopathological markers for neuroendocrine differentiation in tumours of the gastrointestinal tract and pancreas. Paraffin blocks from 211 gastrointestinal tumours were examined by immunocytochemistry, using a monoclonal antibody against SV2. Virtually all endocrine tumours of the gastrointestinal tract (11/11 gastric, 53/53 ileal, 16/21 appendiceal, and 22/22 rectal) and pancreas (24/24) were positively labelled. SV2 labelling was also demonstrated in gastrointestinal pacemaker cell tumours (8/8), while adenocarcinomas of the gastrointestinal tract and pancreas were negative, with the exception of occasional adenocarcinomas demonstrating weak SV2 labelling (stomach 1/22, rectum 1/29, and pancreas 0/21). Western blotting of tumour biopsies confirmed expression of SV2 in endocrine tumours of the gastrointestinal tract and pancreas. No relationship was observed between SV2 expression in tumours and hormone production or malignant potential. In conclusion, SV2 is expressed in neuroendocrine tumours of the gastrointestinal tract and pancreas, but not in non-endocrine tumours. The SV2 monoclonal antibody can therefore be used as a general marker for neuroendocrine differentiation in gastrointestinal and pancreatic tumours.