Opportunistic Salpingectomy Between 2017 and 2020: A Descriptive Analysis.

OBJECTIVES: Opportunistic salpingectomy (OS) is the removal of fallopian tubes during another pelvic surgery for the purpose of ovarian cancer prevention. Herein, we describe the rates of OS at the time of hysterectomy and tubal sterilization between 2017 and 2020. METHODS: This study uses the Canadian Institute of Health Information's Discharge Abstract Database and National Ambulatory Care Reporting System for all Canadian provinces and territories except for Quebec between the fiscal years 2017 and 2020. A descriptive analysis on all people aged 15 years and older who had hysterectomies or tubal sterilizations was conducted to determine the proportion of hysterectomies that included bilateral salpingectomy (OS) and the proportion of tubal sterilizations that were OS compared to tubal ligation. RESULTS: There were 174 006 people included in the study. The proportion of hysterectomies that included OS increased from 31.7% in 2017 to 39.9% by 2020. With respect to tubal sterilizations, rates of OS increased from 26.3% of all tubal sterilizations in 2017 to 42.5% in 2020. British Columbia remained the jurisdiction with the highest rates of OS, but rates increased significantly in many jurisdictions, particularly at the time of tubal sterilization. CONCLUSION: The rates of OS have continued to increase in all Canadian jurisdictions following the official Society of Obstetricians and Gynaecologists of Canada recommendation to consider OS in 2015. Assuming that all tubal ligations could have been OS and 75% of hysterectomies with ovarian conservation could have included OS, our data indicate 76 932 missed opportunities for ovarian cancer prevention.

HPV-independent Differentiated Vulvar Intraepithelial Neoplasia (dVIN) is Associated With an Aggressive Clinical Course.

Differentiated vulvar intrapeithelial neoplasia (dVIN) is an human papillomavirus (HPV)-independent precursor of squamous cell carcinoma (SCC), and the aim of this study was to better characterize its natural history. Cases of dVIN were identified from the pathology archives. Outcomes of patients with dVIN only, without associated invasive SCC, were compared with a cohort of patients with high-grade squamous intraepithelial lesion [HSIL(VIN3)]. Eighteen patients diagnosed with dVIN with adjacent invasive SCC (SCC/dVIN) and 7 patients with dVIN only, without invasive carcinoma, were identified. Mean age in both cohorts was 75 yr. All lesions but 1 were unifocal. In 35% of SCC/dVIN cases the surgical resection margins were positive for SCC, with 75% and 60% having margins positive for dVIN in the SCC/dVIN and dVIN-only cohorts, respectively. In total, 23/25 women with dVIN only or dVIN/SCC, for whom there was follow-up information, experienced either progression to or recurrence of invasive SCC, respectively, at a median of 1.1 yr, including all but 1 case of dVIN only, where the median time of progression to invasive SCC was 1.9 yr. A total of 22/25 women died of disease with a median overall survival of 3.4 yr. The outcome (i.e. progression to invasive carcinoma) of patients with dVIN only was significantly worse than that of a comparison group of 18 patients with HSIL(VIN3) (progression-free survival log-rank, P<0.001; disease-specific survival, P=0.04; overall survival, P=0.01). Six of 7 patients with dVIN only developed invasive carcinoma on follow-up, compared with 0 of 18 patients with HSIL(VIN3). The diagnosis of dVIN indicates the presence of a high-risk human papillomavirus-negative precursor of invasive SCC. These patients are likely to progress to invasive carcinoma over a relatively short period, at which point their prognosis is guarded.

Fluorescence confocal endomicroscopy of the cervix: pilot study on the potential and limitations for clinical implementation.

Current diagnostic capabilities and limitations of fluorescence endomicroscopy in the cervix are assessed by qualitative and quantitative image analysis. Four cervical tissue types are investigated: normal columnar epithelium, normal and precancerous squamous epithelium, and stromal tissue. This study focuses on the perceived variability within and the subtle differences between the four tissue groups in the context of endomicroscopic in vivo pathology. Conclusions are drawn on the general ability to distinguish and diagnose tissue types, on the need for imaging depth control to enhance differentiation, and on the possible risks for diagnostic misinterpretations.

Diffuse optical microscopy for quantification of depth-dependent epithelial backscattering in the cervix.

A fiber optic imaging approach is presented using structured illumination for quantification of almost pure epithelial backscattering. We employ multiple spatially modulated projection patterns and camera-based reflectance capture to image depth-dependent epithelial scattering. The potential diagnostic value of our approach is investigated on cervical ex vivo tissue specimens. Our study indicates a strong backscattering increase in the upper part of the cervical epithelium caused by dysplastic microstructural changes. Quantization of relative depth-dependent backscattering is confirmed as a potentially useful diagnostic feature for detection of precancerous lesions in cervical squamous epithelium.

Costs and benefits of opportunistic salpingectomy as an ovarian cancer prevention strategy.

OBJECTIVE: To conduct a cost-effectiveness analysis of opportunistic salpingectomy (elective salpingectomy at hysterectomy or instead of tubal ligation). METHODS: A Markov Monte Carlo simulation model estimated the costs and benefits of opportunistic salpingectomy in a hypothetical cohort of women undergoing hysterectomy for benign gynecologic conditions or surgical sterilization. The primary outcome measure was the incremental cost-effectiveness ratio. Effectiveness was measured in terms of life expectancy gain. Sensitivity analyses accounted for uncertainty around various parameters. Monte Carlo simulation estimated the number of ovarian cancer cases associated with each strategy in the Canadian population. RESULTS: Salpingectomy with hysterectomy was less costly ($11,044.32 ± $1.56) than hysterectomy alone ($11,206.52 ± $29.81) or with bilateral salpingo-oophorectomy ($12,626.84 ± $13.11) but more effective at 21.12 ± 0.02 years compared with 21.10 ± 0.03 and 20.94 ± 0.03 years, representing average gains of 1 week and 2 months, respectively. For surgical sterilization, salpingectomy was more costly ($9,719.52 ± $3.74) than tubal ligation ($9,339.48 ± $26.74) but more effective at 22.45 ± 0.02 years compared with 22.43 ± 0.02 years (average gain of 1 week) with an incremental cost-effectiveness ratio of $27,278 per year of life gained. Our results were stable over a wide range of costs and risk estimates. Monte Carlo simulation predicted that salpingectomy would reduce ovarian cancer risk by 38.1% (95% confidence interval [CI] 36.5-41.3%) and 29.2% (95% CI 28.0-31.4%) compared with hysterectomy alone or tubal ligation, respectively. CONCLUSION: Salpingectomy with hysterectomy for benign conditions will reduce ovarian cancer risk at acceptable cost and is a cost-effective alternative to tubal ligation for sterilization. Opportunistic salpingectomy should be considered for all women undergoing these surgical procedures.

Opportunistic salpingectomy: uptake, risks, and complications of a regional initiative for ovarian cancer prevention.

OBJECTIVE: The purpose of this study was to assess the uptake and perioperative safety of bilateral salpingectomy (BS) as an ovarian cancer risk-reduction strategy in low-risk women after a regional initiative that was aimed at general gynecologists in the province of British Columbia, Canada. STUDY DESIGN: This population-based retrospective cohort study evaluated 43,931 women in British Columbia from 2008-2011 who underwent hysterectomy that was performed with and without BS or bilateral salpingo-oophorectomy or who underwent surgical sterilization by means of BS or tubal ligation. Parameters that were examined include patient age, operating time, surgical approach, indication, length of hospital stay, and perioperative complications. RESULTS: There was an increase in the uptake of hysterectomy with BS (5-35%; P < .001) and BS for sterilization (0.5-33%; P < .001) over the study period, particularly in women <50 years old. Minimal additional surgical time is required for hysterectomy with BS (16 minutes; P < .001) and BS for sterilization (10 minutes; P < .001) compared with hysterectomy alone or tubal ligation, respectively. No significant differences were observed in the risks of hospital readmission or blood transfusions in women who underwent hysterectomy with BS (adjusted odds ratio [aOR], 0.91; 95% confidence interval [CI], 0.75-1.10; and aOR, 0.86; 95% CI, 0.67-1.10, respectively) or BS for sterilization (aOR, 0.8; 95% CI, 0.56-1.21; and aOR, 0.75; 95% CI, 0.32-1.73, respectively). From 2008-2011 the proportion of hysterectomies with BS performed by open laparotomy decreased from 77-44% with uptake in laparoscopic, vaginal, and combined procedures (P < .001). CONCLUSION: After our 2010 educational initiative, there has been a shift in surgical paradigm in our province. This cancer prevention approach does not increase the risk of operative/perioperative complications and appears both feasible and safe.

Exploring colposcopists' attitudes towards use of HPV testing as a primary screening tool for cervical cancer in British Columbia.

OBJECTIVE: To examine colposcopists' attitudes regarding human papillomavirus (HPV) DNA testing as a primary screening tool for cervical cancer. METHODS: Questionnaires administered in 2010 and 2011 during workshops in British Columbia elicited colposcopists' attitudes using a series of five-point Likert-style scales (strongly disagree to strongly agree) and binary (yes/no) response questions. The frequency of "agree" or "strongly agree" was used to characterize attitudes. Regression analyses examined statistically significant changes in attitudes after the 2010 workshop. RESULTS: Responses generally indicated positive changes in attitudes toward HPV testing. Statistically significant changes after the 2010 workshop were observed for the items relating to strong agreement that HPV is a necessary cause of cervical cancer (39% increase; P < 0.001) and the likelihood of openly advocating for HPV testing (19% increase; P < 0.04). In 2010, 40% of colposcopists stated that four years between HPV tests is too long, and in 2011, 53% did so. CONCLUSION: Colposcopists are viewed as opinion leaders and will have a critical role in implementing HPV testing in BC; our study obtained responses from 73% (2010) and 84% (2011) of BC-registered colposcopists. Colposcopists were in favour of HPV testing for primary screening for cervical cancer but did not support an extended interval for HPV testing, which suggests future knowledge translation workshops are crucial. We found that knowledge translation workshops can be an effective approach for translating evidence on screening and screening practices.

Objectif : Examiner les attitudes des colposcopistes à l'égard du dépistage de l'ADN du virus du papillome humain (VPH) à titre d'outil principal de dépistage du cancer du col utérin. Méthodes : Des questionnaires administrés en 2010 et en 2011 dans le cadre d'ateliers offerts en Colombie-Britannique se sont penchés sur les attitudes des colposcopistes au moyen de séries d'échelles en cinq points de type Likert (de « fortement en désaccord ¼ à « fortement en accord ¼) et de questions à réponse binaire (oui / non). La fréquence des réponses « en accord ¼ ou « fortement en accord ¼ a été utilisée pour caractériser les attitudes. Des analyses de régression ont examiné les modifications significatives sur le plan statistique en ce qui concerne les attitudes à la suite de l'atelier de 2010. Résultats : Les réponses ont généralement indiqué des modifications positives en ce qui concerne les attitudes envers le dépistage du VPH. À la suite de l'atelier de 2010, des modifications significatives sur le plan statistique ont été constatées pour ce qui est des articles liés au fait d'être fortement en accord avec la déclaration voulant que le VPH constitue une cause nécessaire du cancer du col utérin (hausse de 39 %; P < 0,001), ainsi que pour ce qui est de la probabilité de plaider ouvertement en faveur du dépistage du VPH (hausse de 19 %; P < 0,04). En 2010, 40 % des colposcopistes ont déclaré qu'un délai de quatre ans entre les tests de dépistage du VPH était trop long; en 2011, 53 % ont fait une telle déclaration. Conclusion : Les colposcopistes sont perçus comme étant des leaders d'opinion; ils joueront donc un rôle crucial dans la mise en œuvre du dépistage du VPH en Colombie-Britannique. Notre étude a obtenu des réponses de la part de 73 % (2010) et de 84 % (2011) des colposcopistes inscrits en C.-B. Les colposcopistes étaient en faveur de l'utilisation du dépistage du VPH aux fins du dépistage primaire du cancer du col utérin, mais ne soutenaient pas la mise en œuvre d'un intervalle prolongé dans le cadre du dépistage du VPH, ce qui semble indiquer que la tenue de futurs ateliers de transfert des connaissances s'avère cruciale. Nous avons constaté que les ateliers de transfert des connaissances peuvent constituer une approche efficace pour assurer l'application des résultats de recherche au dépistage et aux pratiques connexes.

The role of the fallopian tube in ovarian cancer.

High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian cancer. Research over the past decade has strongly suggested that "ovarian" HGSC arises in the epithelium of the distal fallopian tube, with serous tubal intraepithelial carcinomas (STICs) being detected in 5-10% of BRCA1/2 mutation carriers undergoing risk-reducing surgery and up to 60% of unselected women with pelvic HGSC. The natural history, clinical significance, and prevalence of STICs in the general population (ie, women without cancer and not at an increased genetic risk) are incompletely understood, but anecdotal evidence suggests that these lesions have the ability to shed cells with metastatic potential into the peritoneal cavity very early on. Removal of the fallopian tube (salpingectomy) in both the average and high-risk populations could therefore prevent HGSC, by eliminating the site of initiation and interrupting spread of potentially cancerous cells to the ovarian/peritoneal surfaces. Salpingectomy may also reduce the incidence of the 2 next most common subtypes, endometrioid and clear cell carcinoma, by blocking the passageway linking the lower genital tract to the peritoneal cavity that enables ascension of endometrium and factors that induce local inflammation. The implementation of salpingectomy therefore promises to significantly impact ovarian cancer incidence and outcomes.

Identification of novel therapeutic targets in microdissected clear cell ovarian cancers.

Clear cell ovarian cancer is an epithelial ovarian cancer histotype that is less responsive to chemotherapy and carries poorer prognosis than serous and endometrioid histotypes. Despite this, patients with these tumors are treated in a similar fashion as all other ovarian cancers. Previous genomic analysis has suggested that clear cell cancers represent a unique tumor subtype. Here we generated the first whole genomic expression profiling using epithelial component of clear cell ovarian cancers and normal ovarian surface specimens isolated by laser capture microdissection. All the arrays were analyzed using BRB ArrayTools and PathwayStudio software to identify the signaling pathways. Identified pathways validated using serous, clear cell cancer cell lines and RNAi technology. In vivo validations carried out using an orthotopic mouse model and liposomal encapsulated siRNA. Patient-derived clear cell and serous ovarian tumors were grafted under the renal capsule of NOD-SCID mice to evaluate the therapeutic potential of the identified pathway. We identified major activated pathways in clear cells involving in hypoxic cell growth, angiogenesis, and glucose metabolism not seen in other histotypes. Knockdown of key genes in these pathways sensitized clear cell ovarian cancer cell lines to hypoxia/glucose deprivation. In vivo experiments using patient derived tumors demonstrate that clear cell tumors are exquisitely sensitive to antiangiogenesis therapy (i.e. sunitinib) compared with serous tumors. We generated a histotype specific, gene signature associated with clear cell ovarian cancer which identifies important activated pathways critical for their clinicopathologic characteristics. These results provide a rational basis for a radically different treatment for ovarian clear cell patients.

The significance of surgical staging in intermediate-risk endometrial cancer.

OBJECTIVE: The objective was to evaluate rates of nodal disease in endometrial cancer within risk groups based on uterine factors, and to estimate the rate of potential undertreatment and impact on survival if nodal status was unknown. METHODS: This was a population-based retrospective cohort study of endometrioid-type endometrial cancer in British Columbia from 2005 to 2009. All women with a preoperative grade 2/3 cancer underwent hysterectomy, bilateral salpingo-oophorectomy (HBSO) and lymphadenectomy, and those with intermediate- or high-risk disease based on uterine factors after HBSO alone underwent secondary lymphadenectomy. We compared rates of node-positivity and potential undertreatment in each group if nodal status had been unknown (chi-square test), and estimated the survival benefit from lymphadenectomy. RESULTS: There were 222 women who underwent primary or secondary lymphadenectomy. Median age was 65 (range 38-86) and median number of lymph nodes was 10 (range 2-39). Of the 66 women with intermediate-risk disease (grade 1 or 2 tumor, deep myometrial invasion), 6 had nodal disease (9.1%) and received adjuvant chemotherapy. They remain disease-free after 24 months (range 8-55). They would not have qualified for chemotherapy based on uterine factors alone, and would have been undertreated compared to other risk groups (chi-square p=0.071). A 1% survival benefit was estimated from lymphadenectomy. CONCLUSION: Women with a grade 1 or 2 tumor and deep myometrial invasion have a 9% risk of nodal disease. Lymphadenectomy is significant for this subgroup as they would have been undertreated based on uterine risk factors alone, although the survival benefit is limited.

HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy.

BACKGROUND: The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification, and the potential for trastuzumab therapy in this histologic subtype of ovarian cancer. METHODS: HER2 status was tested in 33 mucinous carcinomas and 16 mucinous borderline ovarian tumors (BOT)). Five cases with documented recurrence and with tissue from the recurrence available for testing were analyzed to determine whether HER2 amplification status changed over time. Three prospectively identified recurrent mucinous ovarian carcinomas were assessed for HER2 amplification and patients received trastuzumab therapy with conventional chemotherapy. RESULTS: Amplification of HER2 was observed in 6/33 (18.2%) mucinous carcinomas and 3/16 (18.8%) BOT. HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence. The prospectively identified recurrent mucinous carcinomas showed overexpression and amplification of HER2; one patient's tumor responded dramatically to trastuzumab in combination with conventional chemotherapy, while another patient experienced an isolated central nervous system recurrence after trastuzumab therapy. CONCLUSION: HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance. Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression.

SV40 early genes induce neoplastic properties in serous borderline ovarian tumor cells.

OBJECTIVE: Serous borderline ovarian tumors (SBOT) are slow growing, noninvasive ovarian epithelial neoplasms, which tend to recur as low-grade invasive carcinomas (LGC) with a much worse prognosis. We investigated the molecular basis of this progression. METHODS: We established cultures of three SBOTs and one LGC from tumor biopsies, and inactivated p53, Rb and PP2A in the cells with SV40 large T (LT) and small T (ST) antigen. They were examined for cadherins by immunofluorescence and immunoblotting, invasiveness in Boyden chambers, motility by scratch-wound healing assay, anchorage independence by growth in agarose, and protease activity by gelatin zymography, immunoassay and colorimetry. Cells were overexpressed with N-cadherin using an adenovirus. RESULTS: Inactivation of p53, Rb and PP2A by SV40 LT/ST antigen resulted in greatly enhanced growth potential, invasiveness, motility and anchorage independence, and in epithelio-mesenchymal transition, as indicated by morphology and substitution of N-cadherin for E-cadherin. Overexpressed N-cadherin did not induce invasiveness of SBOT cells and there was no consistent change in protease activities, suggesting that these were not primary effectors of the enhanced neoplastic characteristics. Low passage LGC cells were more invasive than SBOT cells, but this difference disappeared with the introduction of LT/ST into the two cell types. CONCLUSION: Downregulation or inactivation of p53, Rb and/or PP2A plays a role in the progression from SBOT to invasive ovarian carcinomas.

Xenografts of primary human gynecological tumors grown under the renal capsule of NOD/SCID mice show genetic stability during serial transplantation and respond to cytotoxic chemotherapy.

OBJECTIVES: Human cancer tissue xenograft models may provide a more accurate reflection of tumor biology than cell lines. This study evaluates the genetic and phenotypic stability of primary human gynecological tumors grown as serially transplanted xenografts. The response to conventional chemotherapy and novel molecular targeted chemotherapy is assessed in one of the transplantable xenograft lines. METHODS: Fresh tumor was transplanted beneath the renal capsule of NOD/SCID mice. Transplantable tumor lines were derived from 5 tumors (4 ovarian carcinomas and 1 uterine sarcoma), and serially transplanted for 2-6 generations. Comparisons were made between primary tumor and corresponding transplantable xenografts by CGH array, immunohistochemistry, and BRCA mutation analysis. Transplantable xenografts created from known BRCA1 germline mutation carriers were analyzed for histopathologic response (tumor volume, apoptotic and mitotic indices) to combination carboplatin/paclitaxel and to PARP inhibitor (PJ34). RESULTS: Unsupervised hierarchical cluster analysis applied to a 287 feature CGH array demonstrated a low degree of intratumoral genetic variation in 4/5 cases, with greater degree of variation in the fifth case (clear cell ovarian carcinoma derived from an omental sample). Assessment of proliferation using MIB-1 staining was concordant between primary tumor and transplantable xenograft in all ovarian cancer cases. BRCA mutation analysis identified germline BRCA1 mutation for further testing and this xenograft showed a significant response to carboplatin/paclitaxel chemotherapy, including a decrease in tumor volume and proliferation but did not demonstrate a response to the poly (ADP-ribose) polymerase-1 inhibitor PJ34. CONCLUSIONS: Xenografts derived from gynecologic tumors can be serially transplanted and grown under renal capsule of NOD/SCID mice with minimal genetic change. This model may be used to study progression of tumors, identify therapeutic targets, and test treatment modalities in tumors with well-characterized abnormalities in genes of fundamental importance in ovarian carcinogenesis, such as loss of BRCA1.

Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities.

BACKGROUND: Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. METHODS: A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. RESULTS: Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumours were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. CONCLUSION: High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

Establishment of subrenal capsule xenografts of primary human ovarian tumors in SCID mice: potential models.

OBJECTIVE: To evaluate subrenal capsule xenografting of primary ovarian tumor tissues in mice for development of new ovarian cancer models. METHODS: Pieces (1 x 3 x 3 mm) of ovarian tumor specimens from patients were meticulously grafted under renal capsules of female NOD/SCID mice within 2 h of surgical removal. Tumor types included papillary serous adenocarcinomas, borderline and benign mucinous cystadenomas, granulosa cell tumors, a serous borderline tumor and a grade 3 mixed surface epithelial tumor of transitional and undifferentiated types. After 1-2 months, grafts were retrieved for comparison with original tissues. Hematoxylin and eosin (H&E) and immunohistochemical staining was carried out using tissue micro-arrays and CEA, B72.3, WT-1, OC125, keratin, inhibin, CK7, CK20, Cam5.2, and MIB-1 as markers. RESULTS: Tumor tissue engraftment rate was > 95%. Comparison of donor and post-graft tissues showed highly similar histopathological features; 91 +/- 5% concordance in immunostaining indicated major preservation of immunophenotypes in the xenografts for 30-60 days. There was a small, but significant, increase in MIB-1 proliferative index in xenografts compared to original specimens. CONCLUSIONS: Subrenal capsule xenografts of primary human ovarian tumors in SCID mice can retain major histopathological and immunohistochemical characteristics of the original tissues. The achievable, consistently high engraftment rate allows use of such xenografts as tools for studying a wide range of ovarian tumors, including granulosa cell tumors and benign, borderline, and malignant surface epithelial neoplasms. Potential applications include preclinical testing of patients' tumor responses to various chemotherapeutic regimens, evaluation of novel therapeutic agents, analysis of tumor progression at cellular and molecular levels, and identification of new therapeutic targets.

Advanced-stage serous borderline tumors of the ovary: a clinicopathological study of 49 cases.

There is controversy about patient outcomes and pathological parameters of prognostic significance in patients with stage II or stage III ovarian serous borderline tumors. Forty-nine cases of stage II and III ovarian serous borderline tumors were identified on review of the medical records at Vancouver Hospital and British Columbia Cancer Agency for the period from 1979 to 1996. Pathological features assessed included presence of micropapillary architecture, tumor cell DNA content (ploidy), and characteristics of the extraovarian implants, including invasiveness and mitotic activity. Clinical follow-up information (3-17 years of follow-up) was obtained for 48 patients. Fifteen patients had stage II tumors and 34 had stage III tumors. Fourteen patients experienced tumor recurrence 1 to 8 (mean 3.5) years after presentation and of these, six patients died of disease (2, 3, 4, 7, 10, and 11 years after presentation). Patients with gross residual disease, as assessed by the surgeon, more frequently experienced a recurrence compared with patients without gross residual disease, but this difference did not reach statistical significance (0.05