Case report: intravenous leiomyomatosis with intracaval and intracardiac growth.

Background: Intravenous leiomyomatosis (IVL) is a rare, benign smooth muscle cell tumour that extends beyond the pelvis. These tumours grow within vascular channels and can progress to involve the heart and pulmonary vasculature. Case Summary: A 44-year-old female initially presented to her primary care physician for subacute bloating. In the weeks leading up to her presentation, she was in good health. On admission, computed tomography (CT) imaging of the abdomen and pelvis was notable for a mixed solid and cystic mass arising from the fundal myometrium with invasion into the inferior vena cava (IVC). Transthoracic echocardiogram (TTE) was notable for mobile mass in the right atrium originating from the IVC. The mass was further evaluated by cardiac magnetic resonance (CMR) imaging before a multidisciplinary, single-staged thoracoabdominal resection was performed. The procedure was well tolerated, and the entire mass was successfully removed without complication. Subsequently, pathological analysis of the resected tumour revealed benign smooth muscle cells, confirming the diagnosis of IVL. Discussion: Intravenous leiomyomatosis is a rare cause of right-sided cardiac tumours but should be considered in premenopausal females, even those with a prior history of hysterectomy. The clinical presentation of patients with IVL is varied and imaging including CMR, CT, and TTE to evaluate the tissue characteristics and source of the cardiac mass should be performed. Finally, while imaging revealing a freely mobile pelvic mass extending into the IVC and right heart chambers is strongly suggestive of IVL, definitive diagnosis requires pathological analysis of resected tissue.

Incidence and predictors of toxicity in the management of vulvar squamous cell carcinoma treated with radiation therapy.

Purpose/Objective: Given the rarity of vulvar cancer, data on the incidence of acute and late severe toxicity and patients' symptom burden from radiotherapy (RT) are lacking. Materials/Methods: This multi-center, single-institution study included patients with vulvar squamous cell carcinoma treated with curative intent RT between 2009 and 2020. Treatment-related acute and late grade ≥ 3 toxicities and late patient subjective symptoms (PSS) were recorded. Results: Forty-two patients with predominantly stage III/IV disease (n = 25, 59.5 %) were treated with either definitive (n = 25, 59.5 %) or adjuvant (n = 17, 40.5 %) external beam RT to a median dose of 64 Gy and 59.4 Gy, respectively. Five patients received a brachytherapy boost with a median total dose of 84.3 Gy in 2 Gy-equivalent dose (EQD2). Intensity-modulated RT was used in 37 (88.1 %) of patients, and 25 patients (59.5 %) received concurrent chemotherapy. Median follow-up was 27 months. Acute grade ≥ 3 toxicity occurred in 17 patients (40.5 %), including 13 (31.0 %) acute grade 3 skin events. No factors, including total RT dose (p = 0.951), were associated with acute skin toxicity. Eleven (27.5 %) patients developed late grade ≥ 3 toxicity events, including 10 (23.8 %) late grade ≥ 3 skin toxicity events. Patients with late grade ≥ 3 skin toxicity had a higher mean body-mass index (33.0 vs 28.2 kg/m2; p = 0.009). Common late PSS included vaginal pain (n = 15, 35.7 %), skin fibrosis (n = 10, 23.8 %), and requirement of long-term opiates (n = 12, 28.6 %). Conclusion: RT for vulvar cancer is associated with considerable rates of severe acute and late toxicity and PSS burden. Larger studies are needed to identify risk factors, explore toxicity mitigation strategies, and assess patient-reported outcomes.

Recurrent uterine inflammatory myofibroblastic tumor previously managed as leiomyosarcoma has sustained response to alectinib.

Soft tissue sarcomas encompass a wide range of histologic subtypes with varied clinical implications. The incorporation of comprehensive genetic profiling into clinical practice is refining our ability to make these distinctions in diagnosis to better reflect prognosis and clinical behavior of a tumor. In this report, we describe a case of recurrent inflammatory myofibroblastic tumor (IMT) of the uterus, initially diagnosed and managed as leiomyosarcoma. At the time of recurrence, the patient was found to have a TNS1-ALK rearrangement and was treated successfully with alectinib, a second-generation anaplastic lymphoma kinase (ALK)-inhibitor. She had a complete response by imaging six months after initiation of alectinib and remains without evidence of disease at 36 months follow-up. Pathology review in the setting of her known ALK fusion and the 2020 update to the World Health Organization Classification of Female Genital Tumors led to a change in diagnosis from leiomyosarcoma to IMT. Our case highlights the role of molecular testing in the diagnosis and management of uterine mesenchymal tumors and the efficacy of alectinib in this ALK-rearranged recurrent IMT of the uterus. Care must be taken to differentiate between IMT and other uterine mesenchymal tumors as this distinction can impact prognosis and management. Furthermore, this case adds to the growing body of evidence supporting the paradigm shift toward developing molecularly targeted therapies rather than disease site-specific treatments, especially in cases of recurrence as recommended by the National Comprehensive Cancer Network.

Clinical needs for transgender men in the gynecologic oncology setting.

Transgender men remain at risk for gynecologic malignancies, but are an underserved population. Members of the transgender community experience discrimination and have experiences that contribute to health disparities, including in gynecology and oncology. While efforts have been made within the United States to reduce inequalities experienced by members of this community, many needs in the clinical setting remain. Increased education and training among providers and healthcare professionals, and general improvements towards understanding barriers to health screening and health resource uptake may reduce some disparities. Additional research towards screening and cancer surveillance among this community will be necessary to understand any potential additional risks and survival disparities experienced by transgender men. This review focuses on barriers and clinical needs for transgender men in the gynecologic oncology setting, and suggestions for moving forward to improve care for this patient population.

Implementation of a restrictive blood transfusion protocol in a gynecologic oncology service.

OBJECTIVES: The purpose of this study was to evaluate the impact of a restrictive blood transfusion protocol in a postoperative gynecologic oncology population. The primary objective was the rate of blood transfusions after surgery before and after implementation of a restrictive transfusion protocol (from July 1st 2011 to December 30th 2016). Secondary outcomes were patient morbidity and included rates of surgical site infection, pneumonia, sepsis, unplanned intubation, prolonged ventilator use, renal insufficiency, acute renal failure, urinary tract infection, cerebral vascular accident, cardiac complications, venous thromboembolism, and death within 30 days of surgery, readmissions and length of stay. METHODS: A restrictive blood transfusion protocol was implemented by the gynecologic oncology service at a National Comprehensive Cancer Network designated Comprehensive Cancer Center on January 1st, 2014. The restrictive protocol required that no patient receive a blood transfusion for hemoglobin greater than 7.0 g/dL (or hematocrit greater than 21.0%) and that all red blood cells were administered in one unit increments followed by re-evaluation of blood parameters. Exceptions to this protocol were postoperative symptomatic anemia, intraoperative or day of surgery transfusion, active bleeding, postoperative severe sepsis, postoperative active coronary ischemia, and postoperative transfusion after 1.5 liter or greater blood loss. RESULTS: 1482 patients were identified for this study (755 in the pre-protocol group and 727 in the post-protocol group). Patients treated under the restrictive protocol had decreased rates of red blood cell transfusion (11.0% vs 5.9% p<0.001), superficial surgical site infection (7.7% vs 4.1% p=0.005), deep surgical site infection (2.3% vs 0.7% p=0.02), and median length of stay (3.0 days vs 2.0 days p<0.001). CONCLUSIONS: A restrictive blood transfusion protocol is associated with reductions in the rates of blood transfusions and postoperative morbidity with a 46.8% reduction in superficial surgical site infection and a 69.6% decrease in deep surgical site infection in the gynecologic oncology patient population.

Prognostic impact of adjuvant chemotherapy treatment intensity for ovarian cancer.

OBJECTIVE: We aimed to investigate the prognostic impact of duration of first-line chemotherapy administration in patients with epithelial ovarian cancer (EOC). METHODS: Chemotherapy records were abstracted from the electronic medical record. Patients with on-time completion (105 days) were compared to patients finishing early (<105 days), delays of 1-4 weeks, or >4 weeks. For 222 women with stage IIIC/IV, stage-stratified estimates of progression-free survival (PFS) and overall survival (OS) were compared. A delay sub-study was performed with outliers removed. Each week of delay was correlated with the change in PFS and OS to identify time points associated with change in outcome. RESULTS: Most women had on-time completion of chemotherapy (23.6%) or a treatment delay of ≤4 weeks (21.8%); 21.6% of women experienced a delay longer than 4 weeks. R0 resection at initial debulking (OR = 1.99, 95%CI: 1.18-3.36, p = 0.010) and RECIST complete response (OR = 4.88, 95%CI: 2.47-10.63, p<0.001) were strongly associated with on-time completion. Patients with on-time completion and < 1 month delay had similar median survivals of 43.1 months (lower 95% CI bound 33.7 months) and 44.5 months (lower bound 37.0, p = 0.93). Women with >1 month delay had decreased median survival of 18.1 months (14.7-24.9 months), while women with short intervals survived 35.0 months (95%CI: 21.8-49.8 months). Short-term delays lead to progressively decreasing OS. This was significantly different from the on-schedule survival estimate after 6 weeks of delay. CONCLUSIONS: On-time completion of chemotherapy correlates with increased survival and higher complete response rates. Increasing delays in chemotherapy completion were associated with decreased survival.

Adoptive cell transfer using autologous tumor infiltrating lymphocytes in gynecologic malignancies.

During the last decade, the field of cancer immunotherapy has been entirely transformed by the development of new and more effective treatment modalities with impressive response rates and the prospect of long survival. One of the major breakthroughs is adoptive cell transfer (ACT) based on autologous T cells derived from tumor-infiltrating lymphocytes (TILs). TIL-based ACT is a highly personalized cancer treatment. T cells are harvested from autologous fresh tumor tissues, and after ex vivo activation and extensive expansion, are reinfused to patients. TIL-based therapies have only been offered in small phase I/II studies in a few centers given the highly specialized care required, the complexity of TIL production and the very intensive nature of the three-step treatment protocol. The treatment includes high-dose lymphodepleting chemotherapy, the infusion of the expanded and activated T cells and interleukin-2 (IL-2) injections to increase survival of the T cells. Despite the limited data on ACT, the small published studies consistently confirm an impressive clinical response rate of up to 50% in metastatic melanoma patients, including a significant proportion of patients with durable complete response. These remarkable results justify the need for larger clinical trials in other solid tumors, including gynecologic malignancies. In this review we provide an overview of the current clinical results, future applications of TIL-based ACT in gynecologic malignancies, and on risks and challenges associated with modern T cell therapy.

Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau.

Recurrent ovarian cancer (OvCa) is thought to result in part from the inability to eliminate rare quiescent cancer stem cells (CSCs) that survive cytotoxic chemotherapy and drive tumor resurgence. The Sialyl-Thomsen-nouveau antigen (STn) is a carbohydrate moiety present on protein markers of CSCs in pancreatic, colon, and gastric malignancies. We have demonstrated that human OvCa cell lines contain varying levels of cells that independently express either STn or the ovarian CSC marker CD133. Here we determine co-expression of STn and CD133 in a subset of human OvCa cell lines. Analyses of colony and sphere forming capacity and of response to standard-of-care cytotoxic therapy suggest a subset of OvCa STn+ cells display some CSC features. The effect of the anti-STn antibody-drug conjugates (ADCs) S3F-CL-MMAE and 2G12-2B2-CL-MMAE on OvCa cell viability in vitro and in vivo was also assessed. Treatment with S3F-CL-MMAE reduced the viability of two of three OvCa cell lines in vitro and exposure to either S3F-CL-MMAE or 2G12-2B2-CL-MMAE reduced OVCAR3-derived xenograft volume in vivo, depleting STn+ tumor cells. In summary, STn+ cells demonstrate some stem-like properties and specific therapeutic targeting of STn in ovarian tumors may be an effective clinical strategy to eliminate both STn+ CSC and STn+ non-CSC populations.

Anthropometric characteristics and ovarian cancer risk and survival.

PURPOSE: Multiple studies have examined the role of anthropometric characteristics in ovarian cancer risk and survival; however, their results have been conflicting. We investigated the associations between weight change, height and height change and risk and outcome of ovarian cancer using data from a large population-based case-control study. METHODS: Data from 699 ovarian cancer cases and 1,802 controls who participated in the HOPE study were included. We used unconditional logistic regression adjusted for age, race, number of pregnancies, use of oral contraceptives, and family history of breast or ovarian cancer to examine the associations between self-reported height and weight and height change with ovarian cancer risk. Cox proportional hazards regression models adjusted for age and stage were used to examine the association between the exposure variables and overall and progression-free survival among ovarian cancer cases. RESULTS: We observed an increased risk of ovarian cancer mortality and progression for gaining more than 20 pounds between ages 18-30, HR 1.36; 95% CI 1.05-1.76, and HR 1.31; 95% CI 1.04-1.66, respectively. Losing weight and gaining it back multiple times was inversely associated with both ovarian cancer risk, OR 0.78; 95% CI 0.63-0.97 for 1-4 times and OR 0.73; 95% CI 0.54-0.99 for 5-9 times, and mortality, HR 0.63; 95% CI 0.40-0.99 for 10-14 times. Finally, being taller during adolescence and adulthood was associated with increased risk of mortality. Taller stature and weight gain over lifetime were not related to ovarian cancer risk. CONCLUSIONS: Our results suggest that height and weight and their change over time may influence ovarian cancer risk and survival. These findings suggest that biological mechanisms underlying these associations may be hormone driven and may play an important role in relation to ovarian carcinogenesis and tumor progression.

Ultrarestrictive Opioid Prescription Protocol for Pain Management After Gynecologic and Abdominal Surgery.

Importance: Opioids are routinely prescribed for postoperative home pain management for most patients in the United States, with limited evidence of the amount needed to be dispensed. Opioid-based treatment often adversely affects recovery. Prescribed opioids increase the risk of chronic opioid use, abuse, and diversion and contribute to the current opioid epidemic. Objective: To evaluate whether after hospital discharge, postsurgical acute pain can be effectively managed with a markedly reduced number of opioid doses. Design, Setting, and Participants: In this case-control cohort study, an ultrarestrictive opioid prescription protocol (UROPP) was designed and implemented from June 26, 2017, through June 30, 2018, at a single tertiary-care comprehensive cancer center. All patients undergoing gynecologic oncology surgery were included. Patients undergoing ambulatory or minimally invasive surgery (laparoscopic or robotic approach) were not prescribed opioids at discharge unless they required more than 5 doses of oral or intravenous opioids while in the hospital. Patients who underwent a laparotomy were provided a 3-day opioid pain medication supply at discharge. Main Outcomes and Measures: Total number of opioid pain medications prescribed in the 60-day perioperative period, requests for opioid prescription refills, and postoperative pain scores and complications were evaluated. Factors associated with increased postoperative pain, preoperative and postoperative pain scores, inpatient status, prior opioid use, and all opioid prescriptions within the 60-day perioperative window were monitored among the case patients and compared with those from consecutive control patients treated at the center in the 12 months before the UROPP was implemented. Results: Patient demographics and procedure characteristics were not statistically different between the 2 cohorts of women (605 cases: mean [SD] age, 56.3 [14.5] years; 626 controls: mean [SD] age, 55.5 [13.9] years). The mean (SD) number of opioid tablets given at discharge after a laparotomy was 43.6 (17.0) before implementation of the UROPP and 12.1 (8.9) after implementation (P < .001). For patients who underwent laparoscopic or robotic surgery, the mean (SD) number of opioid tablets given at discharge was 38.4 (17.4) before implementation of the UROPP and 1.3 (3.7) after implementation (P < .001). After ambulatory surgery, the mean (SD) number of opioid tablets given at discharge was 13.9 (16.6) before implementation of the UROPP and 0.2 (2.1) after implementation (P < .001). The mean (SD) perioperative oral morphine equivalent dose was reduced to 64.3 (207.2) mg from 339.4 (674.4) mg the year prior for all opioid-naive patients (P < .001). The significant reduction in the number of dispensed opioids was not associated with an increase the number of refill requests (104 patients [16.6%] in the pre-UROPP group vs 100 patients [16.5%] in the post-UROPP group; P = .99), the mean (SD) postoperative visit pain scores (1.1 [2.2] for the post-UROPP group vs 1.4 [2.3] for pre-UROPP group; P = .06), or the number of complications (29 cases [4.8%] in the post-UROPP group vs 42 cases [6.7%] in the pre-UROPP group; P = .15). Conclusions and Relevance: Implementation of a UROPP was associated with a significant decrease in the overall amount of opioids prescribed to patients after gynecologic and abdominal surgery at the time of discharge for all patients, and for the entire perioperative time for opioid-naive patients without changes in pain scores, complications, or medication refill requests.

History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report.

BACKGROUND: Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. METHODS: We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer. RESULTS: Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97-1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19-3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03-1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival. CONCLUSIONS: In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.

Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer.

OBJECTIVE: The presence of miliary disease during initial ovarian cancer debulking may reflect a distinct mode of peritoneal spread independent from size-based tumor staging and may explain variation in response to treatment and survival outcomes. To infer the prevalence, presentation and clinical implications of miliary disease we reviewed existing surgical records. METHODS: Reports were available for 1008 primary debulking surgeries for ovarian, primary peritoneal or fallopian tube cancer between 2001 and 2015 (685 reports from 2005 to 2015). Clinical outcome data was available for 938 patients. We analyzed a high-stage sub-cohort for survival (N=436). RESULTS: Most records were evaluable for miliary disease (761/938); for these, the miliary phenotype was highly prevalent (249/761, 32.7%) and often accompanied by ascites (185/249, 74%). While optimal debulking rates were unaffected by miliary disease, total resection (R0) rates were poorer. Liver, stomach, spleen or bladder appeared to be sporadically involved while the omentum, mesentery, bowel, peritoneum and diaphragm were affected simultaneously (Spearman rho>0.5). Overall, miliary disease was associated with worse progression free survival, overall survival, and time from relapse to death independent of stage. Survival effects were particularly strong for Stage IV disease where median overall survival varied by over 30months (log-rank p=0.002). CONCLUSIONS: Miliary disease is an identifiable surgical phenotype reflecting a distinct clinical trajectory that adds prognostic information to standard disease burden-based staging. These findings should permit further retrospective investigation in a wider cohort and prompt the consideration of prospective structured operative reporting standards and treatment strategies.

Treatment of Advanced Malignant Uterine Perivascular Epithelioid Cell Tumor with mTOR Inhibitors: Single-institution Experience and Review of the Literature.

Uterine perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors. Many have malignant behavior, and no successful treatment strategy has been established. Identification of mutations in the tuberous sclerosis 1 (TSC1) and TSC2 genes producing constitutive activation of the mammalian target of rapamycin (mTOR) pathway presents an opportunity for targeted therapy. Patients with advanced malignant uterine PEComa treated with mTOR inhibitors were identified and records were retrospectively reviewed for treatment response based on radiographic assessment. Three patients with advanced uterine PEComas underwent debulking surgery followed by mTOR inhibitor therapy; two had a complete response to therapy and disease in one patient progressed. CONCLUSION: Given the absence of effective therapies for malignant uterine PEComas, targeting the mTOR pathway is a logical strategy to pursue given the known pathobiology involving the Tuberous Sclerosis complex. Treatment of malignant uterine PEComas with mTOR inhibitors was effective in two out of three patients after surgical resection, with durable response.

Patterns of care, predictors and outcomes of chemotherapy for uterine carcinosarcoma: a National Cancer Database analysis.

OBJECTIVE: Evaluate rates of chemotherapy and radiotherapy delivery in the treatment of uterine carcinosarcoma, and compare clinical outcomes of treated and untreated patients. METHODS: The National Cancer Database was queried to identify patients diagnosed with uterine carcinosarcoma between 2003 and 2011. The impact of chemotherapy on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. RESULTS: A total of 10,609 patients met study eligibility criteria. Stages I, II, III, and IV disease accounted for 2997 (28.2%), 642 (6.1%), 2037 (19.2%), and 1316 (12.4%) of the study population, respectively. Most patients (91.0%) underwent definitive surgery, and lymphadenectomy was performed in 68.7% of the patients. Chemotherapy was administered in 2378 (22.4%) patients, radiotherapy to 2196 (20.7%), adjuvant chemo-radiation to 1804 (17.0%), and 4231 (39.9%) of women did not received adjuvant therapy. Utilization of chemotherapy became more frequent over time. Over the entire study period, after adjusting for race, period of diagnosis, facility location, facility type, insurance provider, stage, age, treatment modality, lymph node dissection, socioeconomic status, and comorbidity index, there was an association between treatment modality and survival. The lowest hazard ratio observed was in patients that received chemo-radiation. The strongest quantitative predictor of death was stage at the time of diagnosis. In addition, surgical treatment, lymph node dissection, most recent time-periods, lower comorbidity index, and higher socioeconomic status were associated with improved survival. CONCLUSION: The overall rates of chemotherapy use have increased over time. Adjuvant chemotherapy and chemo-radiation were associated with improved survival.

Genome-wide comparison of paired fresh frozen and formalin-fixed paraffin-embedded gliomas by custom BAC and oligonucleotide array comparative genomic hybridization: facilitating analysis of archival gliomas.

Array comparative genomic hybridization (aCGH) is a powerful tool for detecting DNA copy number alterations (CNA). Because diffuse malignant gliomas are often sampled by small biopsies, formalin-fixed paraffin-embedded (FFPE) blocks are often the only tissue available for genetic analysis; FFPE tissues are also needed to study the intratumoral heterogeneity that characterizes these neoplasms. In this paper, we present a combination of evaluations and technical advances that provide strong support for the ready use of oligonucleotide aCGH on FFPE diffuse gliomas. We first compared aCGH using bacterial artificial chromosome (BAC) arrays in 45 paired frozen and FFPE gliomas, and demonstrate a high concordance rate between FFPE and frozen DNA in an individual clone-level analysis of sensitivity and specificity, assuring that under certain array conditions, frozen and FFPE DNA can perform nearly identically. However, because oligonucleotide arrays offer advantages to BAC arrays in genomic coverage and practical availability, we next developed a method of labeling DNA from FFPE tissue that allows efficient hybridization to oligonucleotide arrays. To demonstrate utility in FFPE tissues, we applied this approach to biphasic anaplastic oligoastrocytomas and demonstrate CNA differences between DNA obtained from the two components. Therefore, BAC and oligonucleotide aCGH can be sensitive and specific tools for detecting CNAs in FFPE DNA, and novel labeling techniques enable the routine use of oligonucleotide arrays for FFPE DNA. In combination, these advances should facilitate genome-wide analysis of rare, small and/or histologically heterogeneous gliomas from FFPE tissues.

The predominant WT1 isoform (+KTS) encodes a DNA-binding protein targeting the planar cell polarity gene Scribble in renal podocytes.

WT1 encodes a tumor suppressor first identified by its inactivation in Wilms' Tumor. Although one WT1 splicing variant encodes a well-characterized zinc finger transcription factor, little is known about the function of the most prevalent WT1 isoform, whose DNA binding domain is disrupted by a three-amino acid (KTS) insertion. Using cells that conditionally express WT1(+KTS), we undertook a genome-wide chromatin immunoprecipitation and cloning analysis to identify candidate WT1(+KTS)-regulated promoters. We identified the planar cell polarity gene Scribble (SCRB) as the first WT1(+KTS) target gene in podocytes of the kidney. WT1 and SCRB expression patterns overlap precisely in developing renal glomeruli of mice, and WT1(+KTS) binds to a 33-nucleotide region within the Scribble promoter in mouse and human cell lines and kidneys. Together, our results support a role for the predominant WT1(+KTS) isoform in transcriptional regulation and suggest a link between the WT1-dependent tumor suppressor pathway and a key component of the planar cell polarity pathway.