Papillary Serous Carcinoma Research Articles

The role of chemotherapy and radiation in AJCC surgical stage I uterine papillary serous carcinoma: A retrospective analysis of 4,970 patients

Objective: The aim of this study is to determine the role of chemotherapy and radiation in surgically staged I uterine papillary serous cancer (UPSC).

Prevalencia de carcinoma en pólipos endometriales resecados por histeroscopia.

La prevalencia de pólipos endometriales (PE) es alrededor de 24% en la población femenina general y entre 10 y 30% en aquellas con hemorragia uterina anormal. Son lesiones de crecimiento rápido que pueden transformarse en una neoplasia maligna. Objetivo: determinar la frecuencia de cáncer endometrial en pacientes con PE diagnosticados por histeroscopia. Metodología: serie de casos retrospectivos atendidos en el Hospital de San José, Bogotá, Colombia, de 2005 a 2014. Resultados: se analizaron en total 408 historias clínicas de pacientes con diagnóstico histopatológico de PE, 10 (2.4%) presentaron patología premaligna y 9 (2,2%) lesión maligna confirmada por microscopía (endometrioides 6, seroso papilar 2 y carcinosarcoma 1). Todas las pacientes con patología maligna tenían más de 60 años y estaban en posmenopausia. Cuatro eran nulíparas, ninguna consumía tamoxifeno ni medicamentos hormonales Conclusión: la prevalencia de carcinomas endometriales en PE diagnosticados a través de histeroscopia en mujeres posmenopáusicas fue de 7.7%. Estos datos son similares a los reportados en la literatura, por lo que recomendamos la implementación de histeroscopia para el tratamiento de todos los PE y su riguroso estudio histopatológico.

Uterine Papillary Serous Carcinoma Arising in a Polyp: A Multicenter Retrospective Analysis on 75 Patients.

The objectives of this study were to evaluate whether the international recommendations on the management of uterine papillary serous carcinoma arising in a polyp are uniformly followed in Italian Oncologic Centers and whether the strategy adopted is effective. Patients with uterine papillary serous carcinoma arising in a polyp and who had undergone a hysterectomy were identified in the 2003-2013 database of 7 Italian Gynecologic Oncology Centers. Clinical and pathologic characteristics and outcomes were compared between staging procedure types. Survival curves of the women were plotted using the Kaplan-Meier method and analyzed using Cox regression hazard model and the log-rank test. Associations between clinical parameters and the incidence of recurrence were assessed by generalized linear models and the Fisher test. A total of 75 patients met the inclusion criteria. Recurrence-free survival was affected positively by type of surgical staging and negatively by preoperative diagnosis of hypertension. The association between surgical staging and recurrence-free survival resulted significant at univariate survival analysis (P=0.048 and 0.045) and maintained a trend of significance (P=0.070) in multivariate analysis, whereas hypertension was demonstrated to be the principal influencing factor. The international recommendations on the management of uterine papillary serous carcinoma are not uniformly followed in daily practice, although the extension of the surgery seems to be associated with lower recurrence rates also when uterine papillary serous carcinoma is confined to a polyp or endometrial surface.

Sub-terahertz vibrational spectroscopy of ovarian cancer and normal control tissue for molecular diagnostic technology.

We introduce here recently developed highly resolved Sub-Terahertz resonance spectroscopy of biological molecules and cells combined with molecular dynamics (MD) computational analysis as a new approach for optical visualization and quantification of the presence of microRNAs, particularly the mir-200 family, as potential biomarkers in samples from tissue of epithelial ovarian cancers for disease early detection, analysis, prognosis and treatment.METHOD: A set of samples for this study was prepared from anonymized archival formalin-fixed, paraffin-embedded ovarian epithelial tissue containing regions of invasive neoplastic cells from cases of high-histologic grade serous papillary ovarian carcinoma. Control samples were normal mucosa from fallopian tubes of patients with no known malignancy. Spectroscopic characterization of tissue samples in this study was performed using a continuous wave, frequency domain automated spectrometer operating at room temperature in the spectral region of 310-500 GHz. The spectral results were compared with molecular dynamics simulations and absorption coefficient calculations utilized to predict the absorption spectra.RESULTS: The characteristic spectroscopic features in absorption spectra, particularly the presence of absorption peaks near 13cm-1 have been identified as cancer indicators. Tissue samples heterogeneity, reflected by diverse spectral signatures, provides additional, very specific information that may be used for identification of cancer subtypes, clinical behavior or sensitivity to specific therapies. Further work is warranted to determine if this signature can be detected in bio-fluids from ovarian cancer patients. If strongly correlated with cancer burden, it may then be investigated as a potential new biomarker for disease monitoring, and also perhaps as a biomarker for cancer screening.

Uterine papillary serous carcinoma: A rare type of endometrial carcinoma with worse outcomes

Introduction: Uterine papillary serous carcinoma (UPSC) is a clinically aggressive type of endometrial carcinoma. They represent about 10% of endometrial carcinomas and are responsible for 40% of deaths and recurrences associated with endometrial cancer. Patient Presentation: JM is a 75 year old woman who presented with eight months’ postmenopausal vaginal bleeding, loss of weight and low abdominal pain. Except for obesity and bilateral pitting edema, she had normal findings on physical examination. Management and Outcome: Pelvic ultrasound showed an intra-uterine mass of increased echo (4×4 cm) and a pelvic CT scan showed a bulky uterus bulky with prominent endometrium. Visual inspection with acetic acid and Lugol’s iodine was negative for cervical cancer whereas Pipelle biopsy indicated endometrial cancer. She had total hysterectomy with bilateral salpingo-oophorectomy. She is due to start chemotherapy. Conclusion: Even though endometrial biopsy using a Pipelle is highly sensitive for detection of high-grade endometrial carcinomas, it is less accurate at predicting UPSC. Patients undergoing surgery for endometrial cancer should therefore have a comprehensive surgical staging as the patient may have UPSC. Due to the risk of recurrence, adjuvant chemo-radiation should be administered after surgery. Keywords: Postmenopausal bleeding, Uterine papillary serous carcinoma, Edometrial serous carcinoma, Endometrial cancer.

Serous Papillary Carcinoma of Cervix: A Clinicopathological Dilemma

Serous papillary carcinoma of the cervix is a rare variant of the adenocarcinoma of the cervix with less than 50 cases reported worldwide. There are no clear guidelines for the management of this particular subtype, and the treatment is tailor-made based on retrospective analysis and the physician’s discretion. We present a case of locally advanced papillary serous cancer cervix that was managed radically with concurrent chemoradiotherapy and is presently disease free on follow-up.

Can morphometric analysis of the fallopian tube fimbria predict the presence of uterine papillary serous carcinoma (UPSC)?

Uterine serous papillary carcinoma (UPSC) is an aggressive tumor, often diagnosed as a metastatic disease and characterized by a high recurrence rate and poor prognosis. UPSC represents a distinct subtype of endometrial cancer which is different in clinical and pathological behaviors from endometrioid endometrial carcinoma (EEC) and resembles more to serous ovarian carcinoma. Since tumors of serous papillary of the ovary are hypothesized to stem from cells of the fallopian tube's fimbria, we hypothesized that UPSC may also origin in the fallopian tubes. In our previous study, using a novel method of computerized morphometry of the fimbrial epithelium we have found significant differences between fimbriae of healthy women and serous ovarian cancer patients. In this study we showed the presence of morphologic differences between twenty-four fimbriae from healthy women, and twenty six fimbriae from uterus cancer (13 from UPSC patients and 13 from EEC patients). All fimbriae reported by the pathologist as "normal" were subjected to a computerized histomorphometric analysis. Two-step method of computerized histomorphometry, i.e. Fast Fourier transformation (FFT) followed by a co-occurrence matrix analysis and an additional analysis of the nuclear symmetry of the tubal fimbrial epithelium were applied. Using these novel methods, we were able to show differences in the morphometric characteristics of the fimbriae in UPSC patients compared to EEC and healthy patients. It is yet to be determined the clinical significance of this observation.

Higher CXCL16 exodomain is associated with aggressive ovarian cancer and promotes the disease by CXCR6 activation and MMP modulation

Ovarian cancer (OvCa) is the leading cause of death from gynecological malignancies. Five-year survival rate of OvCa ranges from 30–92%, depending on the spread of disease at diagnosis. Role of chemokines is well appreciated in cancer, including OvCa. However, their precise role is understudied. Here, we show clinical and biological significance of CXCR6-CXCL16 and ADAM10 in OvCa. Expression of CXCR6 and N-terminal CXCL16 was significantly higher in serous carcinoma tissues compared to endometrioid. OvCa cells (SKOV-3 and OVCAR-3) also showed higher expression of CXCR6 than normal ovarian epithelial cells (IOSE-7576) while CXCL16 was higher in SKOV-3 than IOSE-7576. Furthermore, N-terminal CXCL16 was higher in conditioned media of OvCa cells than IOSE-7576. Compared to OVCAR-3, SKOV-3 cells, which had higher CXCL16, expressed significantly higher transcripts of ADAM10, a protease that cleaves CXCL16. OVCAR-3 cells showed higher CXCR6 specific migration whereas SKOV-3 cells showed more invasion. Difference in invasive potential of these cells was due to modulation of different MMPs after CXCL16 stimulation. Higher CXCR6 expression in serous papillary carcinoma tissues suggests its association with aggressive OvCa. Increased migration-invasion towards CXCL16 implies its role in metastatic spread. Therefore, CXCR6-CXCL16 axis could be used to differentiate between aggressive versus non-aggressive disease and as a target for better prognosis.

Human Ovarian Cancer Tumor Formation in Severe Combined Immunodeficient (SCID) Pigs.

Ovarian cancer (OvCa) is the most lethal gynecologic malignancy, with two-thirds of patients having late-stage disease (II-IV) at diagnosis. Improved diagnosis and therapies are needed, yet preclinical animal models for ovarian cancer research have primarily been restricted to rodents, for data on which can fail to translate to the clinic. Thus, there is currently a need for a large animal OvCa model. Therefore, we sought to determine if pigs, being more similar to humans in terms of anatomy and physiology, would be a viable preclinical animal model for OvCa. We injected human OSPC-ARK1 cells, a chemotherapy-resistant primary ovarian serous papillary carcinoma cell line, into the neck muscle and ear tissue of four severe combined immune deficient (SCID) and two non-SCID pigs housed in novel biocontainment facilities to study the ability of human OvCa cells to form tumors in a xenotransplantation model. Tumors developed in ear tissue of three SCID pigs, while two SCID pigs developed tumors in neck tissue; no tumors were detected in non-SCID control pigs. All tumor masses were confirmed microscopically as ovarian carcinomas. The carcinomas in SCID pigs were morphologically similar to the original ovarian carcinoma and had the same immunohistochemical phenotype based on expression of Claudin 3, Claudin 4, Cytokeratin 7, p16, and EMA. Confirmation that OSPC-ARK1 cells form carcinomas in SCID pigs substantiates further development of orthotopic models of OvCa in pigs.

Comparison of Conventional Cytology, Liquid-Based Cytology, and Cell Block in the Evaluation of Peritoneal Fluid in Gynecology Malignancies

Background: Peritoneal washing cytology has become an accepted method in evaluating gynecology malignancies. Objective: The aim of this work was to compare the conventional cytology, liquid-based cytology (LBC), and cell block in the evaluation of peritoneal fluid. Materials and Methods: A total of 48 cases with ovarian and uterine malignancy were included in this study. The age of the patients varied from 15 to 71 years. All the 48 cases were subjected to conventional smear, LBC, and cell block preparation. Results: The results of LBC and conventional methods were in line with all cytological criteria, except for the background (p = 0.045), but no significant difference was found regarding adequacy (p = 0.12), cellularity (p = 0.13), cell architecture (p = 0.751), nuclear details (p = 0.96), and cytoplasmic details (p = 0.32). The kappa correlation between conventional cytology and LBC, conventional cytology and cell block, and LBC and cell block was 0.769, 0.791, and 0.945, respectively. The most prevalent malignancy which led to peritoneal fluid involvement was papillary serous carcinoma of the ovary. Conclusion: Compared to conventional cytology, the liquid-based method had no significant superiority in the evaluation of the peritoneal fluid method, but the combined usage of smears and cell block improved the diagnostic accuracy of the peritoneal washing samples in different gynecological malignancies.

Survival outcomes of adjuvant radiotherapy and chemotherapy in women with stage I serous papillary and clear cell carcinoma of the endometrium: a Korean multicenter study.

ObjectiveTo compare the survival outcomes of adjuvant radiotherapy and chemotherapy in women with uterine-confined endometrial cancer with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CCC).MethodsMedical records of 80 women who underwent surgical staging for endometrial cancer were retrospectively reviewed. Stage I UPSC and CCC were pathologically confirmed after surgery. Survival outcomes were compared between the adjuvant radiotherapy and chemotherapy groups.ResultsFifty-four (67.5%) and 26 (32.5%) women had UPSC and CCC, respectively. Adjuvant therapy was administered to 59/80 (73.8%) women (25 radiotherapy and 34 chemotherapy). High preoperative serum cancer antigen-125 level (25.1±20.2 vs. 11.5±6.5 IU/mL, p<0.001), open surgery (71.2% vs. 28.6%, p=0.001), myometrial invasion (MI) ≥1/2 (33.9% vs. 0, p=0.002), and lymphovascular space invasion (LVSI; 28.8% vs. 4.8%, p=0.023) were frequent in women who received adjuvant therapy compared to those who did not. However, the histologic type, MI ≥1/2, and LVSI did not differ between women who received adjuvant radiotherapy and those who received chemotherapy. The 5-year progression-free survival (78.9% vs. 80.1%, p>0.999) and overall survival (77.5% vs. 87.8%, p=0.373) rates were similar between the groups. Neither radiotherapy (hazard ratio [HR]=1.810; 95% confidence interval [CI]=0.297–11.027; p=0.520) nor chemotherapy (HR=1.638; 95% CI=0.288–9.321; p=0.578) after surgery was independently associated with disease recurrence.ConclusionOur findings showed similar survival outcomes for adjuvant radiotherapy and chemotherapy in stage I UPSC and CCC of the endometrium. Further large study with analysis stratified by MI or LVSI is required.

Malignant ascites occurs most often in patients with high-grade serous papillary ovarian cancer at initial diagnosis: a retrospective analysis of 191 women treated at Bayreuth Hospital, 2006-2015.

Malignant ascites often develops in patients with ovarian cancer, but there is a lack of more detailed characterization of the different histological subtypes. Ascites specimens from patients with ovarian cancer who were treated at Bayreuth Hospital from 2006 to 2015, with follow-up until December 2016, were reevaluated retrospectively. A total of 191 women (mean age 64years, range 48-79) were included, of whom 180 (94.2%) had carcinoma, three (1.6%) had malignant mixed müllerian tumors (MMMTs), four (2.1%) had sex cord-stromal tumors (SCSTs), three (1.6%) had germ cell tumors (GCTs), and one (0.5%) had a sarcoma. The carcinoma group comprised 134 (70.1%) patients with high-grade serous papillary ovarian cancer, 17 (8.9%) with low-grade serous papillary ovarian cancer, 10 (5.3%) with mucinous carcinomas, nine (4.7%) with endometrioid carcinomas, six (3.1%) with clear cell carcinomas, and four (2.1%) with neuroendocrine tumors. The latter group consisted of two patients with mixed neuroendocrine-nonneuroendocrine tumors (MiNENs), one with only a small cell carcinoma (SCCO), and one with a mucinous carcinoid. The noncarcinomatous group of eight patients (4.2%) included three (1.6%) with Sertoli-Leydig cell tumor and mature cystic teratoma (MCT), one (0.5%) with a granulosa cell tumor, and one with a leiomyosarcoma. A statistically significant difference in the proportion of patients with malignant ascites was observed, at 17.7% (3/17) in those with low-grade serous papillary ovarian cancer and 91.8% (123/134) in those with high-grade serous papillary ovarian carcinomas. In both patients with MiNEN, the glandular tumor cell component was found in the ascites. Tumor cells were found in the ascitic fluid in 50% (5/10) of patients with mucinous ovarian carcinomas, 16.7% (1/6) of those with clear cell carcinomas, and 33.3% (1/3) of those with MMMTs. The two patients (2/3; 66.7%) with neoplastic squamous cell components in MCT and the only patient with a granulosa cell tumor in the SCST group (1/4; 25%) had malignant cell populations in the ascites, whereas patients with endometrioid cell carcinoma and leiomyosarcoma lacked tumor cells in the ascites. The malignant ascites was detected at the initial diagnosis in all 138 (100%) patients with ovarian neoplasms. High-grade serous papillary ovarian cancer was the main histological subtype most frequently found in ascites fluid in this series. The significant difference (P < 0.00001) in the malignancy rate in comparison with low-grade serous papillary carcinoma confirms the histological distinction between the two entities. Initial evidence of ovarian cancer in ascites fluid allows correct primary diagnosis in cytology specimens and is important for staging and prognosis.

Clinicopathological and survival analysis of uterine papillary serous carcinoma: a single institutional review of 106 cases.

ObjectivesThe objectives of this study were to analyze clinicopathological features and to investigate the prognostic determinants in patients with uterine papillary serous carcinoma (UPSC).Materials and methodsA cohort of 106 UPSC patients diagnosed and treated at Peking Union Medical College Hospital between 2000 and 2016 were retrospectively reviewed. The Kaplan–Meier method and Cox regression analysis were used for survival analysis. Differences between categorical data were calculated by using the chi-squared test.ResultsThe median follow-up was 29.0 months (range =2–170 months), with an overall recurrence rate of 35.8%. The coincidence rate between preoperative endometrial sampling and postoperative definitive pathology of hysteroscopy group was significantly higher than that of the dilation and curettage group (88.5% vs 65.0%, P=0.019). Adjuvant therapy-treated patients with stage I UPSC experienced significantly fewer recurrences than those receiving observation (P=0.003). Patients with advanced-stage UPSC who received combination therapy demonstrated a lower risk of local recurrence compared with those who received chemotherapy alone with a borderline significance (P=0.051). Elevated serum cancer antigen 125 level was associated with advanced-stage disease and recurrence (P<0.001). In multivariate analysis, tumor stage and optimal cytoreduction were independent predictors of survival. In substage analysis, complete surgical staging was associated with better overall survival (OS; yes vs no, HR: 0.05 [95% CI: 0.01–0.51], P=0.037) in patients with stage I UPSC. As for advanced stage, paclitaxel–platinum chemotherapy regimen and optimal cytoreduction were independent favorable prognostic factors for progression-free survival (paclitaxel–carboplatin [TC] vs other; HR =0.38, P=0.010; yes vs no, HR =0.45, P=0.032) and OS (TC vs other, HR =0.38, P=0.022; yes vs no, HR =0.54, P=0.013).ConclusionIn patients with stage I UPSC, complete staging was associated with better OS, and therefore, it should be performed in all patients. Tumor stage and optimal cytoreduction are the most significant prognostic factors. Recurrence can be improved in stage I patients treated with adjuvant therapy and in patients with advanced-stage disease treated with combined therapy. TC regimen may be the preferred regimen for chemotherapy.

Cancer Antigen 125 Levels are Significantly Associated With Prognostic Parameters in Uterine Papillary Serous Carcinoma.

Uterine papillary serous carcinoma (UPSC) is a highly aggressive subtype of endometrial carcinoma. Histopathologically, it resembles the pattern of serous papillary carcinoma of the ovary. Cancer antigen 125 (CA-125) is the most widely used biomarker in epithelial ovarian carcinoma. Its use in UPSC evaluation has yet to be determined. The purpose of this study was to investigate the significance of preoperative serum CA-125 as a prognostic factor in patients with UPSC. The study cohort included all women with UPSC operated in our institution between January 2002 and June 2016. All patients underwent complete surgical staging. Preoperative CA-125 was reviewed and correlated with clinical and pathological parameters. Sixty-one women met the study criteria. Median preoperative CA-125 was found to be significantly associated with disease stage. Patients with disease stages I to IV had median preoperative CA-125 levels of 12.15, 19.6, 22.6, and 177.5 U/mL (P < 0.0001) respectively. Levels of CA-125 were significantly associated with positive cytology (P < 0.0001), omental disease (P < 0.0001), pelvic or para-aortic lymph node metastasis (P < 0.0001), and adnexal involvement (P < 0.0001). The optimal cutoff that provided the best sensitivity and specificity for omental and parametrial involvement as well as positive cytology was 57.5 U/mL. For adnexal and lymph node involvement, the optimal cutoff value was 41.8 U/mL. In patients with UPSC, preoperative CA-125 level correlates with known prognostic parameters of endometrial carcinoma and is associated with extrauterine involvement. These data should stimulate the need for further evaluation of the role of CA-125 in predicting recurrence and survival in UPSC.

Isolated Splenic Parenchymal Recurrence in a Case of Carcinoma Ovary

Ovarian cancer has emerged as one of the most common malignancies in women in India. Majority of the ovarian cancers present at advanced stage, and, unfortunately, most of them are known to relapse after primary treatment. The pattern of recurrence is usually as disseminated disease. Although metastatic involvement of spleen is common in disseminated recurrences, isolated metastasis in spleen parenchyma is uncommon. We hereby report this rare case of isolated parenchymal splenic recurrence of epithelial ovarian cancer which developed 48 months after the initial treatment. The patient, a 40-year-old woman, with a preoperative diagnosis of Stage IIIB carcinoma ovary, underwent total abdominal hysterectomy bilateral salpingo-oophorectomy (TAH & BSO), omentectomy and pelvic lymph node sampling for a papillary serous carcinoma of the ovaries. She subsequently received six cycles of adjuvant chemotherapy. During follow-up, she was detected to have splenomegaly, along with rising levels of serum CA 125. CT scan revealed the 6 × 7 cm parenchymal splenic lesion. She was taken up for surgery and was detected to have isolated splenic mass. She underwent splenectomy. Histopathological evaluation revealed metastatic parenchymal disease consistent with recurrent ovarian cancer. She remains alive and disease free for 14 months since the last operation. Isolated parenchymal splenic lesions are very rare and may occur as a late recurrence in epithelial ovarian cancer. Splenectomy can be performed with acceptable morbidity and confers a substantial survival benefit to the patients.

Use of Aggressive Surveillance for Locoregional Endometrial Cancer After Local Therapy.

Current guidelines do not recommend routine surveillance imaging as part of follow-up care for patients treated for locoregional endometrial carcinoma. This study seeks to determine the potential benefit of routine surveillance imaging by evaluating outcomes of patients whose recurrences were detected on routine surveillance compared to those whose recurrences were identified after presenting with symptoms. We conducted a retrospective review of patients who developed recurrence after surgical treatment, with or without adjuvant therapy, for locoregional endometrial carcinoma. A total of 149 patients were identified with adequate clinical information regarding the recurrence. Cox proportional hazards regression analysis was used to estimate overall survival and progression-free survival. The median age of patients at diagnosis was 69.2 years (range, 38.0-99.5 years). Initial stages included stage I, 49.7%; stage II, 10.1%; stage III, 38.3%; and stage IV, 1.3%. Histologic diagnoses included endometrioid adenocarcinoma, 48.3%; and other diagnoses (including papillary serous carcinoma, clear cell carcinoma, and carcinosarcoma), 51.7%. Patients were initially treated with a variety of therapies: surgery alone in 20.8%, surgery and radiation in 25.5%, surgery and chemotherapy in 12.1%, and trimodality therapy in 41.6%. Sites of recurrence included 20.8% vaginal, 14.8% pelvic and 64.4% distant sites. Recurrences were detected asymptomatically in 86 patients (57.7%) and symptomatically in 63 patients (42.3%). Of those detected asymptomatically, 80.2% were detected by imaging. Overall, when comparing symptomatic versus asymptomatic recurrences, there was no difference in overall survival (hazard ratio, 1.24; 95% confidence interval, 0.84-1.83; P = 0.29) or progression-free survival (hazard ratio, 1.14; 95% confidence interval, 0.77-1.70; P = 0.52). Patients who develop asymptomatic recurrences of their endometrial carcinoma do not seem to have a better prognosis than those who present with symptomatic recurrences. Thus, these results do not support routine imaging surveillance for patients treated for locoregional endometrial carcinoma. Further prospective evaluation is needed.

Adjuvant paclitaxel and carboplatin chemotherapy interposed with radiotherapy in a “sandwich” protocol for uterine papillary serous carcinoma: a single institution experience and review of literature

Adjuvant paclitaxel and carboplatin chemotherapy interposed with radiotherapy in a “sandwich” protocol for uterine papillary serous carcinoma: a single institution experience and review of literature

Abstract 3130: Immune profiling in uterine papillary serous carcinoma cancer patients reveals distinct subpopulations and clinical outcomes

Abstract Uterine papillary serous carcinoma (UPSC) is a rare but aggressive type of endometrial cancer (EC) that represents 10% of cases of EC but accounts for 40% of EC deaths. Patients with UPSC have poor survival rates, a high risk of recurrence and frequently metastasize to the lymph nodes and the omentum. The mechanisms that drive UPSC progression have not been elucidated yet and immune profiling can be a valuable tool to understand the different patient outcomes. In this work, we used formalin fixed paraffin embedded (FFPE) tumor samples from a cohort of 140 patients with UPSC, the largest used to date, to study a panel of 7 immune markers by multiplex immunofluorescence, using the OpalTM system (Perkin Elmer) in the same tissue section. Samples were imaged with Vectra 3.0 multispectral microscope (Perkin Elmer) and images were analyzed using Visiopharm software. Tumor samples from primary, metastatic and recurrent sites were used to study the tumor microenvironment. We observed significant differences in the tumor-infiltrating immune cells between patients that recurred and those that did not. Similarly, immune subpopulations distinguished patients with metastasis compared to those with a less aggressive form of UPSC. Spatial distribution of cytotoxic T cells (CD8+ GranzymeB+) and cancer cells was also found to significantly correlate with overall patient survival. Collectively, our work shows the immune populations play a role in patient outcomes and should be taken into account for future therapeutic strategies. Citation Format: Angela Rynne Vidal, Karen H. Lu, Samuel C. Mok. Immune profiling in uterine papillary serous carcinoma cancer patients reveals distinct subpopulations and clinical outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3130.

Abstract LB-042: Successful tumor formation following xenotransplantation of primary human ovarian cancer cells into severe combined immunodeficient (SCID) pigs

Abstract Ovarian cancer (OvCa) is the most lethal gynecologic malignancy, with 2/3 of patients having late-stage disease (stages II-IV) at diagnosis. Preclinical animal models for cancer research have primarily been restricted to rodents, but many preclinical cancer drug trials that succeed in mice fail in humans, potentially due to vast differences in physiology and size. Therefore, we sought to determine if pigs, which are more similar to humans in terms of anatomy and physiology, would be a viable preclinical animal model for OvCa. Our group has pioneered the development of severe combined immunodeficiency (SCID) pigs for biomedical research, a key technological advancement for xenotransplantation of human ovarian cancer cells to form tumors. In this study, we injected human OSPC-ARK-1 cells, a chemotherapy-resistant primary ovarian serous papillary carcinoma cell line, into the neck muscle and ear tissue of four SCID and two non-SCID pigs. Tumors developed in the ears of three SCID pigs, while two SCID pigs developed tumors in neck tissue, all of which were confirmed at pathology as true neoplasms. Non-SCID animals did not develop tumors in any location. Confirmation that OSPC-ARK1 cells can form tumors in SCID pigs substantiates further development of orthotopic models of OvCa in pigs for researching improved OvCa therapeutic and diagnostic methods. Citation Format: Adeline N. Boettcher, Matti Kiupel, Malavika Adur, Emiliano Cocco, Alessandro Santin, Sara Charley, John Risinger, Christopher Tuggle, Erik Shapiro. Successful tumor formation following xenotransplantation of primary human ovarian cancer cells into severe combined immunodeficient (SCID) pigs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-042.

Association of thrombocytosis with disease specific survival in women with uterine papillary serous carcinoma.

e17561Background: Thrombocytosis has been reported to be associated with decreased survival in many cancers including uterine and ovarian cancer. The purpose of this study was to evaluate the assoc...