Ovarian Papillary Serous Carcinoma Research Articles

Pleural metastasis from ovarian papillary serous carcinoma form Coral Reef like formation- A unique presentation

Pleural metastasis from ovarian papillary serous carcinoma form Coral Reef like formation- A unique presentation

An unusual case of primary peritoneal adenocarcinoma

Primary peritoneal adenocarcinoma is sporadic with few cases cited in pre-existing literature. This cancer arises from the peritoneal epithelium lining of the abdomen, which is derived from extra ovarian mesothelium. It generally carries a poor prognosis. The treatment strategies are similar to ovarian serous papillary carcinoma. Report an incidental finding of primary peritoneal adenocarcinoma in a 39-year-old female army personnel, currently undergoing her chemotherapy and thriving. Exploratory laparotomy was done given the incidental finding of a mass on the contrast-enhanced computed tomography scan (CT). The mass was attached to the greater omentum, however, did not invade the mucosa of the transverse colon. Given this, part of greater omentum was removed. The findings of the immunohistochemical studies of the tumour are described within this report. The diagnosis of a primary peritoneal adenocarcinoma, stage II was established as no other primary site were found upon further investigation. The patient was treated with chemotherapy (carboplatin/paclitaxel) which was planned for 6 cycles. Otherwise, the patient had an uneventful postoperative course, is underway her chemotherapy regime and is planned for interim CT study to assess chemotherapy response. To conclude, isolated solitary primary peritoneal adenocarcinoma without peritoneal carcinomatosis, gastrointestinal manifestations and ascites are rare. This case, however, demonstrates the importance of its diagnosis, accurate evaluation and management.

Assessing and validating housekeeping genes in normal, cancerous, and polycystic human ovaries.

Housekeeping genes (HKGs), reference or endogenous control genes, are vital to normalize mRNA levels between different samples. Since using inappropriate HKGs can lead to unreliable results, selecting the proper ones is critical for gene expression studies. To this end, normal human ovaries, as well as those from patients diagnosed with ovarian endometrioid adenocarcinoma (OEA), ovarian mucinous adenocarcinoma (OMA), ovarian serous papillary carcinoma (OSPC), and polycystic ovary syndrome (PCOS), were used to identify the most suitable housekeeping genes. RNA was isolated from 5 normal human ovaries (52-79years of age), 9 cancerous ovaries (3 OEA, 3 OMA, 3 OSPC; 49-75years of age), and 4 PCOS ovaries (18-35years of age) in women undergoing hysterectomy. cDNA was synthesized using a whole transcriptome kit, and quantitative real-time PCR was performed using TaqMan array 96-well plates containing 32 human endogenous controls in triplicate. Among 32 HKGs studied, RPS17, RPL37A, PPIA, 18srRNA, B2M, RPLP0, RPLP30, HPRT1, POP4, CDKN1B, and ELF1 were selected as the best reference genes. This study confirms recent investigations demonstrating that conventional HKGs, such as GAPDH and beta-actin, are not suitable reference genes for specific pathological conditions, emphasizing the importance of determining the best HKGs on a case-by-case basis and according to tissue type. Our results have identified reliable HKGs for studies of normal human ovaries and those affected by OEA, OMA, OSPC, or PCOS, as well as combined studies of control subjects vs. each cancer or PCOS group.

Primary papillary serous carcinoma presenting as acute ovarian torsion in postmenopausal woman: a case report

A 51-year-old postmenopausal woman, with an uneventful past gynecologic history, was admitted to the present hospital with a diagnosis of severe pelvic pain due to a suspected ovarian torsion treated with different drugs intravenously without any improvement of symptoms. As a consequence of the increasing pelvic pain, a laparoscopic surgical treatment was decided: a left necrotic ovarian mass and pelvic peritoneal carcinomatosis were visualized and the procedure was converted from laparoscopy to laparotomy that confirmed a diagnosis of primary ovarian papillary serous carcinoma and permitted an adequate treatment. This is a rare case in literature of severe pelvic pain due to an acute ovarian torsion that permitted a prompt diagnosis and treatment of malignancy.

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.

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.

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.

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.

Abstract B079: Single agent AZD 1775, a Wee1 inhibitor, shows activity in BRCA deficient patients

Abstract Background: Modulation of BRCA1 and ATR has been postulated as an activation mechanism of checkpoint 1 (Chk1), which in turn triggers homologous recombination repair through modulation of BRCA2-Rad51, and the initiation of cell cycle checkpoints through phosphorylation and activation of Wee1. Wee1 is a tyrosine kinase implicated in the inhibitory phosphorylation of cyclin-dependent kinase 1 (CDK1/CDC2)-bound cyclin B, resulting in G2 cell cycle arrest in response to DNA damage. AZD1775 is a first-in-class selective inhibitor of Wee1 kinase that directly prevents phosphorylation of CDC2 at Tyr15. Model data show single-agent antitumor activity in multiple cancer cell lines across the NCI-60 and in both p53 intact and deficient tumor xenografts. We are conducting a phase I trial of AZD1775 in patients (pts) with refractory solid tumors, both with and without germline BRCA1/2 mutations (BRCA+), evaluating two different dosing schedules. We have previously reported on initial antitumor activity and proof-of-mechanism (Do et al, J Clin Oncol. 2015). This abstract reports the efficacy seen in the BRCA+ population. Methods: AZD1775 was administered orally twice daily (BID) for 5 doses [D1-3 and 8-10, Cohort A (A)] or once daily for 5 days [D1-5 and 8-12, Cohort B (B)] during weeks 1 and 2 of a 21-day cycle; 3+3 design. Primary objectives: establish safety, tolerability and PK of AZD1775. Secondary objectives: determine the effect of AZD1775 on markers of DNA damage and apoptosis in tumor tissue/circulating tumor cells, and antitumor activity. Dose-limiting toxicity (DLT) was determined during Cycle 1. Response defined by RECIST 1.1 on CT. Results: A total of 17 BRCA+ pts have enrolled; 9 pts on A (one pt withdrew for other therapy), and 8 pts on B. Nine pts with BRCA1, 7 pts with BRCA2: ovarian (9 pts), breast (2), pancreas (1), prostate (1), Fallopian tube (1), and peritoneal (1) cancer. Partial responses (PR) were confirmed on 2/8 pts (25%) in A with BRCA1 papillary serous ovarian cancer and squamous cell carcinoma of tongue. Two additional PRs (25%) were confirmed in BRCA1 serous ovarian cancer pts in B. Two further BRCA1 ovarian pts trended near PR. All 4 responders received prior platinum therapy; 3/3 ovarian cancer pts received and responded to prior PARP inhibitor therapy. No differences were noted in severity or rate of toxicity in pts with/without BRCA+: common grade 3/4 toxicities include anemia (6 pts, 37%), lymphopenia (5, 31%), neutropenia (4, 25%), and thrombocytopenia (3, 18%), occurring in responders and nonresponders. Conclusions: AZD1775 has single-agent antitumor activity in a BRCA deficient population, especially BRCA1. Responses were observed in pts with prior exposure to platinum and a PARP inhibitor. Additional accrual on a safety expansion cohort is ongoing, and assessment of PD biomarkers is planned for paired biopsies (NCT01748825). Citation Format: Geraldine OSullivan Coyne, Shivaani Kummar, Naoko Takebe, Khanh Tu Do, Robert Meehan, Richard Piekarz, Jennifer Zlott, Lamin Juwara, Mary Quinn, Elad Sharon, Howard Streicher, Lawrence Rubinstein, Chana Levine, James H. Doroshow, Alice P. Chen. Single agent AZD 1775, a Wee1 inhibitor, shows activity in BRCA deficient patients [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B079.

Outcomes and national practice patterns in management of ovarian carcinosarcoma compared with high-grade papillary serous ovarian carcinoma: An NCDB analysis of 76,369 patients

Outcomes and national practice patterns in management of ovarian carcinosarcoma compared with high-grade papillary serous ovarian carcinoma: An NCDB analysis of 76,369 patients

Ovarian Hormone Replacement Therapy in Gynecological Cancer Survivors

The number of survivors after gynecological cancer is increasing. In order to improve their quality of life, the need was felt to review the present status of ovarian steroid hormone replacement therapy (HRT) in them. The purpose was to examine the published literature on menopause management in them and highlight the risks and benefits. The literature search on menopause management in cancer survivors was performed. The research and review articles in English language on the subject that were available and accessible were reviewed. And the recommendations and opinions were presented as working guidelines. Treatment of some of gynecological cancers and the breast cancer results in abrupt loss of ovarian function and severe menopausal symptoms. Use of HRT in women with a genetic predisposition for or development of a gynecological malignancy suggests no proven adverse oncologic effects as a result of short-term use. The main concerns are the potential stimulation of residual cancer and the induction of new hormone-dependent disease. The majority of the most common gynecological malignancies like squamous cell carcinomas of the cervix, serous papillary epithelial ovarian carcinomas and squamous cell carcinomas of the vulva are not estrogen dependent. HRT is not shown to adversely affect the outcome in patients after treatment for hormone-sensitive cancers like early-stage endometrioid adenocarcinomas of the endometrium. In cases with low-grade endometrial stromal sarcomas, it is an absolute contraindication. The option needs to be discussed individually with the survivor providing unbiased information.

Patterns of care, predictors and outcomes of chemotherapy for ovarian carcinosarcoma: A National Cancer Database analysis

ObjectiveThe aim of this study is to determine if outcomes of patients with ovarian carcinosarcoma (OCS) differ from those of women with high-grade papillary serous ovarian carcinoma (HG-PSOC) when compared by stage and treatment modalities. MethodsThe National Cancer Database was queried to identify patients with OCS and HG-PSOC diagnosed between 2003 and 2011. Demographic and clinical data were compared, and the impact of tumor histology on survival was analyzed using the Kaplan–Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. ResultsThe final study group consisted of 45,153 women. 2886 (6.39%) had OCS and 42,267 (93.61%) had HG-PSOC. The mean age at diagnosis was 65.43 (±12.21) years for women with OCS and 61.52 (±12.6) years for HG-PSOC (P<0.001). African-American women had higher rate of OCS relative to white non-hispanic women (7.84% vs. 6.37%; P=0.002). Overall, women with OCS had a worse five-year survival rate, 26.63% [95% Confidence Interval (CI)=24.86%–28.53%] vs. 43.61% (95% CI=43.07%–44.17%). This difference persisted for each FIGO disease stage I–IV, with five-year survival consistently worse for women with OCS compared to those with HG-PSOC. Over the entire study period and after adjusting for histology, age, period of diagnosis, SEER registry, marital status, stage, surgery, radiotherapy, and lymph node dissection, carcinosarcoma histology was associated with decreased survival. ConclusionOCS is associated with a poor prognosis compared to HG-PSOC. This difference was noted across all FIGO stages.

A case report of primary psammomatous serous adenocarcinoma of the peritoneum

Extraovarian peritoneal serous papillary carcinoma is an uncommon malignant tumour characterised by peritoneal involvement with ascites, which is similar to ovarian serous papillary carcinoma histologically. Our case involved only the surface and superficial cortex of the ovaries, with peritoneal involvement, as described in the literature.

Cardiac Fibroelastoma versus Thrombus: Echocardiographic Evidence Can Be Misleading.

We present a case of a young female with stroke symptoms who underwent valve sparing resection of a presumed fibroelastoma based on echocardiographic findings. After confirming embolic stroke, she underwent excision of the lesion, which on pathology revealed a nonbacterial thrombus. Ultimately, this led to a more extensive work-up leading to the discovery of a papillary serous ovarian carcinoma, the underlying cause of her hypercoagulable state. The initial echocardiographic findings painted the clear picture of a papillary tumor on the aortic valve which was likely the source of the emboli resulting in ischemic stroke. This unique case presentation illustrates that imaging, including echocardiography, may not always coincide with the clinical diagnosis. Thus, understanding the differential diagnoses of cardiac masses is of vital clinical significance. The distinction of fibroelastoma versus the much less common finding of aortic thrombus may lead to early diagnosis of malignancy and prevention of life threatening events due to stroke or undiagnosed disease.

Carcinoma Seroso Papilar Peritoneal Primario: serie de casos Hospital Clínico Universidad de Chile 2010-2015

The primary peritoneal cancer is a low prevalence disease, within which primary papillary serous carcinoma of the peritoneum is the most frequent with an incidence of 6.78 cases per million inhabitants. Predominates in females and its main differential diagnosis is advanced ovarian papillary serous carcinoma, for which immunohistochemis­try and clinical and pathological classifications are the way to differentiate base on the World Health Organization classification for tumor lesions. Objective: Describe the immunohistochemical results of a series of cases studied in Universidad de Chile Clini­cal Hospital and to compare them with the literature. Material and Methods: Descriptive retrospective study based on analysis of biopsies from 12 cases between January 2010 and March 2015 classifying them according to age, sex and biopsy register. Routine histological te­chnique was performed in addition to the immunohistochemical staining for WT1, cytokeratin and other reagents according to the differential diagnoses. Results: The age distribution was 47 to 75 years, mean 60 years, 100% of cases female. Immunohistochemical reagents were predominant WT1 (53.8%) and cytokeratin-7 (38.5%). Conclusion: This carcinoma is a rare entity in routine clinical practice, with similarities to ovarian serous carci­noma. There is consensus on the diagnosis of this condition, which must be oriented according to the criteria of the Gynecologic Oncology Group. Clinical suspicion can lead the pathologist to perform immunohistochemical study and thus have an accurate diagnosis to determine the therapeutic approach of the surgeon.

Reacción de hipersensibilidad a carboplatino no reversible mediante protocolo de desensibilización

Platinum compounds are widely used in different tumors, being carboplatin indicated in ovarian carcinoma. The main carboplatin-dose limiting toxicity is the thrombocytopenia, however, sometimes we have seen hypersensitivity reactions that, although it is not a fact too often (8-16%), can be severe. For this reason, desensitization protocols have been developed.We report the case of a patient intervened surgically from a papillary serous carcinoma of ovary (stage IIIC) and who later received adjuvant chemotherapy with carboplatin and paclitaxel. After twenty-two months of disease-free interval, she showed unresectable abdominal relapse, so it was again treated with carboplatin and paclitaxel. During the administration of the second cycle, said severe hypersensitivity reaction to carboplatin.Attempted to desensitization unsuccessfully, can not continue with this treatment scheme and forcing to start second line with trabectedin and pegylated liposomal adriamycin.

Breast Metastasis of Serous Ovarian Papillary Carcinoma: A Report of Two Cases Diagnosed by Fine-Needle Aspiration

Breast metastases from gynecologic cancer are infrequent and are mainly from the ovary. They usually appear in advanced stages and have poor survival rates after diagnosis. Two cases of breast metastasis of serous ovarian carcinoma are presented. In both cases fine-needle aspiration (FNA) study of breast revealed a lesion with morphologic characteristics of serous carcinoma, while one of them was with immunocytochemical study. Origin was confirmed by histological examination of this lesion.

Serous Ovarian Carcinoma Recurring as Malignant Mixed Mullerian Tumor.

Only five cases of recurrence of malignant mixed Mullerian tumor (carcinosarcoma) from the ovarian carcinoma have been published in the literature to our knowledge. A 64-year-old woman first underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy because of pelvic mass. Histological diagnosis was serous papillary carcinoma of the left ovary. After six courses of chemotherapy, CA125 level returned to normal range. However, she had persistent multiple mediastinal and para-aortic lymphadenopathies in spite of additional six courses of chemotherapy. Then she underwent the second operation about 2 years after primary surgery. Multiple excisional biopsies were taken from subcutaneous tissue, over the bowels and the left external iliac artery. The histopathological diagnosis which was confirmed by immunohistochemical study was malignant mixed Mullerian tumor for all metastatic foci. A rare case of ovarian serous papillary carcinoma recurring as malignant mixed Mullerian tumor is reported.

Expression of miR-224-5p is associated with the original cisplatin resistance of ovarian papillary serous carcinoma.

Chemoresistance is a major challenge to successful chemotherapy of ovarian cancer, which represents the leading cause of mortality from gynecologic malignancies. We demonstrated that overexpression of miR-224-5p in ovarian cancer patients is associated with platinum-based chemoresistance using miRNA microarray analysis and quantitative real-time polymerase chain reaction (qRT-PCR) validation invivo, as well as in 4human ovarian cancer cell lines (C13/OV2008; A2780CP/A2780S) invitro. In the present study, we aimed to clarify the role of miR-224-5p in regulating the chemoresistance of ovarian cancer. By using the sensitive miRNA transient transfection, we demonstrated expression and bioactivity of miR-224-5p in ovarian cancer cell lines. It is of note that enforced expression of miR-224-5p enhanced chemoresistance to cisplatin in ovarian cancer cells through apoptosis reversion. We predicted and identified the PRKCD gene as one of the targets of miR-224-5p in mediating the primary chemoresistance of ovarian cancer patients. We showed reciprocal expression of miR-224-5p and PRKCD by quantitative analysis in complete response and incomplete response patients invivo, and 2 pairs of cisplatin resistance and sensitive cell lines invitro, after either miR-224-5p overexpression or knockdown transfection. Additionally, miR-224-5p and PRKCD can serve as novel predictors and prognostic biomarkers for ovarian papillary serous carcinoma (OPSC) patient response to overall disease-specific survival. Our findings suggest that miR-224-5p may function as an oncogene and induce platinum resistance in OPSC at least in part by downregulating PRKCD, thereby providing a biomarker for predicting chemosensitivity to cisplatin in patients with ovarian cancer.

The expression of miR-30a* and miR-30e* is associated with a dualistic model for grading ovarian papillary serious carcinoma

Histological grade has already been recognized as a very important prognostic factor for ovarian papillary serous carcinoma (OPSC). On the basis of pathogenetic mechanisms, recent findings suggest a dualistic model of OPSC consisting of typesI (low-grade) andII (high-grade) cancers. High-grade OPSC is responsible for most ovarian cancer deaths. The goal of our investigation was to identify the differences in key miRNAs and possible regulators through miRNA microarray chip analysis, as well as functional target prediction and clinical outcome between the low and high-grade OPSC patients. The pathogenic basis in differentiation of ovarian cancer subtypes was studied to provide insight into diagnosis and therapy for high-grade cases. Through microarray analysis, we found that miR-30a* and miR-30e* were the top 2 significantly different miRNAs between type I and type II OPSC patients, and both were remarkably downregulated in the latter type. ATF3 and MYC were indicated as potential co-targets of miR-30a* and miR-30e*, and showed a significant upregulation in typeII patients. As ATF3 and MYC are often associated with aggressive behavior and poor differentiation, especially in human cancers, these results are in good agreement with our findings and point toward a regulating differentiation function of the miR-30a* and miR-30e* genes. Further analysis using leave‑one-out cross predictions and Kaplan-Meier survival analysis strongly suggested that miR-30a* and miR-30e* can be used as biomarkers to tailor histological grade before starting the regimen, and they showed important roles in ovarian cancer differentiation resulting in poorer prognosis. In general, miR-30a* and miR-30e* coupled with expression data that reveal pathogenic regulation to predict histological differentiation, may operate to direct the formation of early detection and therapeutic approaches to individual OPSC patients, especially differentiation therapy to high-grade cases.