Kallikrein family proteases KLK6 and KLK7 are potential early detection and diagnostic biomarkers for serous and papillary serous ovarian cancer subtypes

Background

Early detection of ovarian cancer remains a challenge due to widespread metastases and a lack of biomarkers for early-stage disease. This study was conducted to identify relevant biomarkers for both laparoscopic and serum diagnostics in ovarian cancer.

Methods

Bioinformatics analysis and expression screening in ovarian cancer cell lines were employed. Selected biomarkers were further validated in bio-specimens of diverse cancer types and ovarian cancer subtypes. For non-invasive detection, biomarker proteins were evaluated in serum samples from ovarian cancer patients.

Results

Two kallikrein (KLK) serine protease family members (KLK6 and KLK7) were found to be significantly overexpressed relative to normal controls in most of the ovarian cancer cell lines examined. Overexpression of KLK6 and KLK7 mRNA was specific to ovarian cancer, in particular to serous and papillary serous subtypes. In situ hybridization and histopathology further confirmed significantly elevated levels of KLK6 and KLK7 mRNA and proteins in tissue epithelium and a lack of expression in neighboring stroma. Lastly, KLK6 and KLK7 protein levels were significantly elevated in serum samples from serous and papillary serous subtypes in the early stages of ovarian cancer, and therefore could potentially decrease the high “false negative” rates found in the same patients with the common ovarian cancer biomarkers human epididymis protein 4 (HE4) and cancer antigen 125 (CA-125).

Conclusion

KLK6 and KLK7 mRNA and protein overexpression is directly associated with early-stage ovarian tumors and can be measured in patient tissue and serum samples. Assays based on KLK6 and KLK7 expression may provide specific and sensitive information for early detection of ovarian cancer.

     

Comparison of stage III mucinous and serous ovarian cancer: a case-control study

Background

The purpose of this case-control study was to compare the prognoses of women with stage III mucinous ovarian carcinoma (MOC) who received maximal or optimal cytoreduction followed by paclitaxel plus carboplatin chemotherapy to those of women with stage III serous epithelial ovarian cancer (EOC) treated in the similar manner.

Methods

We performed a multicenter, retrospective review to identify patients with stage III MOC at seven gynecologic oncology departments in Turkey. Eighty-one women with MOC were included. Each case was matched to two women with stage III serous EOC in terms of age, tumor grade, substage of disease, and extent of residual disease. Survival estimates were measured using Kaplan-Meier plots. Variables predictive of outcome were analyzed using Cox regression models.

Results

With a median follow-up of 54 months, the median progression-free survival (PFS) for women with stage III MOC was 18.0 months (95% CI; 13.8–22.1, SE: 2.13) compared to 29.0 months (95% CI; 24.04–33.95, SE: 2.52) in the serous group (p?=?0.19). The 5-year overall survival rate of the MOC group was significantly lower than that of the serous EOC group (44.9% vs. 66.3%, respectively; p?<?0.001). For the entire cohort, presence of multiple peritoneal implants (Hazard ratio [HR] 2.39; 95% confidence interval [CI], 1.38–4.14, p?=?0.002) and mucinous histology (HR 2.28; 95% CI, 1.53–3.40, p?<?0.001) were identified as independent predictors of decreased OS.

Conclusion

Patients with MOC seem to be 2.3 times more likely to die of their tumors when compared to women with serous EOC.

     

Prognostic analysis for Chinese patients with stage I ovarian endometrioid carcinoma

Background

This study aimed to identify the clinical and pathological characteristics and the possible prognostic factors for Chinese patients with early-stage ovarian endometrioid carcinoma.

Methods

The present study reviewed the medical records of patients who received initial treatment and a postoperative pathological diagnosis of ovarian endometrioid carcinoma at our center. In all, 78 patients had stage I ovarian endometrioid carcinoma.

Results

In this series, the 5-year overall survival rate and 5-year disease-free survival (DFS) rates of patients with stage I ovarian endometrioid carcinoma was 98.7% and 87.2%, respectively. Univariate analysis showed the factors that influence the DFS rates include menopausal status, FIGO stage, histological grade, lymphadenectomy, cytology of ascites. Multivariate analysis showed that grade 3 and lymphadenectomy were the independent prognostic factors of DFS for Stage I ovarian endometrioid carcinoma (P = 0.0259, 0.0276 respectively). However, the coexisting endometriosis, concomitant endometrial disorders, dissection of para-aortic lymph node and more courses of thermotherapy had no influence on DFS. Besides, it was found that 19.3% of patients in this series had synchronous early stage and well-to-moderate differentiated endometrial carcinoma.

Conclusions

Grade 3 and lymphadenectomy were indicated as the independent factors of DFS for stage I patients with ovarian endometrioid carcinoma. The endometrial changes should be considered seriously when fertility-sparing surgery was planned.

     

Serous Tubal Carcinogenesis: The Recent Concept of Origin of Ovarian,Primary Peritoneal and Fallopian Tube High-Grade Serous Carcinoma

Background

Pelvic (non-uterine) high-grade serous carcinomas (PHGSC) including ovarian, tubal and primary peritoneal serous carcinomas have increased death: incidence ratio due to presentation at advanced stage, rapid progression, poor prognosis and high morbidity. Ambiguity regarding their pathogenesis and lack of a proper screening method is the cause of their late detection and high fatality rate. This study was undertaken to assess the fallopian tube for the presence of precursor lesions in pelvic serous carcinoma.

Methods

This was a prospective case–control study carried out in a tertiary care center. Consecutive specimens of 55 cases of pelvic high-grade serous carcinoma and 41 controls inclusive of 21 low-grade serous carcinoma, 10 benign adnexal masses and 10 normal adnexa were included in the study. Both side fallopian tubes in each case were subjected to histopathological examination and p53, Ki67 immunohistochemistry.

Results

There were 55 cases of PHGSC comprising of 50 cases of ovarian HGSC, two cases of primary peritoneal carcinoma (PPC) and three cases of tubal carcinoma. Serous tubal intraepithelial carcinoma (STIC) was detected in 14 cases (28%), p53 signature in 13 cases (26%) and tubal intraepithelial lesion in transition in 10 cases (20%) of ovarian HGSC. One case (50%) of PPC and one (33%) case of tubal carcinoma revealed the presence of STIC. None of the controls exhibited any precursor lesion except ovarian low-grade serous carcinoma where p53 was detected in 20% of cases.

Conclusion

This revelation concludes that fallopian tubes are the sites of precursors of PHGSC to a large extent. In the absence of a proper screening method of HGSC, prophylactic bilateral salpingectomy at hysterectomy for benign diseases can achieve ultimate goal of reduction in incidence of PHGSC.

     

Increased androgen receptor expression in serous carcinoma of the ovary is associated with an improved survival

Background

Altered androgen hormone homeostasis and androgen receptor (AR) activity have been implicated in ovarian carcinogenesis but the relationship between AR expression in ovarian cancer and clinical outcome remains unclear.

Methods

In this study, the prognostic impact of AR expression was investigated using immunohistochemistry in tissue microarrays from 154 incident cases of epithelial ovarian cancer (EOC) in the prospective, population-based cohorts Malmö Diet and Cancer Study and Malmö Preventive Project. A subset of corresponding fallopian tubes (n = 36) with no histopathological evidence of disease was also analysed.

Results

While abundantly expressed in the majority of fallopian tubes with more than 75% positive nuclei in 16/36 (44%) cases, AR was absent in 108/154 (70%) of EOC cases. AR expression was not related to prognosis in the entire cohort, but in the serous subtype (n = 90), AR positivity (> 10% positive nuclei) was associated with a prolonged disease specific survival in univariate (HR= 0.49; 95% CI 0.25-0.96; p= 0.038) and multivariate (HR= 0.46; 95% CI 0.22-0.97; p= 0.042) analysis, adjusted for age, grade and clinical stage.

Conclusions

AR expression is considerably reduced in EOC as compared to fallopian tubes, and in EOC of the serous subtype, high AR expression is a favourable prognostic factor. These results indicate that assessment of AR expression might be of value for treatment stratification of EOC patients with serous ovarian carcinoma.

     

Contemporary Treatment Strategies for Rare Epithelial Ovarian Cancers

Purpose of Review

Epithelial ovarian carcinoma consists of not one but five distinct histologic subtypes which include high-grade and low-grade serous carcinomas, clear cell, endometrioid, and mucinous carcinoma. Until recently, women with all histologic subtypes have been “grouped together” in cooperative group trials and treated in a similar fashion.

Recent Findings

Recent advances have demonstrated that each subtype differs in molecular and genetic differentiation, pathogenesis, clinical behavior, and response to treatments. Since the establishment of the Gynecologic Oncology Group (GOG) Rare Tumor Committee in 2005, there has been increasing emphasis placed upon novel treatment strategies for these low incidence malignancies. There has been mounting evidence to suggest that a “one-size-fits-all” treatment approach is not appropriate—especially for low-grade serous, clear cell, endometrioid, and mucinous carcinomas as they all tend to be relatively chemoresistant to typical platinum/taxane-based chemotherapy regimens utilized for high-grade serous carcinomas.

Summary

We present a review of the rare epithelial ovarian cancer subtypes, including current best clinical practices for the management of each tumor type.

     

Fractionated Palliative Pelvic Radiotherapy as an Effective Modality in the Management of Recurrent/Refractory Epithelial Ovarian Cancers: An Institutional Experience

Background

The advent of effective chemotherapeutic agents for ovarian carcinoma has made radical abdomino-pelvic radiation redundant. Nevertheless, palliative pelvic radiotherapy still has a role in palliating local symptoms. However, its effect on progression-free survival (PFS) may be debated.

Aims

To study the outcome of fractionated palliative pelvic radiotherapy in relapsed ovarian cancers in terms of symptom control and PFS.

Methods

Twenty-three patients of ovarian cancers, heavily pretreated with chemotherapy and with recurrent or residual pelvic masses, were planned for palliative pelvic radiotherapy to the dose of 46–50 Gy in 23–25 fractions in 4.5–5 weeks. Symptom control and outcomes have been analyzed.

Results

Post-radiotherapy, abdominal pain was controlled in 15 out of 17 patients (88.2 %), bleeding per vaginum in all 5 patients and vaginal discharge stopped in 4 out of 5 patients (80 %). On follow-up, of 23 patients, 17 (74 %) had progressive disease post-radiation, and median time to disease progression was 10 months (range 1–49). On univariate analysis, increased PFS was observed in patients who received radiation late in their course of disease, those with serous histology, and with lesser disease bulk in pelvis (≤2 cm) prior to radiation initiation.

Conclusion

Fractionated palliative pelvic radiotherapy is an efficient method for symptom palliation in relapsed ovarian cancers. Patients who are heavily pretreated with chemotherapy and have a small-volume pelvic disease may show a prolonged PFS with addition of pelvic radiotherapy. Indications of radiotherapy, however, need to be defined.

     

The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells

Objective

Previously, it has been shown that KIF14 mRNA is overexpressed in ovarian cancer (OvCa), regardless of histological subtype. KIF14 levels are independently predictive of poor outcome and increased rates of recurrence in serous OvCa patients. Furthermore, it has been shown that KIF14 also controls the in vivo tumorigenicity of OvCa cell lines. In this study, we evaluate the potential of KIF14 as a therapeutic target through selective inhibition of KIF14 in primary high-grade serous patient-derived OvCa cells.

Methods

To assess the dependence of primary serous OvCa cultures on KIF14, protein levels in 11 prospective high grade serous ovarian cancer samples were increased (KIF14 overexpression by transfection) or decreased (anti-KIF14 shRNA) in vitro, and proliferative capacity, anchorage independence and xenograft growth were assessed.

Results

Seven of eleven samples demonstrated increased/decreased in vitro proliferation in response to KIF14 overexpression/knockdown, respectively. When examining in vitro tumorigenicity (colony formation) and in vivo growth (subcutaneous xenografts) in response to KIF14 manipulation, none of the samples demonstrated growth in soft agar (11 samples), or xenograft growth (4 samples).

Conclusions

Although primary high-grade serous OvCa cells may depend on KIF14 for in vitro proliferation we were unable to demonstrate a role for KIF14 on tumorigenicity or develop an in vivo model for assessment. We have, however developed an effective in vitro method to evaluate the effect of target gene manipulation on the proliferative capacity of primary OvCa cultures.

     

Evaluation of primary adnexal masses by 3T MRI: categorization with conventional MR imaging and diffusion-weighted imaging

Background

To investigate the 3.0-Tesla (3 T) magnetic resonance imaging (MRI) characteristics of primary adnexal lesions for discriminating benign from malignant lesions.

Methods

One hundred thirty-nine patients with pathologically proven primary adnexal masses referred for 3 T MRI assessment preoperatively were included. Baseline characteristics, components, and conventional MRI and diffusion-weighted imaging (DWI-MRI) signals were recorded and compared.

Results

There were 22 ovarian cysts, 33 endometriomas, 43 benign tumors and 42 malignant tumors. When ovarian cyst and endometrioma were excluded, there were no significant differences in patients’ age between benign and malignant tumor (P = 0.235). There were no significant differences (P = 0.606) in the conventional MRI signals and significant difference (P = 0.008) in DWI-MRI signal between the non-malignant and malignant lesions. There was a significant difference (P = 0.000) in the apparent diffusion coefficient values (ADCs) between the non-malignant and malignant lesions.

Conclusions

3 T MRI categorized the characteristics of primary adnexal lesions. Conventional MRI signals were not useful for characterizing between benign and malignant lesions. DWI-MRI and ADCs were helpful for distinguishing malignant from benign ovarian lesions.

     

RETRACTED ARTICLE: Investigation of the hub genes and related mechanism in ovarian cancer via bioinformatics analysis

Background

Ovarian cancer is a cancerous growth arising from the ovary.

Objective

This study was aimed to explore the molecular mechanism of the development and progression of the ovarian cancer.

Methods

We first identified the differentially expressed genes (DEGs) between the ovarian cancer samples and the healthy controls by analyzing the GSE14407 affymetrix microarray data, and then the functional enrichments of the DEGs were investigated. Furthermore, we constructed the protein-protein interaction network of the DEGs using the STRING online tools to find the genes which might play important roles in the progression of ovarian cancer. In addition, we performed the enrichment analysis to the PPI network.

Results

Our study screened 659 DEGs, including 77 up- and 582 down-regulated genes. These DEGs were enriched in pathways such as Cell cycle, p53 signaling pathway, Pathways in cancer and Drug metabolism. CCNE1, CCNB2 and CYP3A5 were the significant genes identified from these pathways. Protein-protein interaction (PPI) network was constructed and network Module A was found closely associated with ovarian cancer. Hub nodes such as VEGFA, CALM1, BIRC5 and POLD1 were found in the PPI network. Module A was related to biological processes such as mitotic cell cycle, cell cycle, nuclear division, and pathways namely Cell cycle, Oocyte meiosis and p53 signaling pathway.

Conclusions

It indicated that ovarian cancer was closely associated to the dysregulation of p53 signaling pathway, drug metabolism, tyrosine metabolism and cell cycle. Besides, we also predicted genes such as CCNE1, CCNB2, CYP3A5 and VEGFA might be target genes for diagnosing the ovarian cancer.

     

Ovarian mucinous adenocarcinoma with functioning stroma in postmenopausal women: aromatase and SF-1 expressions

Background

A high serum estradiol (E2) level is occasionally detected in postmenopausal women with common epithelial ovarian tumors with functioning stroma. It has been proven that functioning stroma has the capacity to convert androgens to estrogens. However, the mechanism of the initiation and development of functioning stroma remains unclear.

Case Presentation

We present two cases of elevated E2 levels in elderly women with ovarian mucinous adenocarcinomas that contained functioning stroma. Immunohistochemical evaluation revealed high expression levels of aromatase and steroidogenic factor-1 (SF-1), which is considered to be a master regulator of steroidogenesis, in their ovarian stroma.

Conclusions

These cases suggest that overexpression of SF-1 may promote estrogen biosynthesis through regulation of P450 aromatase expression in ovarian tumors with functioning stroma; this in turn induces high serum E2 levels in postmenopausal women with common epithelial ovarian tumors.

     

Development of a syngeneic mouse model of epithelial ovarian cancer

Background

Most cases of ovarian cancer are epithelial in origin and diagnosed at advanced stage when the cancer is widely disseminated in the peritoneal cavity. The objective of this study was to establish an immunocompetent syngeneic mouse model of disseminated epithelial ovarian cancer (EOC) to facilitate laboratory-based studies of ovarian tumor biology and preclinical therapeutic strategies.

Methods

Individual lines of TgMISIIR-TAg transgenic mice were phenotypically characterized and backcrossed to inbred C57BL/6 mice. In addition to a previously described line of EOC-prone mice, two lines (TgMISIIR-TAg-Low) were isolated that express the oncogenic transgene, but have little or no susceptibility to tumor development. Independent murine ovarian carcinoma (MOVCAR) cell lines were established from the ascites of tumor-bearing C57BL/6 TgMISIIR-TAg transgenic mice, characterized and tested for engraftment in the following recipient mice: 1) severe immunocompromised immunodeficient (SCID), 2) wild type C57BL/6, 3) oophorectomized tumor-prone C57BL/6 TgMISIIR-TAg transgenic and 4) non-tumor prone C57BL/6 TgMISIIR-TAg-Low transgenic. Lastly, MOVCAR cells transduced with a luciferase reporter were implanted in TgMISIIR-TAg-Low mice and in vivo tumor growth monitored by non-invasive optical imaging.

Results

Engraftment of MOVCAR cells by i.p. injection resulted in the development of disseminated peritoneal carcinomatosis in SCID, but not wild type C57BL/6 mice. Oophorectomized tumor-prone TgMISIIR-TAg mice developed peritoneal carcinomas with high frequency, rendering them unsuitable as allograft recipients. Orthotopic or pseudo-orthotopic implantation of MOVCAR cells in TgMISIIR-TAg-Low mice resulted in the development of disseminated peritoneal tumors, frequently accompanied by the production of malignant ascites. Tumors arising in the engrafted mice bore histopathological resemblance to human high-grade serous EOC and exhibited a similar pattern of peritoneal disease spread.

Conclusions

A syngeneic mouse model of human EOC was created by pseudo-orthotopic and orthotopic implantation of MOVCAR cells in a susceptible inbred transgenic host. This immunocompetent syngeneic mouse model presents a flexible system that can be used to study the consequences of altered gene expression (e.g., by ectopic expression or RNA interference strategies) in an established MOVCAR tumor cell line within the ovarian tumor microenvironment and for the development and analysis of preclinical therapeutic agents including EOC vaccines and immunotherapeutic agents.

     

Prognostic value of MMP-2 for patients with ovarian epithelial carcinoma: a systematic review and meta-analysis

Background

The reported roles of matrix metalloproteinase 2 (MMP-2) on the prognosis of patients with epithelial ovarian cancers (EOCs) are inconsistent.

Objective

This meta-analysis was performed to evaluate the prognostic significance of MMP-2 for patients with EOCs by analyzing 11 studies.

Methods

We systematically searched articles in the Cochrane Library, Pubmed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Biological Medical (CBM) Database, updated to February 1^st 2015, with the following search terms: ovarian neoplasm OR ovarian tumor OR ovarian carcinoma OR ovarian malignance OR ovarian cancer AND matrix metalloproteinase-2 OR MMP-2.

Results

A total of 11 studies involving 1058 patients with EOCs were in accordance with the inclusion criteria. The pooled HR was 1.09 (95% CI 0.32–1.86, p = 0.006) in patients with overexpression of stromal MMP-2 with significant heterogeneity (I ² = 53.1%, p = 0.074) between studies. For patients with MMP-2 overexpression in tumor cells, the pooled HR was 1.42 (95% CI 1.14–1.70, p = 0.000) with no significant heterogeneity (I ² = 43.4%, p = 0.078) between studies. Sensitivity analyses were stable.

Conclusions

MMP-2 overexpression in tumor cells rather than stroma was significantly associated with poor prognosis in patient with endothelial ovarian cancer; however, the result remains to be confirmed with additional high-quality studies.

     

Does preoperative neutrophil to lymphocyte or platelet to lymphocyte ratios have a role in predicting borderline ovarian tumors?

Background

to investigate the value of using preoperative neutrophil to lymphocyte and platelet to lymphocyte levels in the patients of borderline ovarian tumors.

Methods

During the period between January 2002 and December 2015, the pathology reports and archival files of the Gynecologic Oncology Department of Çukurova University Medical Hospital and the Gynecologic Oncology Department of Dumlup?nar University, Evliya Çelebi Education and Research Hospital were retrospectively reviewed, and 144 patients of borderline ovarian tumor (as the study group) and 123 patients of serous cystadenoma (as the control group) were determined for eligibility in this study. Data regarding age, menopausal status, preoperative ultrasound findings, ca125 and complete blood counts were reviewed. Neutrophil to lymphocyte and platelet to lymphocyte ratios were calculated and these parameters were statistically compared between the groups.

Results

There was a statistically significant difference between the groups according to neutrophil count, platelet count, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio; in addition to age, ca125 and preoperative ultrasound findings.

Conclusions

It seems that neutrophil to lymphocyte and platelet to lymphocyte ratios are useful in predicting borderline ovarian tumors, preoperatively. However, further prospective studies are needed.

     

Targeting of mesenchymal stem cells to ovarian tumors via an artificial receptor

Background

Mesenchymal Progenitor/Stem Cells (MSC) respond to homing cues providing an important mechanism to deliver therapeutics to sites of injury and tumors. This property has been confirmed by many investigators, however, the efficiency of tumor homing needs to be improved for effective therapeutic delivery. We investigated the feasibility of enhancing MSC tumor targeting by expressing an artificial tumor-binding receptor on the MSC surface.

Methods

Human MSC expressing an artificial receptor that binds to erbB2, a tumor cell marker, were obtained by transduction with genetically modified adenoviral vectors encoding an artificial receptor (MSC-AR). MSC-AR properties were tested in vitro in cell binding assays and in vivo using two model systems: transient transgenic mice that express human erbB2 in the lungs and ovarian xenograft tumor model. The levels of luciferase-labeled MSCs in erbB2-expressing targeted sites were evaluated by measuring luciferase activity using luciferase assay and imaging.

Results

The expression of AR enhanced binding of MSC-AR to erbB2-expressing cells in vitro, compared to unmodified MSCs. Furthermore, we have tested the properties of erbB2-targeted MSCs in vivo and demonstrated an increased retention of MSC-AR in lungs expressing erbB2. We have also confirmed increased numbers of erbB2-targeted MSCs in ovarian tumors, compared to unmodified MSC. The kinetic of tumor targeting by ip injected MSC was also investigated.

Conclusion

These data demonstrate that targeting abilities of MSCs can be enhanced via introduction of artificial receptors. The application of this strategy for tumor cell-based delivery could increase a number of cell carriers in tumors and enhance efficacy of cell-based therapy.

     

High-grade serous ovarian cancer: the clone wars

Background

The last 5 years’ studies using next-generation sequencing provided evidences that many types of solid tumors present spatial and temporal genetic heterogeneity and are composed of multiple populations of genetically distinct subclones that evolve over time following a pattern of branched evolution. The evolutionary nature of cancer has been proposed as the major contributor to drug resistance and treatment failure. In this review, we present the current state of knowledge about the clonal evolution of high-grade serous ovarian cancer and discuss the challenge that clonal evolution poses for efforts to achieve an optimal cancer control.

Methods

A systemic search of peer-reviewed articles published between August 2007 and October 2016 was performed using PUBMED and Google Scholar database.

Results and conclusions

Recent studies using next-generation sequencing have allowed us to look inside the evolutionary nature of high-grade serous ovarian cancer, which in the light of current evidence can explain the relapsing course of the disease frequently observed in the clinical practice. Since only minimal improvement in the survival of patients treated with standard therapy has been observed in the last decade, novel molecular targeted therapies are of great interest in high-grade serous ovarian cancer. However, both spatial and temporal intratumoral genetic heterogeneity is a major challenge for personalized medicine, and greater knowledge of the molecular rules that drive tumor evolution through space and time is required to achieve a long-term clinical benefit from personalized therapy.

     

Synuclein-γ (SNCG) expression in ovarian cancer is associated with high-risk clinicopathologic disease

Background

Synuclein gamma (SNCG) expression is associated with advanced disease and chemoresistance in multiple solid tumors. Our goal was to determine if SNCG protein expression in ovarian cancer was correlated with clinicopathologic variables and patient outcomes.

Methods

Tissue microarrays from primary tumors of 357 ovarian, fallopian tube, and primary peritoneal cancer patients, who underwent primary surgery at Roswell Park Cancer Institute between 1995 and 2007, were immunohistochemically stained for SNCG. A pathologist blinded to patient data scored tumors as positive if ≥10 % of the sample stained for SNCG. Medical records were reviewed for clinicopathologic and demographic variables. Between the positive and negative groups, Wilcoxon rank-sum test was used to compare the median ages and Fisher’s exact test was used to compare groups in categorical variables. Cox proportional hazard models examined associations between SNCG and overall and progression-free survival.

Results

The median follow-up was 36 months, median overall survival was 39 months, and median progression-free survival was 18 months. SNCG presence was associated with clinical variables of serous histology, grade 3 disease, suboptimal debulking, ascites at surgery, FIGO stage III-IV cancer, or initial CA-125 level >485. There was no significant difference in overall survival (HR 1.06 95 % CI 0.81–1.39 P 0.69) or progression-free survival (HR 1.16 95 % CI 0.89–1.50 P 0.28) for patients with or without SNCG expression.

Conclusions

SNCG expression in ovarian cancer is frequent in patients with high-risk features, but it does not correlate with chemotherapy response, overall survival, or progression-free survival.

     

Preoperative elevated platelet count and thrombocytosis in gynecologic malignancies

Purpose

Platelets have multiple functions and they also play an important role in malignancies. Elevated platelet count and thrombocytosis at the time of diagnosis in patients with many solid tumors correlates with prognosis and is associated with poor survival. The aim of the following report is to review the literature concerning elevated platelet count and thrombocytosis in gynecologic malignancies.

Method

A PubMed search of all English literature peer-reviewed publications was performed containing the terms elevated platelet count or thrombocytosis and vulvar cancer, cervical cancer, endometrial cancer, and ovarian cancer. All studies published until December 31, 2015, were included in the following review.

Results

A pretreatment elevated platelet count and thrombocytosis have been shown to be associated with a poor prognosis in many studies of gynecologic malignancies with the exception of vulvar carcinoma.

Conclusion

Since elevated platelet count and thrombocytosis may be prevented by blocking thrombopoietic cytokines, their assessment may, in the future, be of therapeutic significance.