H-Ferritin Affects Cisplatin-Induced Cytotoxicity in Ovarian Cancer Cells through the Modulation of ROS.

Reactive oxygen species (ROS) mediates cisplatin-induced cytotoxicity in tumor cells. However, when cisplatin-induced ROS do not reach cytotoxic levels, cancer cells may develop chemoresistance. This phenomenon can be attributed to the inherited high expression of antioxidant protein network. H-Ferritin is an important member of the antioxidant system due to its ability to store iron in a nontoxic form. Altered expression of H-Ferritin has been described in ovarian cancers; however, its functional role in cisplatin-based chemoresistance of this cancer type has never been explored. Here, we investigated whether the modulation of H-Ferritin might affect cisplatin-induced cytotoxicity in ovarian cancer cells. First, we characterized OVCAR3 and OVCAR8 cells for their relative ROS and H-Ferritin baseline amounts. OVCAR3 exhibited lower ROS levels compared to OVCAR8 and greater expression of H-Ferritin. In addition, OVCAR3 showed pronounced growth potential and survival accompanied by the strong activation of pERK/pAKT and overexpression of c-Myc and cyclin E1. When exposed to different concentrations of cisplatin, OVCAR3 were less sensitive than OVCAR8. At the lowest concentration of cisplatin (6 µM), OVCAR8 underwent a consistent apoptosis along with a downregulation of H-Ferritin and a consistent increase of ROS levels; on the other hand, OVCAR3 cells were totally unresponsive, H-Ferritin was almost unaffected, and ROS amounts met a slight increase. Thus, we assessed whether the modulation of H-Ferritin levels was able to affect the cisplatin-mediated cytotoxicity in both the cell lines. H-Ferritin knockdown strengthened cisplatin-mediated ROS increase and significantly restored sensitivity to 6 µM cisplatin in resistant OVCAR3 cells. Conversely, forced overexpression of H-Ferritin significantly suppressed the cisplatin-mediated elevation of intracellular ROS subsequently leading to a reduced responsiveness in OVCAR8 cells. Overall, our findings suggest that H-Ferritin might be a key protein in cisplatin-based chemoresistance and that its inhibition may represent a potential approach for enhancing cisplatin sensitivity of resistant ovarian cancer cells.

MicroRNA let-7g acts as tumor suppressor and predictive biomarker for chemoresistance in human epithelial ovarian cancer.

Remarkable deregulation of microRNAs has been demonstrated in epithelial ovarian cancer (EOC). In particular, some of the let-7 miRNA family members have been proposed as tumor suppressors. Here, we explored the functional roles of let-7g in EOC. The ectopic overexpression of let-7g in OVCAR3 and HEY-A8 EOC cells induced i) a down-regulation of c-Myc and cyclin-D2 thus promoting cell cycle arrest, ii) a reduction of Vimentin, Snail and Slug thus counteracting the progression of epithelial to mesenchymal transition, iii) a chemosensitization to cis-platinum treatment. Next, analysis of human EOC tissues revealed that let-7g expression was significantly reduced in tumor tissue specimens of patients with EOC compared to their non-tumor counterparts (p = 0.0002). Notably, low let-7g tissue levels were significantly associated with acquired chemoresistance of patients with late-stage of EOC (n = 17, p = 0.03194). This finding was further validated in the serum samples collected from the same cohort of patients (n = 17, p = 0.003). To conclude, we demonstrate that let-7g acts as tumor suppressor and might be used to disable EOC tumor progression and chemoresistance to cis-platinum-based chemotherapy. Furthermore, we propose that decreased expression of let-7g could serve as a tissue and serum biomarker able to predict the chemo-resistant features of EOC patients.

A more accurate method to interpret lactate dehydrogenase (LDH) isoenzymes' results in patients with uterine masses.

OBJECTIVE: Since there are no approved reliable biomarkers for detecting preoperatively uterine sarcoma, lactate dehydrogenase (LDH) isoenzymes are usually required. We first evaluated the role of LDH isoenzymes in detecting uterine sarcoma risk, and then we tried to introduce a model to easily interpret the biochemical results. METHODS: We retrospectively retrieved records of patients who underwent surgical treatment for uterine masses from 2004 to 2016, and we compared data of 2211 patients with a definitive surgical diagnosis of uterine fibroids and 43 with uterine sarcomas. Quantitative relationships between serum LDH isoenzymes levels, as different single markers or in multiple assays, and the final diagnosis were investigated. RESULTS: LDH isoenzymes levels significantly differed between patients with benign uterine masses or sarcomas. LDH3 isoenzyme exhibited better predictive performances than the other four isoforms. Combining LDH3 with LDH1 isoenzymes into an inverse algebraic relationship, named Uterine mass Magna Graecia (U.M.G.) risk index, the accuracy of markers in discriminating between benign and suspicious malignant uterine masses was significantly enhanced, sensitivity at 100% and specificity at 99.6%, with nine false positive over 2211 benignant cases and no false negative over 43 sarcomas. CONCLUSIONS: This retrospective analysis suggests to consider U.M.G. risk index as an inexpensive and accurate prognostic index that, once validated in a prospective study, may help clinicians in discriminating between benignant and suspicious malignant uterine masses.

Subcutaneous Progesterone for Endometrial Polyps in Premenopausal Women: A Preliminary Retrospective Analysis.

STUDY OBJECTIVE: To investigate the effects of 3 cycles of subcutaneous progesterone administered during the luteal phase on the regression rate of symptomatic and asymptomatic endometrial polyps in premenopausal woman. DESIGN: A retrospective study (Canadian Task Force classification II-2). SETTING: A department of obstetrics and gynecology in a university hospital. PATIENTS: One hundred twenty-seven reproductive-aged women presented with endometrial polyps from January to December 2016. INTERVENTIONS: A retrospective comparison of patients treated with subcutaneous progesterone and those managed by the "wait and see" approach. MEASUREMENTS AND MAIN RESULTS: Patients were divided into 2 groups: the group treated with subcutaneous progesterone (cases) and the wait and see group (controls). Women in the treatment group were administered 25 mg subcutaneous progesterone during the luteal phase for 7 days for 3 months. The wait and see group included patients refusing progesterone therapy who were reevaluated 3 menstrual cycles after the transvaginal sonographic diagnosis. Both the treatment group (n = 61) and the wait and see group (n = 32) were evaluated with a follow-up ultrasound examination after 3 months. The regression rate of endometrial polyps in women treated with subcutaneous progesterone was compared with the wait and see patients. The regression in the number and/or dimensions of the polyps was greater in the treatment group than the control group. The regression rate was 47.5% and 12.5%, respectively (p < .001). CONCLUSION: Progesterone appears to be a valid therapeutic alternative for the management of endometrial polyps. A prospective, randomized study is ongoing at our institution to further validate these findings.

Increased LDH5/LDH1 ratio in preoperative diagnosis of uterine sarcoma with inconclusive MRI and LDH total activity but suggestive CT scan: a case report.

BACKGROUND: Morcellation of undiagnosed uterine sarcoma is cause of abdominal/pelvic dissemination, residual tumor and recurrence. In the preoperative evaluation of suspect uterine masses, magnetic resonance imaging (MRI) and serum lactate dehydrogenase (LDH) total activity are referred to as the most effective tools, while computed tomography scan (CT) and LDH isoenzymes are less considered in literature. CASE PRESENTATION: A 46 year old woman was admitted to our department with a large uterine mass. Ultrasonography, MRI and LDH total activity did not allow a diagnosis of malignancy, and the woman expressed the wish to avoid hysterectomy. In spite of this, we opted for a total abdominal hysterectomy instead of a laparoscopic myomectomy, due to an elevation of LDH5/LDH1 ratio and CT findings indicative of sarcoma. Histological examination revealed a high grade leiomyosarcoma, confirming our suspicion. Thus, we had avoided the risks linked to morcellation. CONCLUSIONS: Our experience suggests that LDH isoenzymes assessment may be relevant in preoperative diagnosis of uterine sarcoma. Further studies are necessary to determine its role in a diagnostic algorithm. We think it may be useful especially for patients with clinical or ultrasonographic suspicion of uterine sarcoma not confirmed by imaging techniques. Furthermore, the role of less considered imaging techniques, such as CT, should not be underestimated in challenging cases.

Loop Electrosurgical Excision Procedure versus Cryotherapy in the Treatment of Cervical Intraepithelial Neoplasia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

AIM: Invasive cervical cancer is proceeded by a phase of preinvasive disease that is slow to progress and can be detected, treated, and collectively referred to as cervical intraepithelial neoplasia (CIN). Several excisional and ablative treatments for CIN have been studied, with loop electrosurgical excision procedure (LEEP) and cryotherapy being the two most commonly utilized. The objective of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to compare the compare harms and benefits of LEEP versus cryotherapy in women with CIN. METHODS: Electronic databases were searched from their inception until May 2018. We included all RCTs comparing cryotherapy versus LEEP in women with CIN. We included trials evaluating both HIV-seropositive and HIV-seronegative women. The primary outcome was the persistence of the disease at 6-month follow-up. Meta-analysis was performed using the random-effects model to produce summary treatment effects in terms of relative risk (RR) with 95% confidence interval (CI). RESULTS: Four trials, including 1035 women with CIN, were identified as relevant and included in the meta-analysis. Women who received LEEP for CIN had a significantly lower persistence at 6-month follow-up biopsy (RR: 0.87, 95% CI: 0.76-0.99) and significantly lower recurrence at 12-month follow-up biopsy (RR: 0.91, 95% CI: 0.84-0.99) compared to those who received cryotherapy. No between-group differences were found in the complications rate, but the analyses were not powered for these outcomes. CONCLUSIONS: In women with CIN, treatment with LEEP was associated with a significantly lower risk of persistence disease at 6 months and recurrence disease at 12 months compared to treatment with cryotherapy.

Metabolomic Signature of Endometrial Cancer.

Endometrial cancer (EC) is the most common cancer of the female reproductive tract in developed countries. At the moment, no effective screening system is available. Here, we evaluate the diagnostic performance of a serum metabolomic signature. Two enrollments were carried out, one consisting of 168 subjects: 88 with EC and 80 healthy women, was used for building the classification models. The second (used to establish the performance of the classification algorithm) was consisted of 120 subjects: 30 with EC, 30 with ovarian cancer, 10 with benign endometrial disease, and 50 healthy controls. Two ensemble models were built, one with all EC versus controls (Model I) and one in which EC patients were aggregated according to their histotype (Model II). Serum metabolomic analysis was conducted via gas chromatography-mass spectrometry, while classification was done by an ensemble learning machine. Accuracy ranged from 62% to 99% for the Model I and from 67% to 100% for the Model II. Ensemble model showed an accuracy of 100% both for Model I and II. The most important metabolites in class separation were lactic acid, progesterone, homocysteine, 3-hydroxybutyrate, linoleic acid, stearic acid, myristic acid, threonine, and valine. The serum metabolomics signature of endometrial cancer patients is peculiar because it differs from that of healthy controls and from that of benign endometrial disease and from other gynecological cancers (such as ovarian cancer).

DJ-1 is a reliable serum biomarker for discriminating high-risk endometrial cancer.

New reliable approaches to stratify patients with endometrial cancer into risk categories are highly needed. We have recently demonstrated that DJ-1 is overexpressed in endometrial cancer, showing significantly higher levels both in serum and tissue of patients with high-risk endometrial cancer compared with low-risk endometrial cancer. In this experimental study, we further extended our observation, evaluating the role of DJ-1 as an accurate serum biomarker for high-risk endometrial cancer. A total of 101 endometrial cancer patients and 44 healthy subjects were prospectively recruited. DJ-1 serum levels were evaluated comparing cases and controls and, among endometrial cancer patients, between high- and low-risk patients. The results demonstrate that DJ-1 levels are significantly higher in cases versus controls and in high- versus low-risk patients. The receiver operating characteristic curve analysis shows that DJ-1 has a very good diagnostic accuracy in discriminating endometrial cancer patients versus controls and an excellent accuracy in distinguishing, among endometrial cancer patients, low- from high-risk cases. DJ-1 sensitivity and specificity are the highest when high- and low-risk patients are compared, reaching the value of 95% and 99%, respectively. Moreover, DJ-1 serum levels seem to be correlated with worsening of the endometrial cancer grade and histotype, making it a reliable tool in the preoperative decision-making process.

Corrigendum to "The Efficacy of Inositol and N-Acetyl Cysteine Administration (Ovaric HP) in Improving the Ovarian Function in Infertile Women with PCOS with or without Insulin Resistance".

[This corrects the article DOI: 10.1155/2014/141020.].

Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients.

High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10-0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p < 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment.

Adenomyosis: What the Patient Needs.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 28-year-old patient, attempting pregnancy for 1 year, with severe cyclic pelvic pain and with clinical examination and imaging techniques suggestive of adenomyosis. Many questions this paradigmatic patient may pose to the clinician are addressed, and all clinical scenarios are discussed. A decision algorithm derived from this discussion is also proposed.

Prophylactic bilateral salpingectomy for the prevention of ovarian cancers: What is happening in Italy?

In 2011, the Society of Gynecologic Oncology of Canada encouraged physicians to discuss with their patients the risks and benefits of prophylactic bilateral salpingectomy (PBS) at the time of hysterectomy or tubal ligation for prevention of ovarian cancers (OCs). The aim of this study was to examine obstetrician-gynaecologists' knowledge, opinions and practice patterns relating to opportunistic salpingectomy in the general population. An anonymous electronic survey was sent to residents, academic and hospital staff in Italian OBGYN departments. The survey included questions on demographics, knowledge and attitudes in terms of the implementation of PBS in women at average population risk of OC. At least 80% of the 479 respondents reported performing PBS during hysterectomy for benign indications, chiefly with the intent of OC risk reduction but also to decrease the risk of reoperation and subsequent tubal pathologies. Among the 86 colleagues who do not routinely perform PBS, more than 50% stated that they have doubts regarding the benefits associated with the procedure. Most of the respondents declared that they were familiar with the literature on the topic and were aware of the data reporting the safety of the procedure, and only 21 (4.53%) had never heard of PBS. Over 40% of the respondents worked in hospitals in southern Italy. PBS as a prophylactic measure to reduce the incidence of OC is a well-known strategy among the Italian OBGYNs interviewed. Given the unequal distribution of respondents, however, wider educational initiatives should be undertaken, at least in Italy, to increase the implementation of salpingectomy among OBGYNs.

Wide excision of soft tissues adjacent to the ovary and fallopian tube does not impair the ovarian reserve in women undergoing prophylactic bilateral salpingectomy: results from a randomized, controlled trial.

OBJECTIVE: To study the effects of the wide excision of soft tissues adjacent to the ovary and fallopian tube on ovarian function and surgical outcomes in women undergoing laparoscopic bilateral prophylactic salpingectomy. DESIGN: Randomized, controlled trial. SETTING: Teaching hospital. PATIENT(S): One hundred eighty-six women undergoing laparoscopic surgery for uterine myoma (n = 143) or tubal surgical sterilization (n = 43). INTERVENTION(S): Patients were randomly divided into two groups. In group A (n = 91), standard salpingectomy was performed. In group B (n = 95), the mesosalpinx was removed within the tubes. Prior to and 3 months after surgery, antimüllerian hormone (AMH), FSH, three-dimensional antral follicle count (AFC), vascular index (VI), flow index (FI), vascular-flow index (VFI), and OvAge were recorded for each patient. MAIN OUTCOME MEASURE(S): Ovarian reserve modification (Δ) before and after surgery was assessed as the primary outcome. Operative time, variation of the hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were assessed as secondary outcomes. RESULT(S): No significant difference was observed between groups for ΔAMH, ΔFSH, ΔAFC, ΔVI, ΔFI, ΔVFI, and ΔOvAge. Moreover, the groups were similar for operative time, ΔHb, postoperative hospital stay, postoperative return to normal activity, and complication rate. CONCLUSION(S): Even when the surgical excision includes the removal of the mesosalpinx, salpingectomy does not damage the ovarian reserve. Moreover, wide salpingectomy with excision of the mesosalpinx did not alter blood loss, hospitalization stay, or return to normal activities. CLINICAL TRIAL REGISTRATION NUMBER: NCT02086370.

Failure to recognize preoperatively high-risk endometrial carcinoma is associated with a poor outcome.

OBJECTIVE: To evaluate the misdiagnosis between endometrial biopsy and definitive surgical pathology and to assess whether the failure in recognizing preoperatively high-risk endometrial carcinoma (EC) can impact oncological outcomes. STUDY DESIGN: A retrospective study was conducted to evaluate patients with EC diagnosed by preoperative endometrial biopsy who subsequently underwent surgical staging between 2006 and 2013 at our institution. In patients with a surgical diagnosis of high-risk EC, histotype and grade change between the endometrial biopsy and surgical specimen (discordance diagnosis) were evaluated and correlated to survival outcomes. Cox's regression model for multivariable analysis was used to evaluate the effect of several variables (age, stage, discordance in diagnosis, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy) on the survival rate. RESULTS: Data from 447 patients were reviewed. Among 109 women with surgical diagnosis of high-risk EC, 35 (32.1%) were preoperatively misdiagnosed. Of these 35 women, 24 (68.6%) cases were upgraded to grade 3, and 11 (3.4%) were upgraded to serous or clear cell type in the definitive specimen. The 5-year overall survival (OS; 70.2 vs. 86.8%; p=0.029), disease-specific survival (DSS; 72.5 vs. 88.2%; p=0.039) and recurrence free survival (RFS; 62.6 vs. 82.5%; p=0.024) were significantly lower in the high-risk EC patients who were preoperatively undiagnosed in the endometrial biopsy compared with patients with an appropriate preoperative histological diagnosis. Controlling for age, stage, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy, multivariable analysis revealed that discordance in diagnosis was associated with poorer survival outcomes. CONCLUSION: Failure to recognize preoperatively high-risk ECs is associated with worse outcomes.

Polycystic ovary syndrome: chemical pharmacotherapy.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disease among women of childbearing age. The clinical features are heterogeneous and vary in intensity. Hirsutism, menstrual disorders and infertility are the most frequent conditions observed; however, long-term complications (dyslipidemia, hypertension, cardiovascular disease, type 2 diabetes mellitus, endometrial cancer) are also often described. Each disorder may be managed by tailored strategies, employing sequential or combined pharmacological and/or non-pharmacological treatment. AREAS COVERED: The authors review the drugs used for PCOS management and discuss new approaches. A systematic MEDLINE search regarding the randomized controlled trials, retrospective and observational studies about medical treatments of PCOS, the Cochrane library for reviews and also search for registered trials on ClinicalTrials.gov is performed. EXPERT OPINION: A uniform treatment for PCOS patients does not exist. Clinicians should perform an accurate evaluation of patients' characteristics, identifying the phenotypic target and, subsequently, the best-tailored treatment to manage one or more clinical issues. Lifestyle intervention should always be the first recommended approach unless other issues indicate that drug or hormonal interventions are superior.

How to Manage Bowel Endometriosis: The ETIC Approach.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 35-year-old patient desiring pregnancy with a history of previous surgery for endometrioma and bowel obstruction symptoms. Many questions that this paradigmatic patient may pose to the clinician are addressed, and various clinical scenarios are discussed. A decision algorithm derived from this discussion is proposed as well.

Sonographic findings in postmenopausal women with a prior endometrial ablation: interpretation and management of women with endometrial thickening and bleeding.

OBJECTIVE: To understand the meaning of endometrial thickening and bleeding in postmenopausal women who had previously undergone endometrial ablation (EA). DESIGN: Retrospective observational study. Canadian Task Force III. SETTING: Obstetrics and Gynecology Unit, Magna Graecia University, Catanzaro, Italy. PATIENTS: Sixty-three postmenopausal women who had previously undergone EA. INTERVENTIONS: A retrospective evaluation of clinical charts of postmenopausal women who had a follow-up visit after EA between January 2000 and August 2014. MEASUREMENTS AND MAIN RESULTS: The rates of endometrial thickening (with or without bleeding), endometrial atrophy, and cancer were determined. Postmenopausal bleeding was reported in 9 patients (14.3%). Endometrial thickening was observed in 51 patients (80.9%; mean ± SD endometrial thickness, 7.7 ± 3.0 mm). A significantly (p < .05) greater number of patients with an endometrial thickness of 5 to 10 mm was observed compared with those with an endometrial thickness of <5 mm or >10 mm. A significant (p = .001) difference in increase in endometrial thickness was observed between patients with and without bleeding. Overall, hysteroscopy plus endometrial biopsy was scheduled in 24 patients. In all bleeding women, a histological diagnosis of endometrial atrophy was demonstrated. Concerning bleeding-free women, in 14 patients with endometrial thickening of >10 mm, mucosal atrophy was detected. The only bleeding-free patient in whom an endometrial echogenic fluid collection was detected had a histological diagnosis of endometrioid endometrial cancer. Thus, patients who underwent hysteroscopy had a 95.8% rate of mucosal atrophy and a 4.2% rate of endometrial cancer. The overall cancer rate in our global population (menopause with previous EA) was 1.6%. CONCLUSION: Postmenopausal bleeding and sonographic detection of endometrial thickening in patients with previous EA are not necessarily related to a malignant disease. Nonetheless, ultrasound visualization of endometrial thickening plus an echogenic endometrial fluid collection in these patients always warrants an invasive diagnostic procedure regardless of whether or not bleeding is reported.

The Efficacy of Inositol and N-Acetyl Cysteine Administration (Ovaric HP) in Improving the Ovarian Function in Infertile Women with PCOS with or without Insulin Resistance.

Objective. Substances such as inositol and N-acetylcysteine (NAC) have been recently shown to be effective in treatment of PCOS patients. The aim of this prospective trial is to evaluate the efficacy of NAC + Inositol + folic acid on ovulation rate and menstrual regularity in PCOS patients with and without insulin resistance. Methods. Among the 91 PCOS patients treated with NAC + Inositol + folic, insulin resistance was present in 44 subjects (A) and absent in 47 (B). The primary endpoint was the ovulation rate/year, determined by menstrual diary, serum progesterone performed between 21° and 24° days, ultrasound findings of growth follicular or luteal cysts, and luteal ratio. HOMA-index assessment after 6 and 12 months of treatment was evaluated as secondary endpoint. Results. In both groups there was a significant increase in ovulation rate and no significant differences were found in the primary outcome between two groups. In group A, a significant reduction of HOMA-index was observed. Conclusions. The association NAC + Inositol + folic, regardless of insulin-resistance state, seems to improve ovarian function in PCOS patients. Therefore, inositol and NAC may have additional noninsulin-related mechanisms of action that allow achieving benefits also in those patients with negative HOMA-index.

DJ-1 in endometrial cancer: a possible biomarker to improve differential diagnosis between subtypes.

OBJECTIVE: The objectives of this study were to characterize the well-defined endometrial cancer (EC) type I (endometrioid [EEC] G1-G2) versus the prototype of EC type II (serous [ESC]) and to evaluate the expression of specific biomarkers differentially expressed between 2 well-defined types, in those EC subtypes (such as EEC G3) disputed between types I and II. METHODS: Data from 25 patients (10 EEC G1-G2, 8 EEC G3, 5 ESC, and 2 clear cell) submitted to the surgical treatment were collected. Two-dimensional electrophoresis and mass spectrometry (MS) analysis were performed on 5 EEC G1-G2 and 5 healthy endometrial samples of the same patients. Differentially expressed proteins, such as DJ-1, were validated by Western blot. In patients with EEC G1-G2, serum levels of DJ-1, an overexpressed oncoprotein related to EC pathogenesis and progression, were evaluated and then compared with levels identified in patients with ESC and healthy controls. The DJ-1 immunohistochemical (IHC) staining was performed on neoplastic and healthy endometrium collected from the same patients. The 8 stored samples of EEC G3 were submitted to DJ-1 IHC assays. RESULTS: The 2-dimensional electrophoresis analysis identified 1040 protein spots differentially expressed in EEC G1-G2 compared with healthy endometrium. Forty-two spots were subjected to liquid chromatography-MS/MS analysis. Thirty-three up-regulated (like an annexin 2 [ANXA2] shorter isoform, CAPG [macrophage-capping protein], DJ-1/PARK7) and 9 down-regulated (like calreticulin and ubiquitin carboxyl-terminal hydrolase isozyme L1) proteins were identified and validated by Western blot. A significant increase in serum DJ-1 levels of EEC G1-G2 versus the healthy controls and in ESC versus EEC patients was observed. DJ-1 IHC score was significantly higher in ESC versus those EEC G1-G2. In 3 cases of EEC G3, the DJ-1 expression was similar to the ESC subtype. CONCLUSIONS: The identification of proteins, such as DJ-1, differentially expressed, between well-defined EC types I and II allows to make a subtype-specific presurgical diagnosis and help surgeon to safely preoperatively choose a proper surgical treatment.

Adjuvant use of platelet gel for wound breakdown prevention in advanced vulvar cancer surgery: a retrospective study.

OBJECTIVE: The aggressive surgical strategy adopted for vulvar cancer is related to a high complication rate, usually consisting in infections and wound breakdown. Considering that platelet gel concentrate improves reparation of cutaneous lesions, the aim of the current retrospective study was to evaluate the efficacy of platelet gel application in women who had undergone radical surgery for vulvar cancer. MATERIALS AND METHODS: We retrospectively analyzed record charts of 25 women referred to our academic departments with a diagnosis of vulvar cancer and who had undergone radical vulvectomy plus inguinofemoral lymphadenectomy between January 2007 and December 2011. During the reconstructive phase, a platelet gel was placed on the vaginal breach in 10 women (group A). In the remaining 15 patients, only surgical strategies were performed (group B). Primary outcomes were wound infection, necrosis, and/or breakdown of wounds rates; secondary outcomes were postoperative fever, hospital stay, and lastly, wound healing. RESULTS: Compared to surgery alone, the platelet gel application was related to a significant decrease in wound infection (P = 0.032), necrosis of vaginal wounds (P = 0.096), and breakdown wound (P = 0.048) rates. In addition, in group A, reduction in postoperative fever rate (P < 0.001) and hospital stay (P < 0.001) were also detected. Compared to surgery alone, a faster wound healing in patients who had undergone surgery plus platelet (P < 0.001) were lastly observed. CONCLUSION: In conclusion, platelet gel application before vulvar reconstruction represents an effective strategy to prevent wound breakdown after local advanced vulvar cancer surgery. However, further prospective data are needed to confirm these preliminary results.