Adult-Type Granulosa Cell Tumor with Similar Clinical Findings Seen during Ovarian Cystectomy Performed at the Same Time as Laparoscopic Ovarian Drilling for Polycystic Ovarian Syndrome: An Extremely Rare Case

Polycystic ovary syndrome (PCOS) is a major cause of anovulatory infertility. Laparoscopic ovarian drilling (LOD) is a treatment for PCOS that allows the laparoscopic identification of other intra-abdominal lesions and the provision of diagnostic treatment. This study reports a case of PCOS with an ovarian mass in which LOD was aggressively used and a granulosa cell tumor (GCT) was found. A 34-year-old woman with secondary amenorrhea and irregular menstrual cycles presented to the emergency department with abdominal pain of unknown etiology. Imaging studies revealed a 6-cm left ovarian mass with an internal appearance suggestive of a hemorrhage. The patient’s secondary amenorrhea was subsequently diagnosed as PCOS, and LOD was performed to preserve her fertility. Simultaneously, a cystectomy was performed to evaluate the tumor in the left ovary;the diagnosis was adult-type GCT. Although concomitant GCT and PCOS are extremely rare, the two conditions have similar clinical manifestations. In women of reproductive age, the impact of surgery on future fertility should be considered, and the initial surgical technique should be chosen carefully.

Oncology and reproductive outcomes over 16 years of malignant ovarian germ cell tumors treated by fertility sparing surgery

BACKGROUND Malignant ovarian germ cell tumors(MOGCT)are rare and frequently occur in women of young and reproductive age and the oncologic and reproductive outcomes after fertility-sparing surgery(FSS)for this disease are still limited.AIM To evaluate the oncology and reproductive outcomes of MOGCT patients who underwent FSS.METHODS All MOGCT patients who underwent FSS defined as the operation with a preserved uterus and at least one side of the ovary at our institute between January 2005 and December 2020 were retrospectively reviewed.RESULTS Sixty-two patients were recruited for this study.The median age was 22 years old and over 77%were nulliparous.The three most common histology findings were immature teratoma(32.2%),dysgerminoma(24.2%),and yolk sac tumor(24.2%).The distribution of stage was as follows;Stage I,74.8%;stage II,9.7%;stage III,11.3%;and stage IV,4.8%.Forty-three(67.7%)patients received adjuvant chemotherapy.With a median follow-up time of 96.3 mo,the 10-year progressionfree survival and overall survival were 82.4%and 91%,respectively.For reproductive outcomes,of 43 patients who received adjuvant chemotherapy,18(41.9%)had normal menstruation,and 17(39.5%)resumed menstruation with a median time of 4 mo.Of about 14 patients who desired to conceive,four were pregnant and delivered good outcomes.Only one case was aborted.Therefore,the successful pregnancy rate was 28.6%CONCLUSION The oncology and reproductive outcomes of MOGCT treated by FSS are excellent.Many patients show a long survival time with normal menstruation.However,the obstetric outcome is not quite satisfactory.

Ovarian desmoplastic small round cell tumors: Prognosis is poor! Case report

The tumor desmoplastic small round cell in women is rare. Ovarian its location is exceptional. We report a patient of 20 years, the originalNorth Africawho consulted for an increase in abdominal volume with impaired general condition. Pelvic ultrasonography and computed tomography were in favor of multiple peritoneal masses with ascites. After surgical exploration, the histological and immunohistochemical data for diagnosis small round cell desmoplastic tumor of ovarian the patient was a candidate for poly chemotherapy but she was died a month later. Diagnosis relies on histological and immunohistochemical data. The demonstration of a nonrandom translocation t (11;22) (p13;q12) is specific for the disease. The management is multidisciplinary and combining surgery, a poly aggressive chemotherapy and radiotherapy. The prognosis remains poor.

Effects of DC-CIK cell immunotherapy combined with chemotherapy on immune function, coagulation function and tumor stem cell markers in patients with recurrent ovarian cancer

Objective: To investigate the effects of immunotherapy with dendritic cells (DC)-cytokine induced killer cells (CIK) combined with chemotherapy on immune function, coagulation function and tumor stem cell markers in patients with recurrent ovarian cancer. Methods: A total of 80 cases in our hospital for treatment of recurrent ovarian cancer patients were selected as the research object, they were divided into chemotherapy group (n=35) and combined treatment group (n=45) according to whether or not to receive cellular immunotherapy, chemotherapy group received TC chemotherapy, combined therapy group were given DC-CIK cell immunotherapy combined with TC chemotherapy group, the two groups were treated with 21 d for a cycle, 3 cycles were treated;The changes of immune function, coagulation function and tumor stem cell markers were compared between the day of blood collection and the end of treatment for 7 d. Results: After the end of treatment for 7 d, the CD3+, CD3+CD4+, CD4+/CD8+, NK cell number of combined treatment group were significantly higher than that of blood collection day, the number of CD4+ CD25+ was significantly lower than that of blood collection day, The improvement of peripheral blood T lymphocyte subsets in the combined treatment group was better than that in the chemotherapy group;After the end of treatment for 7 d, the FIB levels of two groups were significantly decreased than those of the blood collection day, the difference was statistically significant;After the end of treatment for 7 d, the CD133 and DDX4 levels of two groups were significantly lower than that of the blood collection day, and the combined treatment group was significantly lower than the chemotherapy group, the difference were statistically significant. Results: DC-CIK cell immunotherapy combined with chemotherapy can significantly improve the immunity and the level of FIB of patients with recurrent ovarian cancer, and regulating the level of serum tumor stem cell markers in patients, it has positive significance to improve the prognosis of patients, and is worthy of popularization and application in clinic.

Aiming to immune elimination of ovarian cancer stem cells

Ovarian cancer accounts for only 3% of all cancers in women, but it causes more deaths than any other gynecologic cancer. Treatment with chemotherapy and cytoreductive surgery shows a good response to the therapy. However, in a large proportion of the patients the tumor grows back within a few years. Cancer stem cells, that are less responsive to these treatments, are blamed for this recurrence of disease. Immune therapy either cellular or humoral is a novel concept to treat cancer. It is based on the notice that immune cells invade the tumor. However, the tumor invest heavily to escape from immune elimination by recruiting several immune suppressive mechanisms. These processes are normally in place to limit excessive immune activation and prevent autoimmune phenomena. Here, we discuss current knowledge about the immune(suppressive)status in ovarian cancer. Moreover, we discuss the immunological targets of ovarian cancer stem cells.

Therapeutic strategies for targeting the ovarian tumor stroma

Epithelial ovarian cancer is the most lethal type of gynecologic malignancy. Sixty percent of women who are diagnosed with ovarian cancer present with advancedstage disease that involves the peritoneal cavity and these patients have a 5-year survival rate of less than 30%. For more than two decades, tumor-debulking surgery followed by platinum-taxane combination chemotherapy has remained the conventional first-line treatment of ovarian cancer. Although the initial response rate is 70%-80%, most patients with advancedstage ovarian cancer eventually relapse and succumb to recurrent chemoresistant disease. A number of molecular aberrations that drive tumor progression have been identified in ovarian cancer cells and intensive efforts have focused on developing therapeutic agents that target these aberrations. However, increasing evidence indicates that reciprocal interactions between tumor cells and various types of stromal cells also play important roles in driving ovarian tumor progression and that these stromal cells represent attractive therapeutic targets. Unlike tumor cells, stromal cells within the tumor microenvironment are in general geneticallystable and are therefore less likely to become resistant to therapy. This concise review discusses the biological significance of the cross-talk between ovarian cancer cells and three major types of stromal cells(endothelial cells, fibroblasts, macrophages) and the development of new-generation therapies that target the ovarian tumor microenvironment.

Apoptosis and Expression of Protein TRAIL in Granulosa Cells of Rats with Polycystic Ovarian Syndrome

The relationship between apoptosis of granulosa cells and follicle development arrest in polycystic ovarian syndrome (PCOS) rats, and the contribution of tumor necrosis factor related apoptosis inducing ligand (TRAIL) in apoptosis of granulosa cells were explored. By using sodium prasterone sulfate rat PCOS model was induced. The apoptosis of granulosa cells in ovaries of rats was observed by TdT-mediated dUTP-biotin nick end-labeling (TUNEL), and the expression of TRAIL protein and mRNA in granulosa cells was detected by using immunhistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) respectively. The apoptotic rate and the expression of protein TRAIL in granulosa cells were significantly higher in antral follicles from the PCOS rats than in those from the control rats (P<0.01, P<0.05). There was no significant difference in apoptotic rate and the expression of TRAIL protein in granulosa cells of preantral follicles between the PCOS rats and the control rats (P>0.05). No apoptosis and the expression of TRAIL protein in granulosa cells of primordial follicles were found in the two groups. The expression of TRAIL mRNA was significantly stronger in granulosa cells from the PCOS rats than in those from the con- trol rats (P<0.01). It was suggested that the apoptotic rate in granulosa cells was significantly higher in antral follicle from the PCOS rats than in those from the control rats. TRAIL played a role in regu- lating the apoptosis of granulosa cells in PCOS rats.

EFFECTS AND MECHANISMS OF ENDOSTATIN ON THE GROWTH OF OVARIAN CANCER SKOV_3 CELLS IN VITRO AND IN VIVO

Objective： To evaluate the inhibitory effect of Endostatin on ovarian cancer cell line SKOV3 and to investigate the possible mechanism of the inhibition. Methods： Using MTT, transmission electron microscope （TEM） and immunocytochemistry, the effects of Endostatin on the proliferation of SKOV3 cells were studied. Nude mice were subcutaneously implanted with SKOV3 cells. The cell apoptosis of implanted tumor was detected by TUNEL and TEM. The expressions of bcl-2 and bax in implanted tumor tissues were measured by RT-PCR and immunohistochemistry. Results： Endostatin significantly inhibited the proliferation of SKOV3 cells in vitro （P〈0.01） and induced cell apoptosis, whereas the expressions of bcl-2 and bax were not changed obviously in SKOV3 cell treated with Endostatin. The mean tumor weight of Endostatin treated group was markedly lower than that of PBS control group （P〈0.05）. The expression of bcl-2 was down-regulated in Endostatin treated group, but bax was not influenced. Conclusions： The results demonstrated that Endostatin might have anti-tumor effect on ovarian carcinoma. One of the important mechanisms of Endostatin effect of anti-angiogenic and anti-tumor activities might involve regulating the bcl-2/bax expression and inducing apoptosis.

Effects of HLEC on the secreted proteins of epithelial ovarian cancer cells prone to metastasize to lymph nodes

Objective： To study explores the effect of HLEC on the secreted proteins of epithelial ovarian cancer （EOC） cells （SKOV3-PM4） with directional highly lymphatic metastasis. Methods： Supernatants of four groups of cultured cells, namely, SKOV3 （A）, SKOV3＋HLEC （B）, SKOV3-PM4 （C）, SKOV3-PM4＋HLEC （D）, were collected, and their proteins were detected by antibody arrays and iTRAOcZD-LC-MALDI- TOF/TOF/MS. Significantly differential proteins were further analyzed via bioinformatics and validated in human serums and cell media via ELISA. Results： Results of antibody arrays and mass spectrometry demonstrated that GRN and VEGFA were upregulated in group C （compared with group A）, whereas IGFBP7 and SPARC were downregulated in group D （compared with group C）. Comprehensive bioinformatics analysis results showed that IGFBP7 and VEGFA were closely linked to each other. Further validation with serums showed statistical significance in VEGFA and IGFBP7 levels among groups of patients with ovarian cancers, benign tumors, and control groups. Two proteins were upegulated in the first group. VEGFA in the control group was downregulated. For IGFBP, upregulation in the control group and down-regulation in the first group were also observed. Conclusion： The HLEC microenvironment is closely associated with directional metastasis to lymph nodes and with differential proteins including cell stromal proteins and adhesion factors. The upregulation of VEGFA and GRN and the downregulation of SPARC and IGFBP7 are closely associated with directional metastasis to lymph nodes in EOC cells.

THE MODIFIED RADIOIMMUNOASSAY OF SERUM INHIBIN AND ITS VALUE IN MONITORING OVARIAN TUMOR

Objectives and Methods: A modified radioimmunoassay (RIA) of serum inhibin (INH) was developed and applied to measure serum INH contents in 39 fertile and 16 postmenopausal women. Thirty-three cases of ovarian tumors, including granulosa cell tumors and other kinds of ovarian tumors, were monitored by serum INH RIA. Results: The mean value of serum INH contents in follicular, peri-ovulatory and mid-luteal phases of fertile women were 9.48±7.10 pg/ml (2.04～18.53pg/ml), 19.04±9.73 pg/ml (3.49～33.26 pg/ml) and 131.13±110.81 pg/ml (3.49～ 341.10 pg/ml), respectively. Serum INH concentration was negatively correlated with serum FSH concentration, (rs=?0.483,P<0.01). Serum IHN contents were less than 3.6 pg/ml in normal postmenopausal women. The mean value of serum INH contents in ovarian granulosa cell tumor, thecoma, mucinous cystadenocarcinoma and malignant teratoma cases were significantly higher than that of other ovarian tumors, (P<0.01). Serum INH contents were elevated in ovarian granulosa cell tumor, thecoma, mucinous cystadenocaricinoma and endometrioid carcinoma cases with serum CA-125 values in normal range before operation, but serum INH contents decreased to normal range within one week after operation. And consecutive serum INH RIA could be a valuable tool in monitoring for therapeutic effect. Conclusion: Modified INH RIA was of convenient, time-saving and quantitative characteristics, especially with its high sensitivity (<1 pg/ml). There was a regular change of serum INH concentrations during menstrual cycle. INH could inhibit the synthesis and secretion of follicle stimulating hormone (FSH). INH would become a valuable marker for ovarian tumor. INH RIA combined with the measurement of serum CA-125 would be helpful to the early diagnosis, treatment and follow-up for ovarian cancer.

Ovarian Sex Cord-Stromal Tumors in Postmenopausal Women and Total Laparoscopical Management

BACKGROUND: Ovarian sex-cord stromal tumors (SCST) take up 5% of the ovarian neoplasm and may develop in?to?an ovarian mass or a haemoperitoneum. The surgical management of SCST in early-stage adult patients is not well?defined. CASE REPORT: A 69 year-old postmenopausal woman was admitted for metrorrhagia, a right ovary mass and?increasing pelvic pain. Preoperative clinical and instrumental examination suspected an ovarian tumor, and the?laparoscopic right ophorectomy and the frozen section suggested an ovarian SCST. To fast restore and preserve woman?integrity, total laparoscopic hysterectomy (TLH) plus left salpingo-ophorectomy (SO) were performed, without complications?in the short and long term follow-up. CONCLUSION: In the authors’ opinion, the minimally invasive management?of SCST by TLH plus bilateral SO followed by a prolonged surveillance and without intensive surgical staging,?could be an appropriate clinical and surgical choice in elder patient at early stage, since these tumors are slow at?growth, recurring locally and only a long time after initial treatment. We suggest, after a minimally invasive treatment,?a possible “wait and see” option, as in our case report.

A Retrospective Study of Ovarian Sex Cord Stromal Tumors at the Egyptian National Cancer Institute

Background: Ovarian sex cord-stromal tumors are an uncommon heterogeneous group of tumors with different biological behaviors and clinico-patho- logic aspects. Aim of the Work: This study will review the clinico-pathologic aspects of sex-cord stromal ovarian tumors at the National Cancer Institute (NCI), Cairo University, Egypt, as well as their management and follow-up regarding disease free survival and overall survival. Patients and Methods: This retrospective study was conducted at the National Cancer Institute Cairo University, Egypt on female patients with ovarian sex cord stromal tumors in the period from January 2008 to December 2012 with a follow-up period of 24 to 84 months. The age of the patients, different clinical presentations, radiological findings, associated uterine bleeding (need for endometrial biopsy), pre-operative CA125 levels, surgical management done, different histopathological types, different biological behaviors, presence of ascites (and its correlation with the histopathology), Adjuvant chemotherapy (according to biological behavior and pathological type), and follow-up of non-benign cases for up to 84 months will all be documented and studied. Results: The mean age at presentation was 47.34;abdominal pain and mass were the commonest presentations 54.5% and 53.2% respectively;the main radiologic findings were a pelvic mass +/- ascites which had no correlation to the pathological type (p = 0.075). Endometrial hyperplasia and endometrial carcinoma were associated with 22% and 2.5% of cases respectively. Stages I and II represented 95% of patients with non-benign tumors (48 patients). Panhysterectomy +/- infracolic omentectomy or fertility sparing surgery were done in 70.1% and 29.9% of patients respectively. AGCTs were the commonest pathological type (49.4%). Adjuvant chemotherapy was given to 14 patients (46.7%) with non-benign tumors. 6 recurrences (20%) in 30 patients with non-benign tumors on regular follow-up were documented. The median of disease free survival (DFS) was 50.5 months. The median overall survival was 49.5 months. Conclusion: Ovarian SCSTs are uncommon neoplasms with different biological behaviors where AGCTs are the commonest among Egyptian females. Hormonal manifestations are uncommon where abnormal vaginal bleeding is the commonest one. The presence of ascitic fluid has no correlation with the pathological type of the tumor. Early stages (I and II) represented about 95% of non-benign tumors. Surgical management without lymphadenectomy +/- adjuvant chemotherapy is the main line of treatment at our institute. The OS was shorter than that documented in the literature. A small number of patients, reluctance of follow-up and unavailability of some patients’ data were the main drawbacks in this study.

Sertoli-Leydig Cell Tumor from Latifa Hospital, Dubai UAE: Case Report

Sertoli-Leydig cell tumors (SLCTs) are rare tumors. Mass and pain are the presenting feature. The varying histopathology and differentiation of this tumor present difficulties with proper diagnosis and development of optimal treatment regimens. The prognosis depends on tumors grading and staging. Surgery is main stay management option. Chemotherapy and radiation options are still of choice.?We aimed?to?present Sertoli-Leydig cell tumor managed surgical at Latifa Hospital in Dubai, UAE with acceptable outcome and good patient satisfaction.

Dietary Conjugated Linoleic Acids Arrest Cell Cycle Progression and Prevent Ovarian Cancer Xenografts Growth Suggesting a Trans-10 Cis-12 Isoform Specific Activity

Therapies for treating ovarian cancer (OvCa) successfully are largely inadequate. Alternative therapies and diet(s) with preventive potential to debilitated onset, and reduced OvCa tumor burden in situ, have not been systematically studied. Preventive role of conjugated linoleic acids (CLAs) has been reported in many other cancers. We report the first systematic in vitro and in vivo study modeling potential preventive mechanism(s) of CLA, an octadecadienolic fatty acid in clear cell OvCa cell line TOV-21G. We demonstrate that a dose and time-dependent down-regulation of cyclin E and A proteins (p 0.05) by CLA (t10,c12) was concomitant with cell cycle arrest of TOV-21G cell lines in S phase. To understand the molecular mechanism underlying CLA (t10,c12) induced S phase arrest, levels of cell cycle regulatory proteins were determined by western blot analyses. Exposure to CLA (t10,c12) increased p21(CIP1/WAF1), and p27(KIP1) protein levels in a time and dose-dependent manner. Interestingly CLA (t10,c12) did not significantly affect protein levels of cyclin-dependent kinase (cdk) 2, and p53, however, hyperphosphorylated form of pRb (p 0.05) was abrogated. Exposure to CLA (c9,t11) indicated a modest increase in p21(CIP1/WAF1) and p27(KIP1) levels, but changes in cyclin A and E levels were statistically insignificant. These results indicate that CLA (t10,c12) mediated p27(KIP1) upregulation and inhibition of hyperphosphorylation of ppRb may be the possible mechanism for the S phase arrest in TOV-21G cell line. Our in vivo data showed that CLA reduced the progression of TOV-21G xenografts by >50%. Together our results provide evidence of CLA exerted preventive effect on OvCa cell and tumor growth. Tumor growth arrest may be resultant from CLA (t10,c12) mediated modulation of cell cycle arrest.

Chemosensitivity Testing of Circulating Epithelial Tumor Cells (CETC) in <i>Vitro</i>: Correlation to in <i>Vivo</i>Sensitivity and Clinical Outcome

Background: Chemotherapy is a mainstay of tumor therapy, however, it is predominantly applied according to empirically developed recommendations derived from statistical relapse rates occurring years after the treatment in the adjuvant situation and from progression-free interval data in the metastatic situation, without any possibility of individually determining the efficacy in the adjuvant situation and with loss of time and quality of life in the metastatic situation if the drugs chosen are not effective. Here, we present a method to determine the efficiency of chemotherapeutic drugs using tumor cells circulating in blood as the part of the tumor actually available in the patient’s body for chemosensitivity testing. Methodology/Principal Findings: After only red blood cell lysis, omitting any enrichment (analogous to other blood cell enumeration methods, including rare CD34 cells), the white cells comprising the circulating epithelial tumor cells (CETC) are exposed to the drugs in question in different concentrations and for different periods of time. Staining with a fluorescence-labeled anti-epithelial antibody detects both vital and dying tumor cells, distinguishing vital from dying cells through membrane permeability and nuclear staining with propidium iodide. Increasing percentages of dying tumor cells are observed dependent on time and concentration. The sensitivity can vary during therapy and was correlated with decrease or increase in CETC and clinical outcome. Conclusions/Significance: Thus, we are able to show that chemosensitivity testing of circulating tumor cells provides real-time information about the sensitivity of the tumor present in the patient, even at different times during therapy, and correlates with treatment success.

Pregnancy and Childbirth After Sertoli-Leydig Cell Tumor Resection:A Case Study and Literature Review

Objectives:To explore the clinical manifestations and pathological features in the biopsy of ovarian Sertoli-Leydig cell tumor,as well as to improve the clinical understanding of the disease.Methods:A case of pregnancy and childbirth after Sertoli-Leydig cell tumor resection was retrospectively analyzed.The patients’clinical data were collected,including the clinical manifestations,postoperative biopsy results,auxiliary examination results,immunohistochemical results,treatment,and prognosis of the patient.Results:(1)SLCT occurred unilaterally;(2)according to the International Federation of Obstetrics and Gynecology(FIGO),the clinical staging was stage IA;according to the pathological classification of malignant tumors,it was gradeⅡ(moderately differentiated);(3)a healthy female live baby was delivered.Conclusion:Such tumors are rare low-grade malignancies and are even rarer in pregnancy.An increase in preoperative testosterone levels with positive ultrasonography results can be used to assist diagnosis;however,postoperative biopsy pathology remains the“gold standard”for the diagnosis of SLCTs.The definite diagnosis of SLCTs is of great significance for surgical planning and prognostic evaluation.

Expression of MTA2 Gene in Ovarian Epithelial Cancer and Its Clinical Implication

In order to investigate the roles of MTA2 in the pathogenesis of ovarian epithelial cancer, the expression of MTA2 in 4 ovarian cell lines were detected by semi-quantitative RT-PCR and Western-blot assays. MTA2 expression in normal, borderline, benign and malignant epithelial ovarian tissues was immunohistochemically examined. The expression of MTA2 mRNA and protein was detected in all of 4 cell lines of ovarian epithelial cancer. The expression of MTA2 mRNA and protein was higher in strong migration cell lines than in weak migration ones. In borderline and ma lignant ovarian tissues tested, MTA2 staining was dramatically stronger than in normal and benign tissues （P〈0. 01）. The expression levels in malignant ovarian tissues were significantly higher than that in borderline epithelial ovarian tissues （P〈0.01）. The expression of MTA2 was correlated with clinical stage, histopathological grade and lymph node metastasis. It was concluded that the high expression of MTA2 was associated with more aggressive behaviors of epithelial ovarian cancer. MTA2 provides a novel indicator of ovarian cancer.

Establishment of an optimized CTC detection model consisting of EpCAM,MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics

Objective:Emerging studies have demonstrated the promising clinical value of circulating tumor cells(CTCs)for diagnosis,disease assessment,treatment monitoring and prognosis in epithelial ovarian cancer.However,the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common standards.Methods:We enrolled 160 patients with epithelial ovarian cancer as the experimental group,and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control group.We enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens(EpCAM and MUC1),and used multiple reverse transcription-polymerase chain reaction(RT-PCR)detecting three markers(EpCAM,MUC1 and WT1)for quantification.And then we used a binary logistic regression analysis and focused on EpCAM,MUC1 and WT1 to establish an optimized CTC detection model.Results:The sensitivity and specificity of the optimized model is 79.4%and 92.2%,respectively.The specificity of the CTC detection model is significantly higher than CA125(92.2%vs.82.2%,P=0.044),and the detection rate of CTCs was higher than the positive rate of CA125(74.5%vs.58.2%,P=0.069)in early-stage patients(stage I and II).The detection rate of CTCs was significantly higher in patients with ascitic volume≥500 mL,suboptimal cytoreductive surgery and elevated serum CA125 level after 2 courses of chemotherapy(P<0.05).The detection rate of CTC;and CTC;was significantly higher in chemo-resistant patients(26.3%vs.11.9%;26.4%vs.13.4%,P<0.05).The median progression-free survival time for CTC;patients trended to be longer than CTC;patients,and overall survival was shorter in CTC;patients(P=0.043).Conclusions:Our study presents an optimized detection model for CTCs,which consists of the expression levels of three markers(EpCAM,MUC1 and WT1).In comparison with CA125,our model has high specificity and demonstrates better diagnostic values,especially for early-stage ovarian cancer.Detection of CTC;and CTC;had predictive value for chemotherapy resistance,and the detection of CTC;suggested poor prognosis.

Relationship between phenotypes of cell-function differentiation and pathobiological behavior of gastric carcinomas

AIM: To reveal the correlation between the functional differentiation phenotypes of gastric carcinoma cells and the invasion and metastasis by a new way of cell-function classification.METHODS:Surgically resected specimens of 361 gastric carcinomas(GC) were investigated with enzyme-, mucin-, and tumor-related marker immunohistochemistry. According to the direction of cell-function differentiation, stomach carcinomas were divided into five functionally differentiated types. RESULTS: (1) Absorptive function differentiation type (AFDT): there were 82 (22.7%) patients including 76 (92.7%) aged 45 years. Sixty-nine (84.1%) cases belonged to the intestinal type. Thirty-eight (46.3%) expressed CD44v6 and 9 (13.6%) of 66 male patients developed liver metastasis.The 5-year survival rate of patients in this group (58.5%) was higher than those with the other types (P【0.01). (2) Mucin secreting function differentiation type (MSFDT): 54 (15%) cases. Fifty-three (98.1%) tumors had penetrated the serosa, 12 (22.2%) expressed ER and 22 (40.7%) expressed CD44v6. The postoperative 5-year survival rate was 28.6%. (3) Absorptive and mucin-producing function differentiation type (AMPFDT): there were 180 (49.9%) cases, including 31 (17.2%) aged younger than 45 years. The tumor was more common in women (62, 34.4%,) and expressed more frequently estrogen receptors (ER) (129, 81.7%) than other types (P【0.01). Ovary metastasis was found in 12 (19.4%) out of 62 female subjects. The patients with this type GC had the lowest 5-year survival rate (24.7%) among all types. (4) Specific function differentiation type (SFDT): 13 (3.6%) cases. Nine (69.2%) tumors of this type derived from APUD system, the other 4 (30.7%) were of different histological differentiation. Sixty per cent of the patients survived at least five years. (5) Non-function differentiation type (NFDT): 32 (8.9%) cases. Nineteen (59.4%) cases had lymph node metastases but no one with liver or ovary metastasis. The 5-year survival rate was 28.1%. CONCLUSION: This new cell-function classification of GC is helpful in indicating the characteristics of invasion and metastasis of GC with different cell-function differentiation phenotypes. Further study is needed to disclose the correlation between the cell-functional differentiation phenotypes and the relevant genotypes and the biological behavior of gastric carcinoma.