ABSTRACT
BACKGROUND: Circulating epithelioid cells (CECs), also known as circulating tumor, circulating cancer, circulating epithelial, or circulating nonhematologic cells, are a prognostic factor in various malignancies that can be isolated via various protocols. In the current study, the authors analyzed the cytomorphologic characteristics of CECs isolated by size in a cohort of patients with benign and malignant pancreatic diseases to determine whether cytomorphological features could predict CEC origin. METHODS: Blood samples were collected from 9 healthy controls and 171 patients with pancreatic disease who were presenting for surgical evaluation before treatment. Blood was processed with the ScreenCell size-based filtration device. Evaluable CECs were analyzed in a blinded fashion for cytomorphologic characteristics, including cellularity; nucleoli; nuclear size, irregularity, variability, and hyperchromasia; and nuclear-to-cytoplasmic ratio. Statistical differences between variables were analyzed via the Fisher exact test. RESULTS: No CECs were identified among the 9 normal healthy controls. Of the 115 patients with CECs (positive or suspicious for), 25 had nonmalignant disease and 90 had malignancy. There were no significant differences in any of the cytologic criteria noted between groups divided by benign versus malignant, neoplastic versus nonneoplastic, or pancreatic ductal adenocarcinoma versus neuroendocrine tumor. CONCLUSIONS: CECs were observed in patients with malignant and nonmalignant pancreatic disease, but not in healthy controls. There were no morphologic differences observed between cells from different pancreatic diseases, suggesting that numerous conditions may be associated with CECs in the circulation and that care must be taken not to overinterpret cells identified by cytomorphology as indicative of circulating tumor cells of pancreatic cancer. Additional studies are required to determine the origin and clinical significance of these cells. Cancer Cytopathol 2017;125:332-340. © 2017 American Cancer Society.
Subject(s)
Adenocarcinoma/pathology , Adenoma/pathology , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/pathology , Common Bile Duct Neoplasms/pathology , Neoplasms, Cystic, Mucinous, and Serous/pathology , Neoplastic Cells, Circulating/pathology , Pancreatic Neoplasms/pathology , Adenocarcinoma/blood , Adenoma/blood , Ampulla of Vater/pathology , Bile Duct Neoplasms/blood , Carcinoma, Acinar Cell/blood , Carcinoma, Acinar Cell/pathology , Carcinoma, Pancreatic Ductal/blood , Carcinoma, Pancreatic Ductal/pathology , Case-Control Studies , Cholangiocarcinoma/blood , Common Bile Duct Neoplasms/blood , Cystadenoma, Serous/blood , Cystadenoma, Serous/pathology , Epidermal Cyst , Humans , Neoplasms, Cystic, Mucinous, and Serous/blood , Neuroendocrine Tumors/blood , Neuroendocrine Tumors/pathology , Pancreatic Diseases/blood , Pancreatic Diseases/pathology , Pancreatic Neoplasms/blood , Pancreatitis, Chronic/blood , Pancreatitis, Chronic/pathology , Prognosis , Splenic DiseasesABSTRACT
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 Dumlupinar 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.
Subject(s)
Cystadenoma, Serous/blood , Cystadenoma, Serous/diagnostic imaging , Ovarian Neoplasms/blood , Ovarian Neoplasms/diagnostic imaging , Adult , Aged , CA-125 Antigen/metabolism , Cystadenoma, Serous/metabolism , Female , Humans , Leukocyte Count , Lymphocyte Count , Membrane Proteins/metabolism , Middle Aged , Neutrophils/cytology , Ovarian Neoplasms/metabolism , Platelet Count , Preoperative Period , Retrospective Studies , UltrasonographySubject(s)
Cystadenoma, Papillary/diagnostic imaging , Cystadenoma, Serous/diagnostic imaging , Cystadenoma, Serous/secondary , Image Enhancement , Magnetic Resonance Imaging , Ovarian Neoplasms/diagnostic imaging , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/secondary , Carcinoembryonic Antigen/blood , Contrast Media , Cystadenoma, Papillary/blood , Cystadenoma, Serous/blood , Diagnosis, Differential , Female , Humans , Meglumine , Middle Aged , Organometallic Compounds , Ovarian Neoplasms/blood , Peritoneal Neoplasms/blood , Rupture, SpontaneousABSTRACT
BACKGROUND AND AIMS: The American Gastroenterological Association (AGA) recently reported evidence-based guidelines for the management of asymptomatic neoplastic pancreatic cysts. These guidelines advocate a higher threshold for surgical resection than prior guidelines and imaging surveillance for a considerable number of patients with pancreatic cysts. The aims of this study were to assess the accuracy of the AGA guidelines in detecting advanced neoplasia and present an alternative approach to pancreatic cysts. METHODS: The study population consisted of 225 patients who underwent EUS-guided FNA for pancreatic cysts between January 2014 and May 2015. For each patient, clinical findings, EUS features, cytopathology results, carcinoembryonic antigen analysis, and molecular testing of pancreatic cyst fluid were reviewed. Molecular testing included the assessment of hotspot mutations and deletions for KRAS, GNAS, VHL, TP53, PIK3CA, and PTEN. RESULTS: Diagnostic pathology results were available for 41 patients (18%), with 13 (6%) harboring advanced neoplasia. Among these cases, the AGA guidelines identified advanced neoplasia with 62% sensitivity, 79% specificity, 57% positive predictive value, and 82% negative predictive value. Moreover, the AGA guidelines missed 45% of intraductal papillary mucinous neoplasms with adenocarcinoma or high-grade dysplasia. For cases without confirmatory pathology, 27 of 184 patients (15%) with serous cystadenomas (SCAs) based on EUS findings and/or VHL alterations would continue magnetic resonance imaging (MRI) surveillance. In comparison, a novel algorithmic pathway using molecular testing of pancreatic cyst fluid detected advanced neoplasias with 100% sensitivity, 90% specificity, 79% positive predictive value, and 100% negative predictive value. CONCLUSIONS: The AGA guidelines were inaccurate in detecting pancreatic cysts with advanced neoplasia. Furthermore, because the AGA guidelines manage all neoplastic cysts similarly, patients with SCAs will continue to undergo unnecessary MRI surveillance. The results of an alternative approach with integrative molecular testing are encouraging but require further validation.
Subject(s)
Carcinoma, Pancreatic Ductal/diagnosis , Neoplasms, Cystic, Mucinous, and Serous/diagnosis , Pancreatic Cyst/diagnosis , Pancreatic Neoplasms/diagnosis , Practice Guidelines as Topic , Adenocarcinoma/blood , Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoembryonic Antigen/blood , Carcinoma, Pancreatic Ductal/blood , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Chromogranins/genetics , Class I Phosphatidylinositol 3-Kinases , Cyst Fluid , Cystadenoma, Serous/blood , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/genetics , Cystadenoma, Serous/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Endosonography , Female , GTP-Binding Protein alpha Subunits, Gs/genetics , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Molecular Diagnostic Techniques , Neoplasms, Cystic, Mucinous, and Serous/blood , Neoplasms, Cystic, Mucinous, and Serous/genetics , Neoplasms, Cystic, Mucinous, and Serous/pathology , PTEN Phosphohydrolase/genetics , Pancreatic Cyst/blood , Pancreatic Cyst/genetics , Pancreatic Cyst/pathology , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Retrospective Studies , Sensitivity and Specificity , Tumor Suppressor Protein p53/genetics , Von Hippel-Lindau Tumor Suppressor Protein/genetics , Young AdultABSTRACT
OBJECTIVE: Serous ovarian carcinoma (OC) represents a leading cause of cancer-related death among U.S. women. Non-invasive tools have recently emerged for discriminating benign from malignant ovarian masses, but evaluation remains ongoing, without widespread implementation. In the last decade, metabolomics has matured into a new avenue for cancer biomarker development. Here, we sought to identify novel plasma metabolite biomarkers to distinguish serous ovarian carcinoma and benign serous ovarian tumor. METHODS: Using liquid chromatography-mass spectrometry, we conducted global and targeted metabolite profiling of plasma isolated at the time of surgery from 50 serous OC cases and 50 serous benign controls. RESULTS: Global lipidomics analysis identified 34 metabolites (of 372 assessed) differing significantly (P<0.05) between cases and controls in both training and testing sets, with 17 candidates satisfying FDR q<0.05, and two reaching Bonferroni significance. Targeted profiling of ~150 aqueous metabolites identified a single amino acid, alanine, as differentially abundant (P<0.05). A multivariate classification model built using the top four lipid metabolites achieved an estimated AUC of 0.85 (SD=0.07) based on Monte Carlo cross validation. Evaluation of a hybrid model incorporating both CA125 and lipid metabolites was suggestive of increased classification accuracy (AUC=0.91, SD=0.05) relative to CA125 alone (AUC=0.87, SD=0.07), particularly at high fixed levels of sensitivity, without reaching significance. CONCLUSIONS: Our results provide insight into metabolic changes potentially correlated with the presence of serous OC versus benign ovarian tumor and suggest that plasma metabolites may help differentiate these two conditions.
Subject(s)
Biomarkers, Tumor/blood , Cystadenocarcinoma, Serous/blood , Cystadenoma, Serous/blood , Lipids/blood , Ovarian Diseases/blood , Ovarian Neoplasms/blood , Aged , CA-125 Antigen/blood , Case-Control Studies , Chromatography, Liquid , Female , Humans , Mass Spectrometry , Membrane Proteins/blood , Middle AgedABSTRACT
PURPOSE: Ovarian cancer is the fourth cause of death from cancer in women worldwide and the majority of its diagnoses is made in an advanced stage of the disease. Several sonographic scoring systems have been created for a better preoperative discrimination between benign and malignant pelvic masses. The aim of this study was to evaluate the performances of the Risk of the Malignancy Index 3 (RMI 3) and the Pelvic Masses Score (PMS). MATERIALS AND METHODS: This retrospective study was performed in 55 women admitted to the department of Obstetrics and Gynecology of University of Udine for surgical exploration of pelvic masses between 2009 and 2012. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for both the scores. RESULTS: PMS showed a sensitivity of 100%, a specificity of 93.8%, a PPV of 70%, and a NPV of 100%, while RMI 3 yielded a sensitivity of 85%, a specificity of 91%, a PPV of 60%, and a NPV of 97.8%. CONCLUSION: The authors found that, in discriminating between benign and malignant pelvic disease, the PMS method was more reliable than RMI3. PMS is a simple scoring system which can be used in clinical practice.
Subject(s)
Carcinoma, Endometrioid/diagnostic imaging , Cystadenocarcinoma, Serous/diagnostic imaging , Cystadenoma, Mucinous/diagnostic imaging , Cystadenoma, Serous/diagnostic imaging , Ovarian Cysts/diagnostic imaging , Ovarian Neoplasms/diagnostic imaging , Teratoma/diagnostic imaging , Adult , Aged , Aged, 80 and over , CA-125 Antigen/blood , Carcinoma, Endometrioid/blood , Carcinoma, Endometrioid/pathology , Cystadenocarcinoma, Serous/blood , Cystadenocarcinoma, Serous/pathology , Cystadenoma, Mucinous/blood , Cystadenoma, Mucinous/pathology , Cystadenoma, Serous/blood , Cystadenoma, Serous/pathology , Female , Humans , Membrane Proteins/blood , Middle Aged , Ovarian Cysts/blood , Ovarian Cysts/pathology , Ovarian Neoplasms/blood , Ovarian Neoplasms/pathology , Predictive Value of Tests , ROC Curve , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Teratoma/blood , Teratoma/pathology , Ultrasonography , Young AdultABSTRACT
The purpose of this work was the assessment of cytotoxic reaction mediators - granzymes A and B in the serum of women with ovarian tumors. The study included 120 women with proven ovarian tumors. The control group consisted of 60 healthy women in whom no pathological changes within the reproductive system were detected. Concentrations of granzymes A and B were measured by enzyme-linked immunosorbent (ELISA) assay. The highest concentrations of the studied parameters were observed in serum of women with ovarian cancer. Moreover, the concentrations of granzymes A and B in patients with ovarian cancer were substantially increased in comparison to concentrations in patients with ovarian cystadenomas (P < 0.0001) or ovarian teratomas (P < 0.0001).
Subject(s)
Cystadenocarcinoma, Serous/blood , Cystadenoma, Serous/blood , Granzymes/blood , Neoplasm Proteins/blood , Ovarian Neoplasms/blood , Teratoma/blood , Adult , Apoptosis , CA-125 Antigen/blood , Case-Control Studies , Cystadenocarcinoma, Serous/immunology , Cystadenoma, Serous/immunology , Cytotoxicity, Immunologic , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lymphocytes, Tumor-Infiltrating/enzymology , Lymphocytes, Tumor-Infiltrating/immunology , Menopause/blood , Menstrual Cycle/blood , Middle Aged , Ovarian Neoplasms/immunology , Teratoma/immunology , Young AdultABSTRACT
The serum N-glycome is a promising source of biomarker discovery. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) profiling of serum N-glycans was attempted for differentiating borderline ovarian tumor from benign cases, for which a low data spread is essential. An experimental protocol using matrix-prespotted MALDI plates and fast vacuum drying of the loaded N-glycan samples was developed, thereby minimizing the intensity variations in the replicates to an average relative standard deviation (RSD) of 3.96% for the highest N-glycan peak (m/z 1485.53) of the Sigma-Aldrich serum standard. When applied to sera of ovarian tumors, this procedure exhibited an average RSD of 5.74% for m/z 1485.53 and of 7.28% for all MS peaks. This improved reproducibility combined with the OVA-Beyond(®) screening software resulted in 75.1% and 79.4% correct classification for benign and borderline tumor samples, respectively, while the classification rates by the conventional ovarian tumor marker CA-125 were 54.4% and 53.1%, respectively. Both true positive rate and true negative rate fluctuated with small numbers of markers and converged as the number of markers increased. Cross-validations were performed in comparison with CA-125. These results suggest that our optimized process for MALDI-TOF MS of the serum glycome has a great potential for the screening of early stage ovarian cancer.
Subject(s)
Biomarkers, Tumor/blood , Cystadenoma, Mucinous/blood , Cystadenoma, Serous/blood , Ovarian Neoplasms/blood , Polysaccharides/blood , Teratoma/blood , Adult , CA-125 Antigen/blood , Cystadenoma, Mucinous/diagnosis , Cystadenoma, Serous/diagnosis , Diagnosis, Differential , Endometriosis/blood , Endometriosis/diagnosis , Female , Humans , Middle Aged , Ovarian Neoplasms/diagnosis , Reproducibility of Results , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Teratoma/diagnosisABSTRACT
PURPOSE: To evaluate human epididymis protein 4 (HE4) as an extrabiomarker to cancer antigen 125 (CA125) to improve the detection of ovarian carcinoma. METHODS: Sixty patients with ovarian carcinoma, 50 patients with benign ovarian tumors and 30 healthy women were included in the present study. Serum concentration of HE4 was assayed using ELISA technique, while CA125 was assayed using chemiluminescent enzyme immunoassay. RESULTS: The median CA125 and HE4 serum values were significantly higher among ovarian cancer patients when compared with healthy control However, the median serum levels of CA125 but not HE4 were significantly higher among patients with benign ovarian tumors as compared to healthy women. Based on the receiver operator characteristics curve analysis, HE4 had higher sensitivities than CA125 for the detection of ovarian cancer at 90, 95 and 98 % specificities and the combination of both markers yielded a higher sensitivity than either alone. However, CA125 but not HE4 had higher sensitivities for the detection of benign ovarian tumors at the same specificities. In addition, a positive correlation was observed between HE4 and CA125 among patients with ovarian carcinoma. CONCLUSION: HE4 is a valuable marker for ovarian cancer diagnosis and when combined with CA125, they had a higher sensitivity at a set specificity, thus providing a more accurate predictor of ovarian cancer than either alone.
Subject(s)
Biomarkers, Tumor/blood , CA-125 Antigen/blood , Carcinoma/blood , Cystadenoma, Serous/blood , Ovarian Neoplasms/blood , Proteins/metabolism , Adult , Area Under Curve , Carcinoma/diagnosis , Case-Control Studies , Double-Blind Method , Endometriosis/blood , Female , Humans , Middle Aged , Ovarian Neoplasms/pathology , ROC Curve , WAP Four-Disulfide Core Domain Protein 2 , Young AdultABSTRACT
The aim of the study was to examine the concentrations of the soluble receptors and their ligands of CD30/CD30L and CD40/CD40L systems in the serum of women with ovarian tumor and in the ovarian cyst fluid of women with Cystadenoma serosum. The study included 120 women with ovarian tumors. As a control, sera were obtained from 60 healthy female volunteers. Concentrations of the sCD30, sCD30L, sCD40 and sCD40L in the serum and the ovarian cyst fluid were measured by ELISA enzyme-linked immunosorbent assay. Concentrations of both sCD30 and sCD30L in serum of women with ovarian tumors were significantly higher than in control (p < 0.0001). The highest serum receptor and its ligand levels were observed in women with ovarian cancer (p < 0.0001). Moreover, results showed significantly increased levels of sCD40 and sCD40L serum in women with ovarian tumors, as compared to the control group (p < 0.0001). The highest concentration of sCD40 in the serum of women with ovarian cancer and sCD40L in serum of women with Teratoma maturum (p < 0.0001) were observed. Impaired apoptosis among women with ovarian tumors is associated with the impairments of soluble CD30/CD30L and CD40/CD40L systems. Measurement of studied parameter concentrations in serum of women with ovarian tumors has been suggested to be a potential tool in monitoring of inflammatory. Evaluation of sCD30, sCD30L and sCD40 might be an early diagnostic marker in patients with the ovarian cancer. Concentrations of the studied parameters in the ovarian cyst fluid higher than the serum values suggest local suppression of the immune response. However, the final evaluation of the importance of measurement of serum levels of them requires further investigation.
Subject(s)
CD30 Ligand/blood , CD40 Antigens/blood , CD40 Ligand/blood , Cystadenocarcinoma, Serous/blood , Cystadenoma, Serous/blood , Ki-1 Antigen/blood , Ovarian Neoplasms/blood , Teratoma/blood , Adult , Case-Control Studies , Cystadenocarcinoma, Serous/diagnosis , Cystadenoma, Serous/diagnosis , Female , Humans , Middle Aged , Ovarian Cysts/chemistry , Ovarian Neoplasms/diagnosis , Solubility , Teratoma/diagnosisABSTRACT
BACKGROUND AND OBJECTIVE: Erythropoietin (Epo) is a glycoprotein that stimulates proliferation and migration of human endothelial cells and promotes angiogenesis, which are crucial phenomena in cancer biology. The objective of this study was to investigate whether Epo is detectable in the ascitic fluid of patients with ovarian tumors. PATIENTS AND METHODS: We investigated the presence of Epo in the ascitic fluid of 100 women undergoing laparotomy for an ovarian tumor. Epo concentration was quantitated with an immunochemiluminometric assay. RESULTS: Ten women had a benign tumor, 13 women had a borderline tumor, and 77 women had ovarian cancer. Epo was detected in all ascitic fluid samples, in similar amounts as in corresponding serum samples. Ascitic fluid Epo concentration did not differ between the 3 study groups (P = 0.081), but in multiple comparisons, ascitic fluid Epo was higher in the women with cancer than in the women with a benign tumor (P = 0.006). Ascitic fluid Epo concentration correlated positively with serum Epo (P < 0.0001) and the volume of ascites (P < 0.0001). In regression analyses, serum Epo, volume of ascites, blood hemoglobin, plasma CA125, tumor stage, tumor grade, and the presence of residual tumor after surgery had no significant independent effect on ascitic fluid Epo. CONCLUSION: Considerable amounts of Epo are present in the ascitic fluid of women with ovarian tumors. The origin of Epo in the ascitic fluid of women with ovarian tumors as well as the clinical relevance of our finding remain to be clarified.
Subject(s)
Ascitic Fluid/chemistry , Erythropoietin/isolation & purification , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Ascitic Fluid/pathology , Biomarkers, Tumor/isolation & purification , Biomarkers, Tumor/metabolism , CA-125 Antigen/blood , Carcinoma, Ovarian Epithelial , Cystadenoma, Serous/blood , Cystadenoma, Serous/metabolism , Cystadenoma, Serous/pathology , Erythropoietin/blood , Erythropoietin/metabolism , Female , Hemoglobins/analysis , Humans , Membrane Proteins/blood , Neoplasms, Glandular and Epithelial/blood , Neoplasms, Glandular and Epithelial/metabolism , Osmolar Concentration , Ovarian Cysts/blood , Ovarian Cysts/metabolism , Ovarian Cysts/pathology , Ovarian Neoplasms/blood , Ovarian Neoplasms/metabolismABSTRACT
OBJECTIVE: To investigate the clinical value of combination of human epididymis protein 4 (HE4), CA125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in diagnosis of ovarian carcinoma. METHODS: To detect the serum concentration of HE4 using ELISA and CA125 using ECL in patients of ovarian carcinoma group (n = 119), borderline ovarian tumor group (n = 36), benign ovarian neoplasm group (n = 96) and female healthy control group (n = 53). The ROMA based on the serum level of CA125, HE4 and a woman's menopausal status was used to calculate the predicted probability (PP) and diagnostic results of ovarian cancers. RESULTS: The receiver operating characteristic (ROC) analysis showed the cut-off value was 67.3 pmol/L (the AUC was 0.906, the sensitivity was 80.7% and specificity was 94.6%). The serum levels of HE4 and CA125 in the ovarian carcinoma group were significantly higher than that in the borderline ovarian tumor group, benign ovarian neoplasm group and female healthy control group (P < 0.01). The serum levels of CA125 and HE4 showed statistically no significant difference between the borderline ovarian tumor group and benign ovarian neoplasm group (P > 0.05). The levels of HE4 and CA125 were reduced significantly in ovarian patients after surgery therapy (P < 0.01). The sensitivity and specificity of HE4 + CA125 combination was 92.7% and 72.5%. The ROMA that can classify patients into high and low risk groups was established as 9.3% in premenopausal and 27.3% in postmenopausal women. CONCLUSIONS: HE4 is a helpful biomarker for ovarian carcinoma diagnosis. Biomarker combination of HE4 and CA125, and applying of the ROMA are helpful to improve the accuracy in diagnosis of ovarian cancers.
Subject(s)
CA-125 Antigen/blood , Cystadenocarcinoma, Serous/diagnosis , Ovarian Neoplasms/diagnosis , Proteins/metabolism , Adenocarcinoma, Mucinous/blood , Adenocarcinoma, Mucinous/diagnosis , Adenocarcinoma, Mucinous/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Cystadenocarcinoma, Serous/blood , Cystadenocarcinoma, Serous/surgery , Cystadenoma, Serous/blood , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/surgery , Endometriosis/blood , Endometriosis/diagnosis , Female , Humans , Menopause , Middle Aged , Ovarian Neoplasms/blood , Ovarian Neoplasms/surgery , ROC Curve , Sensitivity and Specificity , Teratoma/blood , Teratoma/diagnosis , Teratoma/surgery , WAP Four-Disulfide Core Domain Protein 2 , Young AdultABSTRACT
INTRODUCTION: Ovarian cancer is associated with high mortality due to presentation at advanced stage and high recurrence following treatment with chemotherapy. Most of the prognostic variables in ovarian cancer, including stage and residual disease, are amenable for assessment only after surgery. Currently there are no established preoperative markers including, CA-125, that can predict overall survival in patients with ovarian cancer. The aim of our study was to evaluate the prognostic significance of the preoperative haematological markers platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) in patients with ovarian cancer. METHOD: Preoperative PLR and NLR were evaluated in 235 patients undergoing surgery for ovarian cancer. The prognostic significance of both markers was then determined by both uni- and multivariate analytical methods. RESULTS: High preoperative PLR (p < 0.001) and NLR (p = 0.001) were significantly associated with poor survival using univariate Cox survival analysis. The median overall survival in patients with a PLR of < 300 was 37.4 months (95% CI 26.1-48.7) and 14.5 months (95% CI 11.7-17.2) in those with a PLR of > 300. PLR (p = 0.03) but not NLR (p = 0.575) retained its significance as a prognostic marker on multivariate Cox's regression analysis, along with stage (p < 0.001) and residual disease (p = 0.015). CONCLUSION: We have shown for the first time that PLR is a novel independent prognostic marker in patients with ovarian cancer (AU)
Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Adenocarcinoma, Clear Cell , Adenocarcinoma, Mucinous/diagnosis , Ovarian Neoplasms/blood , Ovarian Neoplasms/surgery , Cystadenoma, Serous/diagnosis , Endometrial Neoplasms/diagnosis , Lymphocytes/pathology , Ovarian Neoplasms/diagnosis , Platelet Count , Biomarkers, Tumor , Adenocarcinoma, Clear Cell/blood , Adenocarcinoma, Clear Cell/surgery , Adenocarcinoma, Mucinous/blood , Adenocarcinoma, Mucinous/surgery , Cystadenoma, Serous/blood , Cystadenoma, Serous/surgery , Endometrial Neoplasms/blood , Endometrial Neoplasms/surgery , Retrospective StudiesABSTRACT
This study was undertaken to evaluate RANTES levels in the peritoneal fluid (PF) and plasma of patients with ovarian cancer (n=73), serous cystadenoma (n=32) or normal controls (n=9). RANTES levels were correlated to myeloid and lymphoid dendritic cells (DCs). RANTES levels were evaluated using the ELISA assay. DCs were quantified using flow cytometry. The PF and plasma RANTES concentrations were elevated in the ovarian cancer (OVC) patients when compared to the patients with benign tumor (the reference group). Plasma levels of RANTES were higher in OVC patients compared with the reference group and with the controls. There were no significant differences in the plasma RANTES levels based on tumor stage, grade or histology. Women with serous cystadenocarcinoma, clear cell carcinoma and endometrioid cystadenocarcinoma had significantly higher PF RANTES levels than patients with undifferentiated carcinoma. Women with clear cell carcinoma and patients with endometrioid cystadenocarcinoma had higher PF RANTES levels than women with mucinous cystadenocarcinoma. We concluded that RANTES production in the peritoneal cavities of OVC patients depends on the histological type of the tumor cells.
Subject(s)
Ascitic Fluid/metabolism , Chemokine CCL5/metabolism , Cystadenoma, Serous/metabolism , Dendritic Cells/metabolism , Ovarian Neoplasms/metabolism , Chemokine CCL5/blood , Cystadenoma, Serous/blood , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Humans , Ovarian Neoplasms/blood , Statistics, NonparametricABSTRACT
OBJECTIVES: Impairments of apoptosis processes are the basis of pathogenesis of many diseases, including ovarian tumors. The aim of the study was to evaluated the concentration of soluble ligand for receptor CD30 (sCD30L)--marker of apoptosis in women with ovarian tumor. MATERIAL AND METHODS: The study comprised 80 women, aged from 21 to 62, and included 30 patients with Cystadenocarcinoma serosum la, 35 with Cystadenoma serosum and 15 women with Teratoma maturum. The control group consisted of 30 healthy women, aged 24 to 57, with no evidence of pathological disorders in the reproductive system. The concentration of sCD30L in the serum of all studied women and in the fluid of ovarian cyst of women with cystadenoma serous were measured by immunoenzymatic method ELISA. RESULTS: The highest level of sCD30L was observed in the serum of women with ovarian cancer and it was significantly higher when compared to the concentration in the serum of women with cystadenoma serous and teratoma maturum of the ovary (p < 0.0001). In the fluid of ovarian cyst, the concentration of this marker was significantly higher in comparison with the level in the serum (p < 0.0001). CONCLUSIONS: In women with ovarian tumors we observed impairments of the apoptosis process, which is associated with an increased concentration of sCD30L in the serum. These changes are more intense in women with ovarian cancer. Higher level of the study parameter in the fluid of ovarian cyst is associated with the local immune response suppression.
Subject(s)
Apoptosis , Biomarkers, Tumor/blood , Cystadenocarcinoma, Serous/immunology , Cystadenoma, Serous/immunology , Ki-1 Antigen/blood , Ovarian Neoplasms/immunology , Teratoma/immunology , Adult , Aged , Case-Control Studies , Cystadenocarcinoma, Serous/blood , Cystadenoma, Serous/blood , Female , Humans , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/blood , Teratoma/bloodABSTRACT
OBJECTIVE: A number of serum tumor markers have been investigated to aid clinicians in the differential diagnosis of ovarian masses. Serum C-reactive protein (CRP) is a widely used biomarker of inflammation and has been previously shown to be a promising biomarker in patients with ovarian cancer. STUDY DESIGN: In a retrospective single-center study, we evaluated serum CRP in 576 patients with benign and in 242 patients with malignant (ovarian tumors of low malignant potential [LMP]: n=44, epithelial ovarian cancer [EOC]: n=198) ovarian masses. Results were correlated to clinical data. RESULTS: Median (25th, 75th percentiles) serum CRP in patients with benign ovarian tumors, with ovarian tumors of LMP, and with EOC were 0.5 (0.5, 0.6)mg/dL, 0.5 (0.5, 0.9)mg/dL, and 1.36 (0.5, 4.9)mg/dL, respectively (p<0.001). In the subgroup of patients with EOC, serum CRP significantly correlated with FIGO stage (p<0.001), residual tumor mass (p<0.001), and patients' age (p=0.04), but not with tumor grade (p=0.2) and histologic type (p=0.4). In univariable and multivariable models including serum CRP, serum CA 125, and patients' age, serum CRP independently predicted the presence of malignant ovarian masses (p<0.0001; Odds Ratio [OR] 5.3, 95% Confidence Interval [CI] 3.8-7.4). Serum CRP had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying malignant ovarian masses of 49.8%, 84.1%, 57.1%, and 79.8%, respectively. CONCLUSION: Serum CRP is associated with the presence of malignant ovarian tumors independent of serum CA 125 and patients' age and can therefore be used as additional diagnostic marker in the differential diagnosis of ovarian masses.
Subject(s)
Biomarkers, Tumor/blood , C-Reactive Protein/metabolism , Ovarian Diseases/blood , Ovarian Diseases/diagnosis , Ovarian Neoplasms/blood , Ovarian Neoplasms/diagnosis , Adult , Aged , CA-125 Antigen/blood , Cystadenoma, Mucinous/blood , Cystadenoma, Mucinous/diagnosis , Cystadenoma, Serous/blood , Cystadenoma, Serous/diagnosis , Diagnosis, Differential , Endometriosis/blood , Endometriosis/diagnosis , Female , Humans , Middle Aged , Ovarian Cysts/blood , Ovarian Cysts/diagnosis , Predictive Value of Tests , Retrospective Studies , Sensitivity and SpecificityABSTRACT
PURPOSE: This is a review of our 18-year experience with premenarchal girls with epithelial ovarian tumors. Special attention was focused on the predictive value of CA125 serum levels. METHODS: Analysis of premenarchal patients with resected or biopsied ovarian masses from 1988 to 2005 was performed. Patient age, clinical presentation, operative procedures, histologic type of tumor, treatment and outcome were obtained. RESULTS: Six premenarchal girls (aged from 6 to 14 years) were surgically treated for epithelial tumors, representing 13% of all ovarian tumors at this age. Histological findings revealed cystadenoma in four girls, one with a mucinous borderline tumor and one with undifferentiated carcinoma. Tumor volume was higher than 400 cm3 in four girls. Sensitivity, specificity and positive predictive value of CA125 level for ovarian malignant epithelial tumors were 0.50, 0.50, and 0.33, respectively. The premenarchal girl with undifferentiated carcinoma in Stage III died after six months in spite of chemotherapy. CONCLUSION: Ovarian epithelial tumors in premenarchal girls show important growth potential and a relatively high malignancy rate with great influence of borderline neoplasms. CA125 is a tumor marker with low sensitivity and specificity for detection of epithelial ovarian malignancy in this age group.
Subject(s)
CA-125 Antigen/blood , Carcinoma/blood , Cystadenocarcinoma, Mucinous/diagnosis , Cystadenoma, Serous/diagnosis , Ovarian Neoplasms/blood , Adolescent , Biomarkers, Tumor/blood , Carcinoma/pathology , Child , Cystadenocarcinoma, Mucinous/blood , Cystadenoma, Serous/blood , Female , Humans , Menarche , Neoplasm Staging , Ovarian Neoplasms/pathology , Predictive Value of Tests , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
An isoenzyme of pyruvate kinase (Tu M2-PK) is overexpressed by tumor cells and can be measured in blood by a specific immunoenzymatic assay. Our objective was to investigate the diagnostic value of Tu M2-PK in comparison with that of CA 19-9 in pancreatic cancer. We studied 265 subjects: 60 with histologically confirmed pancreatic cancer, 43 with benign pancreatic diseases (acute and chronic pancreatitis), 5 with benign cystic neoplasms of the pancreas, 9 with neuroendocrine tumors, 77 with other abdominal malignancies, 47 with benign digestive diseases, and 24 healthy controls. Levels of plasma Tu M2-PK and serum CA 19-9 were determined by commercially available specific immunoassays. The diagnostic sensitivity and specificity of Tu M2-PK for pancreatic cancer were 85 and 41%, respectively, while those of CA 19-9 were 75 and 81%. The combination of the two tests significantly increased sensitivity (97%) but lowered specificity (38%). In discriminating between pancreatic cancer and acute or chronic pancreatitis, Tu M2-PK turned out to be less accurate than CA 19-9. In patients without pancreatic tumor, cholestasis appeared not to affect the values of Tu M2-PK, while CA 19-9 was found to be significantly higher. Tu M2-PK was also abnormally high in the majority of patients with other digestive malignancies or neuroendocrine tumors. The results demonstrate that Tu M2-PK has a satisfactory sensitivity but a poor specificity in the diagnosis of pancreatic cancer. Used together with CA 19-9, the sensitivity increases considerably.
Subject(s)
Biomarkers, Tumor/blood , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/diagnosis , Pyruvate Kinase/blood , Acute Disease , Adult , Aged , Aged, 80 and over , CA-19-9 Antigen/blood , Chronic Disease , Cystadenoma, Serous/blood , Digestive System Diseases/blood , Female , Humans , Male , Middle Aged , Pancreatitis/blood , ROC Curve , Sensitivity and SpecificityABSTRACT
BACKGROUND: Differentiating between mucinous cystic tumors (MCTs) and serous cystic tumors (SCTs) can be a troubling diagnostic dilemma in pancreatology: when SCTs present in their macro-oligocystic form they must be resected because MCT cannot be ruled out, and some tumors considered benign are actually MCTs, which delays diagnosis and places patients at increased risk. Examination of preoperative serum tumor markers may help improve preoperative diagnosis. MATERIALS AND METHODS: The tumor markers CEA, Ca 19-9, Ca 125, and Ca 15-3 were examined in 157 patients with SCTs or MCTs. RESULTS: Positive CEA marker status is an indicator of an MCT, although sensitivity is low at 17%. Using three serum tumor markers (CEA, Ca 19-9, and Ca 125), 27% of MCTs were found to have two or more markers positive, compared to none for the SCTs. Sensitivity decreases to 13% for differentiating benign MCTs from benign SCTs but specificity remains 100%. CONCLUSIONS: In the differential diagnosis of SCTs vs. MCTs no reliable serum tumor marker exists which can diagnose SCTs and spare some patients unnecessary operations. Nonetheless, positive CEA serum marker status and or the presence of more than two positive serum markers (CEA, Ca 19-9, or Ca 125) indicates the presence of an MCT and can prevent delay in diagnosis.