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1.
Histopathology ; 79(2): 252-259, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33657658

ABSTRACT

AIMS: Because serous cystadenoma (SCA) does not usually require excision, it is critical to distinguish it from differential diagnoses which do, especially neuroendocrine tumour (NET). The gold standard for diagnosing SCA is assessment of endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNAB) material. Inhibin immunohistochemistry aids this assessment, but such positivity is not absolutely sensitive or specific to SCA. The following is the largest known study of SCA EUS-FNAB specimens and the first to compare four potential SCA immunomarkers between themselves and inhibin, compared against NET. METHODS AND RESULTS: Immunohistochemistry for calponin, mucin 6 (MUC6), glucose transporter 1 (GLUT1) and vascular endothelial growth factor A (VEGFA) was performed on 30 EUS-FNAB and three resection specimens of SCA and 32 EUS-FNAB specimens of NET. GLUT1 and VEGFA were suboptimal as diagnostic immunomarkers of SCA, being expressed by 10 and 44% of NETs, respectively. Further, their expression by cellular constituents of blood which often contaminate EUS-FNAB specimens hampered identification of neoplastic cells, especially in hypocellular samples. While 19% of NETs showed nuclear MUC6 positivity, cytoplasmic expression of the protein showed 100% specificity and sensitivity as an SCA marker. However, assessing MUC6 in EUS-FNAB specimens must also consider the protein's focal expression in physiological pancreatic, gastric or duodenal tissues, which can contaminate these specimens. Calponin was less sensitive (71% versus 100%) but more specific (100% versus 91%) than inhibin, although easier to assess in EUS-FNAB specimens than MUC6. CONCLUSIONS: Of the four potential immunomarkers of SCA suggested by the existing literature, calponin and MUC6 are useful complementary studies to inhibin for application to EUS-FNAB specimens.


Subject(s)
Calcium-Binding Proteins/metabolism , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/immunology , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Inhibins/metabolism , Microfilament Proteins/metabolism , Mucin-6/metabolism , Adolescent , Adult , Aged , Biomarkers, Tumor , Calcium-Binding Proteins/immunology , Cohort Studies , Cystadenoma, Serous/pathology , Duodenum/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration/instrumentation , Female , Glucose Transporter Type 1/metabolism , Humans , Immunohistochemistry , Inhibins/immunology , Male , Microfilament Proteins/immunology , Middle Aged , Neuroendocrine Tumors/pathology , Pancreas/pathology , Stomach/pathology , Synaptophysin/metabolism , Vascular Endothelial Growth Factor A/metabolism , Calponins
2.
J Am Soc Cytopathol ; 10(3): 249-254, 2021.
Article in English | MEDLINE | ID: mdl-33541830

ABSTRACT

INTRODUCTION: Determining the risk of malignancy in a pancreatic cyst (PC) is a clinical and diagnostic challenge. Monoclonal antibody (mAb) Das-1 test was shown to have high sensitivity, specificity, and accuracy in detecting high-risk (HR) cysts. Das-1 mAb test detects HR mucinous cysts with high-grade dysplasia (HGD), invasive carcinoma, and/or intestinal-type epithelium. Correlation of mAb Das-1 testing of PC fluids with cytomorphologic findings has not been evaluated. MATERIALS AND METHODS: We correlated cytology with mAb Das-1 test results and resection histology in 26 PCs. There were 18 intraductal papillary mucinous neoplasms (IPMN), 1 intraductal oncocytic papillary neoplasm (IOPN), 4 mucinous cystic neoplasms (MCN), 2 serous cystadenomas, and 1 cystic pancreatic neuroendocrine tumor (PanNET). HR cysts included cysts with high-grade atypia on cytology or HGD on histology, invasive carcinoma, IOPNs, and cystic PanNETs. Intestinal type IPMNs were also HR cysts on histology. RESULTS: In 17 cases (65.38%), cytology and mAb Das-1 test correlated with histology. There were 2 (7.69%) mAb Das-1 test negative HR PCs diagnosed by cytology. Five (19.23%) mAb Das-1 test positive HR PCs had mucin only or cells with low-grade dysplasia on cytology. Two mAb Das-1 test positive HR PCs had nondiagnostic cytology. HR IOPN and cystic PanNET were not detected by mAb Das-1 test. CONCLUSION: The mAb Das-1 is a sensitive and specific biomarker for detecting HR mucinous PCs. Adding cytology to mAb Das-1 testing improves the sensitivity for the detection of nonmucinous HR PC. Together, cytology with mAb Das-1 testing is more accurate than either one alone.


Subject(s)
Adenocarcinoma, Mucinous/diagnosis , Antibodies, Monoclonal/immunology , Antibodies/immunology , Cystadenoma, Serous/diagnosis , Cytodiagnosis/methods , Neuroendocrine Tumors/diagnosis , Pancreatic Cyst/diagnosis , Pancreatic Intraductal Neoplasms/diagnosis , Pancreatic Neoplasms/diagnosis , Adenocarcinoma, Mucinous/immunology , Adenocarcinoma, Mucinous/pathology , Biomarkers, Tumor/immunology , Cyst Fluid/immunology , Cystadenoma, Serous/immunology , Cystadenoma, Serous/pathology , Data Accuracy , Humans , Neuroendocrine Tumors/immunology , Neuroendocrine Tumors/pathology , Pancreatic Cyst/immunology , Pancreatic Cyst/pathology , Pancreatic Intraductal Neoplasms/immunology , Pancreatic Intraductal Neoplasms/pathology , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/pathology , Preoperative Period , Retrospective Studies , Sensitivity and Specificity
3.
Tissue Antigens ; 83(6): 409-13, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24673566

ABSTRACT

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 Adult
4.
OMICS ; 18(2): 132-41, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24351082

ABSTRACT

MALDI mass spectrometry imaging (MALDI-MSI) is currently used for clinical applications, such as biomarker identification, particularly for the study of solid tumors. The ability to map specific compounds that have been determined to be biomarkers and therapeutic targets is relevant for the evaluation of the efficacy of targeted therapies. This article describes a new method called Spectro-ImmunoHistoChemistry (SIHC), which combines the use of specific antibodies against markers and mass spectrometric imaging in the MS/MS mode. SIHC is based on direct primary antibody-antigen recognition, trypsin digestion of the antibody overlaying the markers of interest in the tissue section, and MALDI-MSI of the tryptic peptides generated from the antibody. This approach has both clinical and pharmacological applications. First, it can be used as a cross-validation method to monitor the presence specifically of a marker in a tissue section. Second, SIHC could potentially be used as a novel technology for tracking specific antibodies after in vivo injection for anti-cancer treatments. Additionally, SIHC could enable novel clinical applications of MSI, such as monitoring the efficacy of cytotoxic antibody treatments.


Subject(s)
Antibodies, Neoplasm/analysis , Carcinoma, Endometrioid/diagnosis , Cystadenoma, Serous/diagnosis , Immunohistochemistry/methods , Ovarian Neoplasms/diagnosis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Antibodies, Neoplasm/immunology , Antigen-Antibody Complex/chemistry , Antigens, Neoplasm/immunology , Carcinoma, Endometrioid/immunology , Carcinoma, Endometrioid/pathology , Cystadenoma, Serous/immunology , Cystadenoma, Serous/pathology , Female , Humans , Immunohistochemistry/instrumentation , Neoplasm Staging , Ovarian Neoplasms/immunology , Ovarian Neoplasms/pathology , Peptides/analysis , Proteolysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/instrumentation , Trypsin/chemistry
5.
Mod Pathol ; 24(12): 1612-9, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21822201

ABSTRACT

The interaction between tumor cells and inflammatory cells has an important role in cancer initiation and progression; however, this interaction has not been systematically investigated in pancreatic neoplasia. In this study, the presence of tumor-infiltrating neutrophils within and/or adjacent to neoplastic cells was investigated in pancreatic neoplasms. Areas with >10 tumor-infiltrating neutrophils/100 epithelial cells were arbitrarily classified as positive. Those with 11-15 tumor-infiltrating neutrophils were considered 'borderline' while those with >15 tumor-infiltrating neutrophils were considered 'significant'. Among 363 invasive ductal carcinomas, 15 showed significant tumor-infiltrating neutrophils (8 were micropapillary carcinomas and 7 were undifferentiated carcinomas). Of 19 mucinous cystic neoplasms with a carcinomatous high-grade papillary component, 11 showed significant tumor-infiltrating neutrophils (mean, 25; range, 14-63 tumor-infiltrating neutrophils). Among intraductal papillary mucinous neoplasms, significant tumor-infiltrating neutrophils were identified in 4/16 pancreatobiliary type, but were uncommon in other types (1/11 oncocytic and 1/23 intestinal types had borderline tumor-infiltrating neutrophils, and 0/10 gastric type had tumor-infiltrating neutrophils). Non-carcinomatous (low-grade and non-papillary) components of these neoplasms did not have tumor-infiltrating neutrophils. Tumor-infiltrating neutrophils were not striking in neuroendocrine tumors (40), serous cystadenomas (18), acinar cell carcinomas (9) or solid-pseudopapillary neoplasms (8). In conclusion, significant tumor-infiltrating neutrophils are uncommon in pancreatic ductal adenocarcinoma, and when they occur it is typically in the micropapillary and undifferentiated types with a known poor prognosis. Among pre-invasive neoplasia, tumor-infiltrating neutrophils show a predilection for papillary in-situ carcinomas of mucinous cystic neoplasms, or less commonly, pancreatobiliary-type intraductal papillary mucinous neoplasms (both of which express cell surface-associated mucin 1 (MUC1)). MUC1 expression by these tumors may have biologic implications, considering its recently established relationship with inflammatory cells in carcinogenesis, and the differential expression of mucins in pancreatic neoplasia. Larger studies are needed to investigate the association between tumor-infiltrating neutrophils and pancreatic neoplasms and their role in their clinical behavior.


Subject(s)
Carcinoma/immunology , Cystadenoma, Serous/immunology , Neutrophil Infiltration , Neutrophils/immunology , Pancreatic Neoplasms/immunology , Adenocarcinoma, Mucinous/immunology , Adenocarcinoma, Mucinous/pathology , Biomarkers, Tumor/analysis , Carcinoma/pathology , Carcinoma in Situ/immunology , Carcinoma in Situ/pathology , Carcinoma, Acinar Cell/immunology , Carcinoma, Acinar Cell/pathology , Carcinoma, Pancreatic Ductal/immunology , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Papillary/immunology , Carcinoma, Papillary/pathology , Cell Differentiation , Cystadenoma, Serous/pathology , Humans , Immunohistochemistry , Mucin-1/analysis , Neoplasm Invasiveness , Neutrophils/pathology , Pancreatic Neoplasms/pathology , Prognosis
6.
Ginekol Pol ; 80(7): 494-7, 2009 Jul.
Article in Polish | MEDLINE | ID: mdl-19697811

ABSTRACT

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/blood
7.
Cancer ; 115(13): 2891-902, 2009 Jul 01.
Article in English | MEDLINE | ID: mdl-19472394

ABSTRACT

BACKGROUND: The aim of the study was to determine whether tumor-infiltrating lymphocytes and/or tumor mitotic activity could identify subgroups of patients with advanced serous epithelial ovarian cancer who would maximally benefit from aggressive surgical cytoreduction. METHODS: Snap-frozen specimens from 134 consecutive patients with stage III or IV serous or poorly differentiated ovarian adenocarcinoma undergoing primary debulking surgery from a single US institution were characterized based on CD3(+), CD8(+), FoxP3(+) tumor-infiltrating lymphocytes, and Ki67 expression. Kaplan-Meier survival curves were estimated and compared using a log-rank statistic. A multivariate Cox model was used to estimate adjusted hazard ratios. Interactions were modeled using recursive partitioning based on maximal prognostic differentiation. RESULTS: Brisk intraepithelial CD8(+) cells (P = .035) and low Ki67 expression (P = .042) portended prolonged survival. The T-cell infiltration was more likely to occur in tumors with high proliferation index. Patients whose tumors exhibited low Ki67 expression and high intraepithelial CD8(+) frequency had a 5-year survival rate of 73.3%. Patients with aggressive tumor behavior, that is, whose tumors exhibited low frequency of intraepithelial CD8(+) T cells or high Ki67 expression were more likely to draw benefit from aggressive surgical cytoreduction. Survival was similar for patients with brisk CD8(+) T cells who had optimal or suboptimal debulking. Likewise, survival was similar for patients with low Ki67 expression who had optimal or suboptimal debulking. CONCLUSIONS: For the first time, these novel interactions of T cells, tumor proliferation index, and surgical treatment reveal that biological prognosticators may be useful for surgical decision making in ovarian cancer.


Subject(s)
Cystadenoma, Serous/surgery , Lymphocytes, Tumor-Infiltrating/immunology , Ovarian Neoplasms/surgery , Adult , Aged , Aged, 80 and over , CD3 Complex/analysis , CD8-Positive T-Lymphocytes , Cell Proliferation , Cystadenoma, Serous/immunology , Cystadenoma, Serous/pathology , Female , Forkhead Transcription Factors/analysis , Humans , Ki-67 Antigen/analysis , Middle Aged , Ovarian Neoplasms/immunology , Ovarian Neoplasms/pathology , Prognosis , T-Lymphocytes , Treatment Outcome
8.
Cytometry B Clin Cytom ; 74(4): 251-8, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18302193

ABSTRACT

BACKGROUND: Evaluation of immature myeloid and lymphoid dendritic cells (DCs) in the peritoneal fluid (PF) and peripheral blood (PB) mononuclears of women with ovarian carcinoma (n = 47) and benign ovarian tumors (n = 37). METHODS: Mononuclear cells were isolated from PF and PB, stained with monoclonal antibodies (mAbs) against DC antigens (anti-BDCA-1, anti-BDCA-2), and estimated using flow cytometry. RESULTS: The percentage of PF myeloid DC (MDC) in mononuclears was significantly lower in patients with ovarian cancer in comparison to the group of nonmalignant ovarian tumors (0.65% and 6.95%). The percentage of PF lymphoid DCs (LDCs) was higher in patients with ovarian cancer than in the reference group (0.64% and 0.09%). The percentage of PB MDCs and LDCs did not differ significantly between studied groups. In women suffering from ovarian cancer the percentage of both MDCs and LDCs was higher in the PF than in the PB. In the reference group the percentage of MDCs was higher but that of LDCs was lower in the PF than in the PB. In women with ovarian cancer, PF MDCs/LDCs ratio was lower in comparison to patients with serous cystadenoma. In PB the ratio of MDCs to LDCs did not differ significantly between studied groups. CONCLUSIONS: We concluded that MDCs population may be affected by the presence of malignant disease. LDC subsets may have influence on the local immune response in the PF of women with malignant tumors of the ovary. (c) 2008 Clinical Cytometry Society.


Subject(s)
Ascitic Fluid/cytology , Dendritic Cells/metabolism , Ovarian Neoplasms , Adult , Aged , Aged, 80 and over , Cystadenoma, Serous/immunology , Cystadenoma, Serous/pathology , Disease Progression , Female , Flow Cytometry , Humans , Leukocytes, Mononuclear/immunology , Middle Aged , Neoplasm Metastasis , Ovarian Neoplasms/immunology , Ovarian Neoplasms/pathology
9.
Adv Med Sci ; 51: 174-7, 2006.
Article in English | MEDLINE | ID: mdl-17357302

ABSTRACT

PURPOSE: The aim of the study was to estimate the myeloid and lymphoid subpopulation of dendritic cells (DCs) in the peritoneal fluid (PF) of women with ovarian tumors. MATERIAL AND METHODS: We studied 34 patients with serous cystadenocarcinoma and 29 women with serous cystadenoma. Dendritic cells were isolated from peritoneal fluid, stained with monoclonal antibodies anti-BDCA-1 and anti-BDCA-2 and estimated using flow cytometry. RESULTS: Peritoneal fluid myeloid DCs constituted 0.59% of mononuclear cells in patients with ovarian cancer and 7.2% in women with serous cystadenoma. Lymphoid DCs constituted 0.39% of PF mononuclears in women with ovarian cancer and 0.07% in patients with serous cystadenoma. The percentage of lymphoid DCs was higher in patients with ovarian cancer than in women with serous cystadenoma. The BDCA-1/BDCA-2 DCs ratio in peritoneal fluid of patients with serous cystadenoma was significantly higher in comparison to ovarian cancer. CONCLUSIONS: Decreased BDCA-1/BDCA-2 DCs ratio in patients with ovarian cancer may favour Th2 lymphocyte differentiation and/or induction of immunological tolerance.


Subject(s)
Ascitic Fluid/cytology , Dendritic Cells/cytology , Ovarian Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Ascitic Fluid/immunology , Cystadenocarcinoma, Serous/immunology , Cystadenocarcinoma, Serous/pathology , Cystadenoma, Serous/immunology , Cystadenoma, Serous/pathology , Dendritic Cells/immunology , Female , Flow Cytometry , Humans , Lectins, C-Type/analysis , Lymphocytes/cytology , Membrane Glycoproteins/analysis , Middle Aged , Myeloid Cells/cytology , Ovarian Neoplasms/immunology , Receptors, Immunologic/analysis
10.
Ann Oncol ; 16(4): 590-6, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15699022

ABSTRACT

BACKGROUND: Significant progress has been made in understanding the molecular biology of ovarian carcinoma. Along with the molecular characteristics of cancer, the patient's response to the tumour may also contribute to survival; in particular, the effect of the immune system may play an important role on survival of cancer patients. PATIENTS AND METHODS: We analysed the CD3 positive tumour-infiltrating T cells and direct molecular assessment of T cell receptors (TCRs) gamma and beta in 95 advanced ovarian carcinomas. RESULTS: Gamma/delta T cells are statistically correlated with a brief disease-free interval (P=0.036). CD3 positive tumour-infiltrating T cells are correlated with a brief disease-free interval and with survival (P=0.004 and P=0.0001, respectively). CD3 positive tumour-infiltrating T cells are associated with clinical responsiveness to chemotherapy (P=0.003). CONCLUSIONS: Further studies are required to better understand the role of gamma/delta T cells in ovarian carcinoma, yet these data underline the importance of host immune response to cancer and the need to better study immune mechanisms to modulate the therapeutic treatment of cancer.


Subject(s)
CD3 Complex/immunology , Cystadenoma, Serous/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Ovarian Neoplasms/immunology , Receptors, Antigen, T-Cell, gamma-delta/biosynthesis , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Adult , Age Factors , Aged , Cystadenoma, Serous/pathology , Cystadenoma, Serous/therapy , Disease-Free Survival , Female , Humans , Middle Aged , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Retrospective Studies
11.
Ginekol Pol ; 75(8): 609-14, 2004 Aug.
Article in Polish | MEDLINE | ID: mdl-15517784

ABSTRACT

OBJECTIVES AND DESIGN: Neutrophils play important role in first line defence an they release soluble growth and chemotactic factors and guide the recruitment of non-specific immune effector cells. We estimated the activity and ability to reduce of nitroblue tetrazolium (NBT) by peripheral blood neutrophils in women with benign or malignant ovarian tumours. MATERIALS AND METHODS: The study was performed on 43 women between the ages of 19 and 72 with ovarian tumours. Cystadenoma serosum was diagnosed in 19 women, Cystadenocarcinoma serosum in 9, and teratoma adultum in 15 women. Venous blood samples were obtained prior to the operation. The control group consisted of 30 women their age range was from 22 to 60 years. In peripheral blood samples from both groups; there leukocyte counts and total neutrophils were determined. Metabolic activity was investigated by nitroblue tetrazolium reduction spontaneous (NBTsp) test, and stimulation by latexs (NBTst) test. RESULTS: In women with ovarian tumours, the index of spontaneous NBT reduction turned out to be significantly higher than that in the control group (p<0.0001). In the group studied, the index of latex-stimulated NBT reduction was significantly lower than that in the control group (p<0.0001). CONCLUSIONS: Intensity oxidation-reduction changes of neutrophils in reduction NBT in women with ovarian tumours were observed.


Subject(s)
Neutrophil Activation , Neutrophils/metabolism , Ovarian Neoplasms/immunology , Adult , Aged , Biomarkers/blood , Case-Control Studies , Cystadenocarcinoma, Serous/immunology , Cystadenoma, Serous/immunology , Female , Humans , Lymphocyte Count , Middle Aged , Nitroblue Tetrazolium , Oxidation-Reduction , Risk Factors , Teratoma/immunology
12.
Ai Zheng ; 23(5): 573-6, 2004 May.
Article in Chinese | MEDLINE | ID: mdl-15142457

ABSTRACT

BACKGROUND & OBJECTIVE: As a multifunctional Th2-cytokine, interleukin-10 (IL-10)plays a major role in the immune response. It is well known that IL-10 is an immunosuppressive cytokine, and participates in the development and progression of various tumors. In this study, we investigated the relationship between the IL-10 level in the ascites of the patients with primary ovarian epithelial carcinoma (POEC) and immune defect in the peritoneal cavity. METHODS: The IL-10 levels in serum and ascites of 32 patients with POEC, in culture supernatants of 4 different ovarian carcinoma cell lines and in serum of 10 patients with ovarian epithelial benign tumor and 10 health women (control) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) IL-10 level in ascites was significantly higher than that in serum of patients with POEC, (159.78+/-51.20 ng/L vs 12.01+/-4.38 ng/L, P=0.000). IL-10 level in serum of the patients with POEC (12.01+/-4.38 ng/L) was significantly higher than that of the patients with benign tumor (3.79+/-2.40 ng/L, P=0.000) and control (4.45+/-2.69 ng/L, P=0.003). There was no significant difference of IL-10 level in serum between ovarian benign tumor and control (P=0.529). (2) IL-10 level in ascites of the patients with POEC was correlated with FIGO stage but not correlated with histological grade. (3) IL-10 was detectable in culture supernatants of 4 different ovarian cancer cell lines (3ao, SKOV3, CAOV3 and OVCAR). CONCLUSION: High level of IL-10 in ascites of the patients with POEC is probably associated with immune defect in their peritoneal cavity, ovarian cancer cells may promote metastasis in peritoneal cavity by secreting IL-10.


Subject(s)
Ascitic Fluid/chemistry , Interleukin-10/metabolism , Ovarian Neoplasms/immunology , Peritoneum/immunology , Adult , Aged , Cell Line, Tumor , Cystadenocarcinoma, Mucinous/immunology , Cystadenocarcinoma, Mucinous/pathology , Cystadenocarcinoma, Serous/immunology , Cystadenocarcinoma, Serous/pathology , Cystadenoma, Mucinous/immunology , Cystadenoma, Mucinous/pathology , Cystadenoma, Serous/immunology , Cystadenoma, Serous/pathology , Female , Humans , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/pathology
13.
Clin Exp Med ; 3(2): 113-8, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14598186

ABSTRACT

The antigens encoded by the major histocompability complex (HLA-DR) are cell glycoproteins that play a fundamental role in the regulation of the immune response. The prognosis of ovarian cancer is dependent on the histological type and on the clinical stage at diagnosis. Our study reports the value of HLA-DR antigen as a prognostic marker of ovarian serous adenocarcinoma. We studied 31 cases of serous ovarian cystadenoma, 12 cases of serous ovarian borderline cystadenoma, and 39 cases of well-differentiated cystadenocarcinoma for HLA-DR monoclonal antigen. We also studied the T helper marker (CD4) in the tumor stroma of the relevant cases, given that it is now known that the dependence of immune responsiveness on the class II antigens reflects the central role of these molecules in presenting antigen to T helper cells. HLA-DR was expressed in 20 of 31 cystadenomas (64.5%), 4 of 12 borderline tumors (33.3%), and in 10 of 39 invasive carcinomas (25.6%). CD4 was expressed in 9 of 31 cystadenomas (29%), 5 of 12 borderline tumors (42%), and in 26 of 39 invasive carcinomas (67%). There was a statistically significant difference for the two examined antigens in cystadenomas ( p<0.001) and invasive carcinomas ( p<0.001), whereas there was no statistical difference in borderline tumors ( p<0.5). The results showed decreased expression of HLA-DR and increased expression of CD4 as the lesion progressed to malignancy. The aberrant expression of HLA-DR by epithelial cells of cystadenomas, of borderline tumors, and of invasive adenocarcinomas agrees with the hypothesis of the adenoma/adenocarcinoma sequence. The immune attraction mechanism by low HLADR signaling seems to be of minor importance in the malignant and metastatic potential of serous ovarian tumors.


Subject(s)
Cystadenoma, Serous/immunology , HLA-DR Antigens/analysis , Ovarian Neoplasms/immunology , CD4 Antigens/analysis , Cystadenoma, Serous/pathology , Female , Humans , Ovarian Neoplasms/pathology , Prognosis
14.
Eur J Gynaecol Oncol ; 20(2): 141-3, 1999.
Article in English | MEDLINE | ID: mdl-10376434

ABSTRACT

UNLABELLED: The aim of this study was to investigate the presence of a local immunological defense mechanism of the secretory IgA class in the female genital tract. MATERIAL AND METHODS: We studied by a streptavidin-biotin method the secretory component (SC) and IgA distribution in paraffin-embedded sections of 90 formalin-fixed specimens. We studied 10 normal and 5 neoplastic cervical specimens, 20 normal, 10 hyperplastic endometrial specimens and 10 endometrial adenocarcinomas, 5 normal ovarian tubes and 30 ovarian epithelial neoplasms, serous and mucinous. A polyclonal SC and (Dako) and a mab IgA (Dako) was used and the reaction was scored from 1-3. RESULTS: Normal cervical mucosa and atrophic endometria were negative, while the basal portion of the endometrium, focally the proliferative glands, most of the secretory glands and most of the hyperplastic glands were positive for SC. IgA showed a similar distribution and a perivascular stromal reaction. Adenocarcinomas were positive for SC, but the intensity of the reaction was dependent on the differentiation of the tumors. Mucous and most serous neoplasms were negative for SC. IgA showed a similar reaction. CONCLUSION: There is evidence that the female genital tract has a local defensive immune system that may be hormone dependent. SC is a valuable marker of glandular differentiation.


Subject(s)
Genital Neoplasms, Female/immunology , Genitalia, Female/immunology , Immunoglobulin A, Secretory/metabolism , Secretory Component/metabolism , Adenocarcinoma/immunology , Case-Control Studies , Cervix Uteri/immunology , Cystadenocarcinoma, Serous/immunology , Cystadenoma, Serous/immunology , Endometrial Neoplasms/immunology , Fallopian Tubes/immunology , Female , Humans , Immunohistochemistry , Ovarian Neoplasms/immunology , Ovary/immunology , Uterine Cervical Neoplasms/immunology
15.
Int J Cancer ; 81(2): 193-8, 1999 Apr 12.
Article in English | MEDLINE | ID: mdl-10188718

ABSTRACT

Expression of blood group-related carbohydrate antigens was examined in frozen sections from a series of ovarian carcinomas of different histological types using an indirect immunoperoxidase technique. Antigenic specificities belonging to the O(H) and Lewis blood group families (H-1, H-2, Le(a), sLe(a), Le(x), sLe(x), Le(b) and Le(y)) or the mucin-core family (Tn, sTn and TF) were studied. A distinct difference in antigen expression between mucinous and other ovarian carcinomas (serous and endometrioid) was observed. Specifically, mucinous tumors tended to express sTn, Le(a) and sLe(a) strongly and homogeneously, whereas serous and endometrioid tumors rarely expressed these specificities and, in contrast, expressed Le(y) and H type 2 antigen strongly. When expressed in serous tumors, sTn was usually distributed in a heterogeneous pattern, whereas sTn expression in mucinous tumors was much more homogeneous. The distribution of Le(y) in serous tumors was noticeably homogeneous. H-1, Le(x), sLe(x), Le(b), TF and Tn specificities were rarely expressed in any type of ovarian carcinoma. Our results provide further support for the different histogenesis of mucinous and non-mucinous tumors and indicate alternative differentiation pathways for the 3 pathological subtypes of ovarian tumor. They also provide the basis for the choice of carbohydrate antigens for active and passive immunotherapy of ovarian carcinomas.


Subject(s)
Antigens, Tumor-Associated, Carbohydrate/immunology , Carcinoma, Endometrioid/therapy , Cystadenoma, Mucinous/therapy , Cystadenoma, Serous/therapy , Immunotherapy , Ovarian Neoplasms/therapy , Antibodies, Monoclonal , Antigen-Antibody Reactions , Carcinoma, Endometrioid/immunology , Carcinoma, Endometrioid/pathology , Cystadenoma, Mucinous/immunology , Cystadenoma, Mucinous/pathology , Cystadenoma, Serous/immunology , Cystadenoma, Serous/pathology , Diagnosis, Differential , Female , Humans , Ovarian Neoplasms/immunology , Ovarian Neoplasms/pathology
16.
Histopathology ; 32(2): 151-9, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9543672

ABSTRACT

AIMS: To determine the diagnostic and prognostic value of the immunohistochemical analysis of CD44 variants in benign borderline and malignant tumours of the ovary. METHODS AND RESULTS: The reactivity of tumour cells with three monoclonal antibodies, respectively, directed to all CD44 variants, CD44-v3 isoform and CD44-v6 isoform, was assessed by using an indirect immunoperoxidase technique applied to formalin-fixed, paraffin-embedded samples of 36 cases of borderline, as compared to 20 cases of benign tumours and 20 cases of carcinomas. CD44 variants were detected in 97% of borderline tumours, as compared to 60% of benign tumours and 100% of carcinomas. CD44-v3 was detected in 25% of borderline tumours, as compared to 0% of benign tumours (P = 0.003) and 55% of carcinomas (P = 0.065). The expression of CD44-v6 was detected in 28% of borderline tumours, as compared to 20% of benign tumours and 30% of carcinomas. In borderline tumours, as in carcinomas, CD44-v6, but not CD44-v3, expression was correlated with an increased proliferative index and with a higher incidence of p53 expression. CONCLUSION: Borderline tumours of the ovary present frequent quantitative and qualitative alterations in the pattern of expression of CD44 proteins. However, these alterations are unlikely to represent useful diagnostic or prognostic markers.


Subject(s)
Carcinoma/immunology , Cystadenoma, Mucinous/immunology , Cystadenoma, Serous/immunology , Hyaluronan Receptors/analysis , Ovarian Neoplasms/immunology , Adult , Antibodies, Monoclonal/metabolism , Cadherins/biosynthesis , Carcinoma/chemistry , Carcinoma/pathology , Cell Division , Cystadenoma, Mucinous/chemistry , Cystadenoma, Mucinous/pathology , Cystadenoma, Serous/chemistry , Cystadenoma, Serous/pathology , Female , Humans , Immunohistochemistry , Middle Aged , Ovarian Neoplasms/chemistry , Ovarian Neoplasms/pathology , Ovary/chemistry , Ovary/immunology , Tumor Suppressor Protein p53/biosynthesis
17.
J Neurol ; 244(2): 85-9, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9120501

ABSTRACT

In recent years several authors have described a close correlation between circulating antineuronal antibodies of different types and the occurrence of paraneoplastic neurological syndromes. Because this has not been widely accepted, we screened 300 serum samples from 181 ovarian cancer patients for the presence of circulating antineuronal antibodies by immunofluorescence. The findings were confirmed by immunoblotting. In 11 patients circulating antineuronal antibodies were detected. In 4 patients they were classified as anti-Yo and in 7 as anti-Ri, titres ranging from 1:400 to 1: 204,800. All the patients underwent thorough neurological and neurophysiological investigations, with special regard to paraneoplastic syndrome. None of them had symptoms pointing to a paraneoplastic neurological syndrome, although patients were followed up to 2 years after the first examination. Thus the frequency of circulating antineuronal antibodies in ovarian cancer patients is higher than the frequency of paraneoplastic syndromes, and antibody positivity does not necessarily lead to the appearance of a neurological paraneoplastic syndrome.


Subject(s)
Autoantibodies/blood , Autoantigens/immunology , DNA-Binding Proteins/immunology , Neoplasm Proteins/immunology , Nerve Tissue Proteins/immunology , Ovarian Neoplasms/immunology , Paraneoplastic Syndromes/immunology , Peripheral Nervous System Diseases/immunology , Ribonucleases/antagonists & inhibitors , Cystadenoma, Serous/immunology , Cystadenoma, Serous/pathology , Female , Follow-Up Studies , Humans , Neoplasm Staging , Ovarian Neoplasms/pathology
18.
Gastroenterology ; 108(4): 1230-5, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7535275

ABSTRACT

BACKGROUND/AIMS: It has been suggested that activity of pancreatic enzymes and concentrations of tumoral markers in cyst fluid may help to distinguish pseudocyst, serous, and mucinous cystadenomas. The aim of this study was to prospectively assess the reliability of preoperative biochemical and tumor marker analysis in cyst fluids obtained by fine-needle aspiration for pathological diagnosis. METHODS: Cyst fluid was obtained preoperatively by fine-needle aspiration, and biochemical and tumoral marker values were measured. The diagnosis of cystic tumors (7 serous cystadenomas and 12 mucinous tumors) was established by surgical specimen analysis. Thirty-one pancreatic pseudocysts complicating well-documented chronic pancreatitis were also studied. RESULTS: Carbohydrate antigen 19.9 levels of > 50,000 U/mL had a 75% sensitivity and a 90% specificity for distinguishing mucinous tumors from other cystic lesions. Carcinoembryonic antigen levels of < 5 ng/mL had a 100% sensitivity and an 86% specificity for distinguishing serous cystadenomas from other cystic lesions. Amylase levels of > 5000 U/mL had a 94% sensitivity and a 74% specificity for distinguishing pseudocysts from other cystic lesions. CONCLUSIONS: High carbohydrate antigen 19.9, low carcinoembryonic antigen, and high amylase levels in cyst fluid are very indicative of mucinous tumors, serous cystadenomas, and pseudocysts, respectively.


Subject(s)
Body Fluids/chemistry , Pancreatic Cyst/diagnosis , Pancreatic Neoplasms/diagnosis , Amylases/analysis , Biomarkers, Tumor/analysis , Biopsy, Needle , Body Fluids/immunology , CA-19-9 Antigen/analysis , Carcinoembryonic Antigen/analysis , Cystadenoma, Mucinous/chemistry , Cystadenoma, Mucinous/diagnosis , Cystadenoma, Mucinous/immunology , Cystadenoma, Serous/chemistry , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/immunology , Diagnosis, Differential , Feasibility Studies , Humans , Lipase/analysis , Pancreatic Cyst/immunology , Pancreatic Cyst/metabolism , Pancreatic Neoplasms/chemistry , Pancreatic Neoplasms/immunology , Pancreatic Pseudocyst/chemistry , Pancreatic Pseudocyst/diagnosis , Pancreatic Pseudocyst/immunology , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity
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