Serum IL-6 and IL-8 Correlate with Prognostic Factors in Ovarian Cancer.

The aim of the study was to correlate serum levels of IL-2, IL-5, IL-6, IL-8, IL-10, and TNF-α with clinical, laboratory, and pathological prognostic factors in patients with primary ovarian malignancy. Patients treated at the Pelvic Mass Ambulatory of the Discipline of Gynecology and Obstetrics/Oncology Research Institute (IPON) of the UFTM with confirmed diagnosis of malignant ovarian neoplasia (n = 26) were evaluated. Serum collection was performed preoperatively for the determination of tumor markers. The cytokines IL-2, IL-5, IL-6, IL-8, IL-10, and TNF-α were assayed by enzyme-linked immunosorbent assay (ELISA). The prognostic factors were compared using the Mann-Whitney test, with significance level lower than 0.05. When evaluating IL6, it was observed that higher serum levels were associated with overall survival less than 60 months (p = 0.0382). In the evaluation of IL8, higher serum levels were associated with neutrophil-to-lymphocyte ratio (NLR) ≥ 4 and platelet-to-lymphocyte ratio (PLR) ≥ 200 (p = 0.0198 and p = 0.0072, respectively), altered values of serum CA125 (p = 0.0457), and stage IIIC (p = 0.0486). Therefore, increased levels of IL-6 and IL-8 are associated with factors of worse prognosis in ovarian cancer. Additional studies with a larger sample of patients are needed to confirm the role of cytokines as prognostic factors, in the definition of treatment, and in the development of future target therapies.

[Relationship between interleukin-10 level in ascites of patients with primary ovarian epithelial carcinoma and immune defect in peritoneal cavity].

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.

Benign inflammatory pancreatic mucinous cystadenomas mimicking locally advanced cystadenocarcinomas. Presentation of 3 cases.

We report 3 cases of benign mucinous cystadenoma of the pancreas mimicking, both clinically and on imaging findings, locally advanced cystadenocarcinoma spreading to neighbouring organs (stomach, splenic and mesenteric vessels, and diaphragm). Surgical resection was performed in light of the suspicion of invasive carcinoma in all 3 cases. Histological examination of the resected specimens showed entirely benign mucinous cystadenomas associated with marked peri-tumoural inflammation that accounted for the pre-operative misdiagnoses. All 3 patients are alive 40, 47 and 54 months after surgery without evidence of tumour relapse. These cases indicate that surgery must be considered in patients with cystic tumour of the pancreas suggesting locally advanced cystadenocarcinoma, even when pre-operative imaging findings suggest tumour extension into neighbouring organs.

[Pseudo-Meigs' syndrome]. / Pseudo-Meigs' syndrom.

Cytologic examination of the body cavity effusions in patients with ovarian tumours is performed to differentiate between reactive processes and tumour spread. While detection of malignant cells is a marker of metastatic disease and a sign of bad prognosis, benign effusions affect neither disease stage nor the patient's prognosis. Determination of the presence or absence of tumour spread is based primarily on cellular morphology. As distinction between reactive mesothelial and cancer cells can be difficult, immunocytochemistry may be employed in equivocal cases. The case of a 42-year-old woman who presented with a large pelvic mass accompanied by ascites and hydrothorax is described. Cytomorphology of preoperative pleural fluid specimen was inconclusive. Immunocytochemical examination of cell block sections using: BerEP4, B72.3, CA 125, CD15, CEA, E-cadherin and calretinin was done. No epithelial cells were detected and diagnosis of reactive mesothelial cells was made. Laparotomy was performed and adnexal tumour removed. Borderline mucinous tumour of the ovary was diagnosed. There was no recurrence of the ascites or hydrothorax. The clinicopathologic features and terminology of pseudo-Meigs' syndrome are briefly reviewed. The role of ancillary studies in diagnosis of body cavity effusions is emphasized.

Selection of carbohydrate antigens in human epithelial ovarian cancers as targets for immunotherapy: serous and mucinous tumors exhibit distinctive patterns of expression.

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.

Giant syncytia and virus-like particles in ovarian carcinoma cells isolated from ascites fluid.

Ovarian cancer cells were isolated from ascites fluid of 30 different patients diagnosed with cystadenocarcinoma of ovaries. Large colonies of malignant ASC cells were observed during the first week of cell growth in vitro. Colony formation was followed by fusion of cells and formation of large multinucleated and highly vacuolated syncytia. In contrast, cells isolated from the ascites fluid produced by patients with benign mucinous cystadenoma of ovaries did not form syncytia. Nonmalignant Brenner tumor cells, isolated from the ascites fluid, also did not form syncytia. Syncytia, but not the nonmalignant tumor cells, were immunofluorescence stained with an anti-human immunodeficiency virus type 1 (HIV-1) gp120 monoclonal antibody (MAb) and MAb RAK-BrI. Both MAbs recognized cancer-associated antigens RAK (for Rakowicz markers) p120, p42, and p25. Exposure of ASC cells to either the anti-HIV-1 gp120 MAb or MAb RAK-BrI inhibited syncytium formation. PCR with HIV-1 Env-derived primers revealed DNA sequences with over 90% homology to HIV-1 gp41 in syncytia and in ovarian cancer cells but not in normal ovary cells. Electron microscopic analysis revealed viral particles, hexagonal in shape (90 nm in diameter), with a dense central core surrounded by an inner translucent capsid and dense outer shell with projections. Negative staining detected membrane-covered particles (100 to 110 nm in diameter) in the cell culture medium. Incubation of normal breast cells with viral particles resulted in drastic morphological changes and syncytium formation by the transformed breast cells. The cytopathic effects of the identified virus resembled those of spumaviruses, which, in addition to their epitopic and genetic homology to HIV-1, might suggest a common phylogeny.

Analysis of CD44 expression in serous and mucinous borderline tumours of the ovary: comparison with cystadenomas and overt carcinomas.

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.

[Cellular adhesion molecule (CD44) in ovarian tumors].

OBJECTIVE: To investigate a method of detecting adhesion molecule (CD44) contents in ovarian tumors and its clinical significance. METHODS: In 106 patients with ovarian tumors (50 benign and 56 malignant), the adhesion molecule (CD44) contents in peripheral blood lymphocytes (PBL) and in neoplastic tissues were analysed (quantitatively by using flow cytometric-immunological method). RESULT: (1) The CD44 contents in the PBL of the patients with malignant tumor were obviously higher than those of patients with benign tumors (P<0.05) and than those of the control (P < 0.01); (2) Within the group of patients with malignant tumors, the CD44 contents in the neoplastic tissues were higher than those in the PBL (0.01 < P < 0.05); There was no significant difference in CD44 contents among the different histopathological types, whether benign or malignant; (4) The CD44 contents in the PBL decreased gradually after surgery. CONCLUSION: To analyse the CD44 contents in PBL and neoplastic tissues by flow cytometry may be an important method or parameter to differentiate benign ovarian tumors from malignant tumors and to discover recurrence of metastasis of malignant tumors in early stage.

Mucinous cystadenoma of the lung.

BACKGROUND: Mucinous cystadenoma is an unusual pulmonary tumor that must be distinguished from mucinous cystic carcinoma and mucinous cystic tumors of borderline malignancy. METHODS: This study of two cases was performed to characterize mucinous cystadenoma clinically and immunohistochemically, using proliferation markers (proliferating cell nuclear antigen [PCNA], MIB1) and carcinoembryonic antigen expression. RESULTS: Pathologic examination in each instance showed unilocular cysts containing abundant clear mucus. The cysts were lined by tall mucinous epithelium, with absence of cytologic atypia and invasive growth. Proliferation markers using immunohistochemical methods showed less than 10% and 5% of labeled nuclei, respectively. Carcinoembryonic antigen immunostaining in both cases was negative. Patients remained free from recurrence for at least 2 years after surgery. CONCLUSIONS: Mucinous cystadenoma of the lung appears to be a benign neoplasm because of its clinical course and immunohistochemical low expression of proliferation markers such as PCNA and MIB1.

Preoperative cyst fluid analysis is useful for the differential diagnosis of cystic lesions of the pancreas.

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.

Extremely high levels of CA19-9 and CA125 antigen in benign mucinous ovarian cystadenoma.

A Japanese woman had a mucinous cystadenoma of the left ovary associated with very high serum levels of CA19-9 (3170 u/ml) and CA125 (1705 u/ml). Such high levels of both antigens have not been reported previously in patients with benign ovarian mucinous cystadenoma. Immunostaining demonstrated CA19-9 and CA125 in the tumor, and different patterns of expression were noted depending on the differentiation of the epithelium. The postoperative tumor marker profile suggested that no residual tumor was left after the operation.