Circulating biomarker tissue kallikrein-related peptidase KLK5 impacts ovarian cancer patients' survival.

BACKGROUND: Effective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently needed in ovarian cancer. Kallikrein-related peptidases, including KLK5, have been reported to play an important role in the course of the disease. PATIENTS AND METHODS: KLK5 antigen content was determined by enzyme-linked immunosorbent assay in ovarian cancer patients' [FIGO (International Federation of Gynecology and Obstetrics) stages I-IV, n = 52] serum as well as ascitic fluid and compared with KLK5 content in serum of patients with benign ovarian tumors (n = 45). RESULTS: KLK5 antigen content was significantly elevated in the serum of ovarian cancer patients compared with the serum of patients with benign ovarian tumors. Forty-two of 52 ovarian cancer serum samples, 42 of 43 benign ovarian tumor serum samples, and all 41 ascitic fluid samples were KLK5 positive. Elevated KLK5 antigen in serum and ascitic fluid of ovarian cancer patients was a prognostic factor for progression-free survival. CONCLUSIONS: Our data support the finding that ovarian cancer patients release significant amounts of KLK5 into serum and ascitic fluid but KLK5 antigen is low in serum of patients with benign ovarian tumors. Increased serum and ascitic fluid KLK5 levels are associated with poor patient outcome, thus underlining the importance of KLK5 as a biomarker for early detection as well as for disease management in ovarian cancer.

Significance of serum CA125 and TPS antigen levels for determination of overall survival after three chemotherapy courses in ovarian cancer patients during long-term follow-up.

PURPOSE OF INVESTIGATION: To evaluate the prognostic significance for overall survival rate for the marker combination TPS and CA125 in ovarian cancer patients after three chemotherapy courses during long-term clinical follow-up. METHODS: The overall survival of 212 (out of 213) ovarian cancer patients (FIGO Stages I-IV) was analyzed in a prospective multicenter study during a 10-year clinical follow-up by univariate and multivariate analysis. RESULTS: In patients with ovarian cancer FIGO Stage I (34 patients) or FIGO Stage II (30 patients) disease, the univariate and multivariate analysis of the 10-year overall survival data showed that CA125 and TPS serum levels were not independent prognostic factors. In the FIGO Stage III group (112 patients), the 10-year overall survival was 15.2%; while in the FIGO Stage IV group (36 patients) a 10-year overall survival of 5.6% was seen. Here, the tumor markers CA125 and TPS levels were significant prognostic factors in both univariate and multivariate analysis (p < 0.0001). In a combined FIGO Stage III + FIGO Stage IV group (60 patients with optimal debulking surgery), multivariate analysis demonstrated that CA125 and TPS levels were independent prognostic factors. For patients in this combined FIGO Stage III + IV group having both markers below respective discrimination level, 35.3% survived for more than ten years, as opposed to patients having one marker above the discrimination level where the 10-year survival was reduced to 10% of the patients. For patients showing both markers above the respective discrimination level, none of the patients survived for the 10-year follow-up time. CONCLUSION: In FIGO III and IV ovarian cancer patients, only patients with CA 125 and TPS markers below the discrimination level after three chemotherapy courses indicated a favorable prognosis. Patients with an elevated level of CA 125 or TPS or both markers after three chemotherapy courses showed unfavorable prognosis.

Vascular endothelial growth factor (VEGF) concentration in sera and tumor effusions from patients with ovarian carcinoma.

VEGF is an important angiogenic cytokine with a critical role in tumor angiogenesis. VEGF concentrations were measured using an ELISA assay, detecting VEGF165 isoform, in tumor cyst and/or ascitic fluids and in sera of 86 patients with malignant neoplasms and in 53 patients with benign ovarian neoplasms. VEGF levels were significantly elevated in the sera and cyst fluids of carcinoma patients compared with patients who had benign neoplasms. In carcinoma patients, statistically higher VEGF levels were detected in tumor effusions than in corresponding sera. The differences between VEGF values in sera and tumor effusions in relation to histological subtypes of ovarian carcinoma and FIGO stages were statistically insignificant. High VEGF levels in ascitic fluids appeared to be significantly associated with shorter disease-free survival and overall survival In multivariate analysis, besides FIGO stage and age of patients, only serum VEGF concentration was an independent prognostic factor for overall survival. The elevated VEGF levels in sera and tumor effusions of patients with FIGO stages I/II indicated that angiogenesis promoted by VEGF is a continuous process, independent of clinical advancement of the disease.

Relations between the expression of p53, c-erbB-2, Ki-67 and HPV infection in cervical carcinomas and cervical dysplasias.

BACKGROUND: The analysis of mutual relations between HPV infection and the expression of cancer gene products and proliferative activity in cervical carcinomas and dysplasias. MATERIALS AND METHODS: The expression of p53, c-erbB-2 oncoproteins and proliferative activity (Ki-67) was evaluated immunohistochemically in 41 cervical carcinomas and 29 dysplasias. HPV infection (type 16, 18) was assessed by in situ hybridization technique. RESULTS: HPV-positive carcinomas were found in 68.3% of cases. HPV type 16 infection were detected in 54% and HPV 18 in 39% of carcinomas. Simultaneous appearance of both virus types was shown in 25% of carcinomas. In dysplastic lesions, HPV infection was observed in 62.1% of cases. HPV type 16 was found in 34.5% and HPV 18 in 44.8% of patients. Both virus types were found in 17.2% of dysplasias. HPV infection was more extensive in cervical carcinomas than in dysplasias. Similarly the expression of oncoproteins was more intensive and referred to a higher percentage of cells in carcinomas. No relations between p53, c-erbB-2 overexpression and HPV infection were found. Ki-67 activity was found in a higher percentage of HPV-positive than in HPV-negative, both carcinomas and dysplasias. CONCLUSIONS: HPV infection, especially accompanied by increase of proliferative activity in dysplasias may define the cell subpopulation predisposed to malignant process development. The employment of in situ hybridization technique appears to be useful in detecting the viral infection in cytological smears even with no morphological changes in the cells.

Expression and mutation of p53 in tumor effusion cells of patients with ovarian carcinoma: response to cisplatin-based chemotherapy.

p53 alterations are considered as one of the most important factors responsible for drug resistance in ovarian carcinomas, although the relationship between p53 gene status and response to cisplatin-based chemotherapy in ovarian cancer patients remains unclear. The aim of the study was to evaluate the relationship between p53 protein accumulation, p53 gene mutation and response to cisplatin-based chemotherapy in patients with ovarian carcinoma considering conventional clinicopathological parameters. Tissue sections and corresponding cyst and/or ascitic fluid cells from 79 patients with epithelial ovarian cancer were analyzed immunohistochemically for p53 expression. The PCR-SSCP analysis was performed in 25 cases and the results were compared with immunohistochemical data. It was demonstrated that p53 expression reaching approximately 50% of positive cells in immunostaining was usually associated with PCR-amplified exons showing abnormal migration and suspected for mutation. p53 gene changes were not correlated with histological structure, grade of differentiation or residual tumor after cytoreductive surgery, despite being detected more frequently in III/IV than in II FIGO stages and in patients with residual disease above 2 cm. A significant correlation between p53 accumulation and p53 gene alteration and poor response to cisplatin-based chemotherapy was shown. The overall survival time of patients decreased with an increase in p53 protein expression. A strong p53 expression especially accompanied by p53 changes detectable by PCR-SSCP analysis appears to be a good indicator of the resistance to cisplatin-based chemotherapy. The association between strong p53 overexpression and shorter overall survival time was also revealed.

Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients.

OBJECTIVE: To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients. METHODS: We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients. The prognostic significance of CA 125 and TPS levels above the discrimination value (25 kU/L and 100 U/L, respectively) was examined by univariate and multivariate analyses. RESULTS: Of the 213 cases included, 64 patients were staged as FIGO I + II and 149 patients were staged as FIGO III + IV. Tumor marker levels in stage I + II were not correlated with survival. However, stage III and IV patients with elevated levels of CA 125 or TPS after three chemotherapy courses had a worse 2-year OS (69% vs 26%, P < 0.0001 and 57% vs 20%, P < 0.0001, respectively) than patients with normal levels of the markers. In univariate analysis the result of operation (staging laparatomy and partial debulking) and advanced FIGO stage (IV) were also adverse prognostic factors. Independent factors predictive of low 2-year OS by multivariate analysis were staging laparotomy, TPS elevated, and CA 125 elevated. The only factors predictive of low 1-year OS were TPS elevated and staging laparotomy. CONCLUSIONS: Ovarian cancer patients with elevated CA 125 levels after three chemotherapy courses have a poor prognosis. However, the prognostic accuracy can be significantly increased by the parallel determination of serum TPS.

Morphological and phenotypic characterization of a new established ovarian carcinoma cell line (OvBH-1).

BACKGROUND: A limited number of permanent ovarian carcinoma cell lines have been described so far and the majority of them have been derived from ovarian ascitic fluid cells taken from patients with serous ovarian carcinoma usually after chemotherapy treatment. MATERIALS AND METHODS: The cells for culture were obtained from ascitic fluid cells of a patient with ovarian clear cell carcinoma. Cytomorphological analysis of cultured cells at early and late passages was performed by hematoxylin-eosin staining. Immunophenotypic characterization of cells was performed using the following monoclonal antibodies against: intermediated cellular filaments (CK 6/18, CK 7, CK 1,5,6,8,10,14,18, V9) ovarian carcinoma-associated antigens (OC125, OV-TL3), carcinoembryonic antigen, p53 and c-erbB-2 oncoproteins. RESULTS: In the established ovarian carcinoma cell line (OvBH-1) two morphologically distinct cell types were recognized. Cytomorphologically the dominating type appears to frankly malignant features. The second cell subtype showed a lower degree of malignant features. The epithelial origin of both cell types was confirmed by immunohistochemical staining using antibodies against different cytokeratin epitopes. The expression of tumor-associated antigens (CA125, OV-TL3) was found in both cell subtypes reflecting their origin from ovarian carcinoma. The cell line was negative for CEA staining. The genetic defects of cultured cells were revealed by detection of p53 and c-erbB-2 overexpression. The level of both oncoproteins and especially c-erbB-2 was higher in the cell subtype with frankly malignant morphological features. CONCLUSIONS: A new established, well characterized ovarian clear cell carcinoma line OvBH-1 provides an experimental model for further investigation of the biological alterations responsible for carcinogenesis and chemoresistance of this uncommon subtype of epithelial ovarian carcinomas.

Analysis of the immunoreactivity of three anti-p53 antibodies and estimation of the relations between p53 status and MDM2 protein expression in ovarian carcinomas.

BACKGROUND: The p53 growth suppressor is inactivated in human tumors by several distinct mechanisms, such as point mutations, binding to viral proteins and association with the MDM2 protein. Little is known about the expression of different immunologically distinct forms of p53 and MDM2 protein in human tumors and especially in ovarian carcinomas. MATERIALS AND METHODS: The overexpression of p53 and MDM2 oncoproteins was examined in a series of 46 ovarian carcinomas, taking into account the conventional pathological variables. The comparison of p53 and MDM2 expression in tissue sections and respective cyst and-or ascitic fluid cells was also performed. For the determination of the p53 expression the reactivity of three commonly used anti-p53 antibodies (DO7, PAb240, PAb1620), which detect immunologically distinct subclasses of p53, were analyzed in relation to the MDM2 status in individual patients. RESULTS: The detection of the p53 expression was clearly related to the antibody applied. DO7 antibody appears to be superior to both PAb240 and PAb1620 in immunohistochemical tests. Nuclear MDM2 protein overexpression was found in 17.4% of cases and usually it was associated with p53 accumulation. There was no significant correlation between p53 as well as MDM2 expression and histological subtypes, staging and grading parameters of carcinomas however p53 accumulation was detected more often in III/IV than in I/II FIGO stages. CONCLUSION: In ovarian carcinomas significant inter- and intratumoral heterogeneity in p53 and MDM2 expression was identified and different MDM2/p53 phenotypes were revealed. The restriction of MDM2 overexpression to a small subset of neoplasms indicates that this oncoprotein plays a minor role in ovarian carcinogenesis.

Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas.

The overexpression of three growth factor receptors: epidermal growth factor receptor (EGFR), ERB B2 and ERB B3 was evaluated immunohistochemically in 77 malignant and 15 benign colorectal neoplasms considering clinicopathological variables (histological structure, grade of differentiation, tumor localization, clinical stage of the disease). The relationship between the coexpression of EGFR-related proteins in individual patients was also evaluated. EGFR expression was revealed in comparable percentages of colorectal adenoma and in adenocarcinoma cases (80% and 70%) while ERB B2 expression was detectable more frequently in adenoma than in adenocarcinoma cases (87% and 54%). The presence of ERB B3 was observed in a higher percentage of adenocarcinoma than adenoma cases (65% and 40%). There was no correlation between the expression of studied tyrosine kinase receptors and histological grade or Dukes' clinical stage and localization (proximal or distal) of colorectal adenocarcinoma. The incidence of EGFR and ERB B2 expression was higher in tubulovillous (100% for both receptors) than in tubular adenomas (63% and 75%), while the ERB B3 receptor was revealed more frequently in tubular than in tubulovillous neoplasms (50% and 28%). These differences appeared to be statistically nonsignificant. The concomitant expression of two growth factor receptors was observed in a higher percentage of colorectal adenomas than adenocarcinomas, and the coexistence of three growth factors was revealed in comparable percentages in malignant and benign colorectal tumors. Our results support the promotional rather than direct transformational role for the EGFR supergene family in colorectal tumorigenesis. The frequently observed coexpression of more than one EGFR-related protein in colorectal neoplasms indicates the possible cooperation of these receptors in mitogenic signaling transduction, facilitating the development and maintenance of the malignant phenotype.

Serum levels of CA 125 and TPS during treatment of ovarian cancer.

Two hundred and sixty ovarian cancer patients (including all FIGO stages) were enrolled in a prospective multicentre study. In this interim study we analyzed 206 patients receiving combined chemotherapy for at least 3 courses for two-year overall survival (OS). CA 125 and TPS were applied for monitoring treatment and the relationship between marker levels, marker changes and clinical assessments was established. Preoperative CA 125 or TPS levels were not correlated with OS in FIGO stage I and II patients. After 3 chemotherapy courses the marker levels were not correlated with OS in stage I and II. Partial debulking in stage II patients was a bad prognostic factor. CA 125 or TPS levels (using a CA 125 discrimination level of 25 kU/l and a TPS discrimination level of 100 U/l) after 3 courses of chemotherapy were highly significantly correlated with OS in FIGO stages III and IV patients: CA 125 two-year OS 67% versus 26% (p < 0.0001) and TPS two-year OS 55% versus 22% (p < 0.0001). The prognostic value of CA 125 levels after 3 chemotherapy courses could be further increased by combining CA 125 and TPS levels. When both CA 125 and TPS levels were below their respective discrimination levels, the two-year overall survival was 75%. When both levels were above the discrimination level, the two-year overall survival was only 17%.

Prognostic significance of CA 125 and TPS levels after chemotherapy in ovarian cancer patients.

The analysis of survival data of patients with epithelial ovarian cancer proved that both CA 125 and TPS were good markers for clinical outcome prediction. Patients receiving chemotherapy were analyzed for 2-year overall survival (OS). Kaplan-Meier survival analysis showed highly significant differences in OS between patients with stage I+II (survival for 2 years 68%) and stage III+IV (survival for 2 years 33%; p = 0.0008). CA 125 levels above or below 35 kU/I and TPS levels above or below 80 U/l after 3 chemotherapy courses were not significantly correlated with OS in stage I+II patients (p = 0.06 respectively 0.07). However, in the subgroup of patients with stage III+IV the cut-off levels of CA 125 and TPS were excellent discriminators of OS: With CA 125 levels below the cut-off 52% of the patients survived, while with CA 125 levels above the cut-off only 13% survived (p < 0.0001). With TPS levels below the cut-off 49% of the patients survived, while with levels above the cut-off only 19% of the patients survived (p < 0.0001). In the subset of patients with CA 125 levels less than 35 kU/I after 3 chemotherapy courses (n = 50) analysis of their TPS levels allowed further discrimination of the prognostic significance. With TPS levels below the cut-off 63% of the patients survived, while 35% of the patients survived with TPS levels above the cut-off. The sum value of CA 125 and TPS cut-off values (115) as discriminator correlated even better with survival rate: With levels below this sum value 63% of the patients survived, while this was only 17% with sum values above the summed cut-off level (p = 0.0004). The extent to which the tumor was removed at operation also correlated with the 2 years survival rate. None of the patients with a staging laparotomy (n = 10) showed a 2-years survival. The difference in OS between patients with complete debulking and partial debulking was significant: OS 51% versus 23% (p = 0.027). Prognosis was not significantly correlated with histological type.

Expression of epidermal growth factor receptor family proteins (EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis.

The expression and coexpression of EGFR, c-erbB-2 and c-erbB-3 in 21 gastric cancers and 20 chronic gastritis was examined using immunohistochemistry on fresh frozen tissues considering clinicopathological variables. Generally, gastric cancer patients showed a higher incidence of EGFR, c-erbB-2 and d-erbB-3 overexpression than the group with chronic gastritis (81% and 43%; 38% and 45%; 35% and 20%, respectively), however, statistically significant differences were found only for EGFR expression (p = 0.01). No association between immunoreactivity of all growth factor receptors and the histopathological structure of gastric cancer was observed. EGFR and c-erbB-3 proteins were detected more frequently in patients with III/IV than in I/II of TNM stages, while c-erbB-2 overexpression was higher in I/II vs. III/IV stages. In chronic gastritis with intestinal metaplasia and or coexisting carcinoma lesions, a higher frequency of the expression of studied proteins was observed in comparison with chronic gastritis without those alternations; however, these differences were statistically insignificant. The percentage of positive cases with coexpression of two proteins was comparable in gastric cancer and chronic gastritis (33% and 35%) but the simultaneous expression of all three receptors was evident only in gastric cancer (19%). Our results indicate that at least one or two members of EGFR related receptors could appear in the early stages of gastric tumorigenesis. The enhancement of c-erbB-2 and c-erbB-3 reactivity seems to cooperate with EGFR activation in the gastric cancer development. Our results indicate the promotional rather than direct transformational role for EGFR supergene family in gastric carcinogenesis.

Epidermal growth factor receptor and c-erbB-2 oncoproteins in tissue and tumor effusion cells of histopathologically different ovarian neoplasms.

The overexpression of two growth factor receptors - epidermal growth factor receptor (EGFR) and c-erbB-2 - was evaluated immunohistochemically in malignant and benign ovarian neoplasms, considering the stage of the disease and histology of tumors. The comparison of EGFR and c-erbB-2 reactivity in tissue sections and respective cyst and/or ascitic fluid cells was also performed. c-erbB-2 expression was detected in 44.4% of ovarian carcinomas, and in benign neoplasms there was no evidence of its staining, while EGFR reactivity was found both in malignant (58.7%) and benign (50%) tumors. Significant heterogeneity of staining was observed, however, the relationship between EGFR and c-erbB-2 expression in tissue sections and cyst and/or ascitic fluid cells in individual patients was evident. The expression of both growth factor receptors was not correlated with histopathological subtypes of ovarian neoplasms. The c-erbB-2 oncoprotein was detected more frequently in III/IV than in I/II stages according to the criteria of the International Federation of Gynecology and Obstetrics (FIGO) and the EGFR expression was independent of the clinical advancement of the disease. The coexpression of c-erbB-2 and EGFR was shown in 32% of ovarian carcinomas, and it dominated in cases with FIGO stages III/IV. Our results indicate that the increase of the EGFR expression appears to be associated with early stages of ovarian tumorigenesis, and the enhancement of c-erbB-2 reactivity may cooperate with EGFR activation in the development and progression of ovarian carcinomas.

p53 autoantibodies in the sera, cyst and ascitic fluids of patients with ovarian cancer.

The presence of p53 autoantibodies and p53 protein overexpression in ovarian carcinoma patients were determined and compared. p53 antibodies were detected in sera samples, cyst and/or ascitic fluids of individual patients by two separate techniques (ELISA assay and immunoblot). p53 protein accumulation was assessed immunohistochemically in tissue sections and corresponding tumor effusion cells. The relations between p53 overexpression, the presence of p53 autoantibodies and histology of tumors, grade of differentiation and clinical stage of the disease were considered. p53 expression was found in 20 of 46 (43.5%) ovarian carcinomas and significant relationship between p53 reactivity in tumor tissue and effusion cells in individual patients was evident. In the subset of carcinomas with detectable p53 accumulation only two cases (one serous, one endometrioid) were associated with the presence of p53 autoantibodies (10%). Among 26 p53- negative carcinomas also two cases (7.6%) were seropositive. The strong correlation between the presence of p53 autoantibodies in the sera and respective cyst or ascitic fluids were revealed with no exception of this coincidence. There was no association between the detection of antibodies against p53 and FIGO stage and tumor grade. Our results clearly indicate that p53 overexpression is not sufficient to elicit p53 humoral response in ovarian carcinoma patients. The presence of p53 autoantibodies in this type of cancer is not a frequent event and their importance as independent prognostic factor seems to be very limited.

Prospective studies of p53 and c-erbB-2 expression in relation to clinicopathological parameters of human ductal breast cancer in the second stage of clinical advancement.

BACKGROUND: The association between p53 and c-erbB-2 overexpression relation to ER status in ductal breast carcinoma is still unclear. Our aim was investigate the prognostic importance of the overexpression of c-erbB-2, p-53 factor, and ER status in stage II of human ductal breast cancer. MATERIALS AND METHODS: Th. expression of c-erbB-2 and p53 oncoproteins was evaluated by immunoperoxidase technique (PAP) in 62 cases of ductal breast carcinoma. The relationship between these cell growth regulatory factors was estimated and compared with the presence estrogen receptor (ER), tumor grading, tumor size, lymph node involvement, age patients and number of relapses up to the second year after surgery. RESULTS: c-erbB-2 overexpression was found in 44% and p53 in 45% of carcinomas. ER level was usually inversely proportional to the presence of studied molecular markers. Stratifying patients on the basis of c-erbB-2, p53 and ER status revealed that the combination c-erbB-2 and p53 overexpression accompanied by undetectable ER, identified the population of poorly differentiated tumors and patients with a high incidence of axillary lymph node metastases and shorter relapse time. On the other hand, undetectable values of molecular markers were associated with a low grade of tumors and a lack of lymph nodes involvement. CONCLUSIONS: Estimation of c-erbB-2, p53 and ER status seems to be a powerful tool to discriminate between different phenotypes of breast carcinoma. c-erbB-2 and p53 oncoproteins have been recognized as independent molecular markers of aggressive tumor behaviour.

p53, c-erbB-2 and p21ras expression in tumor effusion cells of patients with histopathologically different ovarian neoplasms.

The overexpression of p53, c-erbB-2 and p21ras gene products was evaluated immunohistochemically in ovarian carcinomas, borderline, and benign neoplasms. All studies were performed on cytospin preparations of cyst and/or ascitic fluid cells and mutual relations between oncoproteins were analysed. p53 and c-erbB-2 immunostaining was observed in 50% and 48.5% of ovarian carcinomas and in 30% and 35% of ovarian borderline tumors respectively, however in the last group the intensity and percentage of stained cells were considerably lower. In ovarian benign neoplasms there was no evidence of p53 and/or c-erbB-2 expression. The trend for serous carcinoma to have a higher p53 and c-erbB-2 expression than endometrioid and mucinous carcinomas was observed. p53 and c-erbB-2 oncoproteins were detected more frequently in the III/IV than in the I/II stages of the disease. The expression of p21ras was detected in 91% of malignant, 65% of borderline and 50% of benign neoplasms. p21ras reactivity was independent of the histopathological structure of ovarian carcinomas and it was comparable in I/II and III/IV FIGO stages. Our results indicate that p21ras overexpression appears to be an early genetic alteration in ovarian tumorigenesis, followed by the appearance of p53 and c-erbB-2 oncoproteins. It is likely that enhanced p53 and c-erbB-2 expression may cooperate with ras gene activation to produce a particularly aggressive phenotype. Our study supports the concept that development of ovarian carcinoma is the end result of a complex multistep process involving the complementary action of different cancer causing genes.

TPS and CA 125 levels in serum, cyst fluid and ascites of patients with epithelial ovarian neoplasms.

The serum markers TPS and CA 125 were determined in serum, cyst fluid and ascites in ovarian carcinoma patients and in patients with benign ovarian neoplasms. The levels of TPS and CA 125 were significantly higher in malignant and benign tumor cysts and ascitic fluids than in corresponding patients sera (p < 0.005 for TPS, p < 0.0001 for CA 125). The concentrations of cyst fluid TPS and CA 125 were also usually higher in cancer patients than in patients with benign ovarian neoplasms. TPS and CA 125 were elevated in a higher proportion of ovarian cancer patients sera than in benign ovarian patients' sera (p < 0.001 for both markers). Serum preoperative TPS and CA 125 levels were significantly higher in patients with advanced disease (FIGO stage III/IV) than in patients with early stage disease (FIGO stage I/II, p = 0.002, p < 0.05 respectively). When histology was considered, small differences in the marker signals were noted for TPS and CA 125 with the exception of mucinous neoplasms, where TPS showed a markedly higher signal. These results suggest that the combined use of TPS and CA 125 could be of additive value for the identification of epithelial ovarian neoplasms. Postsurgical TPS sera levels achieved the normal values faster than CA 125 suggesting that determination of TPS concentration before and 3 days after surgery seems to be valuable for the evaluation of radical surgery.

nm23 expression in tissue sections and tumor effusion cells of ovarian neoplasms.

The genetic changes involved in the metastatic process of ovarian epithelial cancer remain undetermined. The expression of nm23, a putative metastasis-suppressor gene product, was assessed immunohistochemically in malignant and benign ovarian neoplasms, considering histology of tumors and clinical advancement of disease. Comparison of nm23 protein content in tissue sections and respective cyst and/or ascitic fluid cells was also performed. Significant heterogeneity of nm23 immunostaining was observed, and no correlation with histological subtype of ovarian carcinoma was found. Expression of nm23 was higher in carcinomas compared with benign tumors. A significant trend to have a higher nm23 reactivity in ascitic fluid cells vs. primary tumors was observed. Our results indicate that the increase of nm23 reactivity is activated in the early stages of the disease and that the progression of ovarian carcinoma is accompanied by overexpression of nm23 protein. Our observations did not confirm the postulated role of nm23 as a suppressor gene in ovarian cancer.

[Studies of human papillomavirus infection (HPV) and expression of oncoprotein p 21 in cervix neoplasms]. / Badania nad zakazeniem wirusem ludzkiego brodawczaka (HPV) i ekspresja onkoproteiny p 21 w rakach szyjki macicy.

Frequencies of HPV type 16 and 18, evaluated by in situ hybridization technique in uterine cervix carcinomas of the IIIrd stage of clinical advancement, were 54% and 36.5% respectively. Presence of p 21 protein was detected in 85.3% cases of the cancers and showed no relation to HPV infection.

Relationship between c-erbB-2 oncoprotein, epidermal growth factor receptor, and estrogen receptor expression in patients with ductal breast carcinoma. Association with tumor phenotypes.

The expression of c-erbB-2 oncoprotein, epidermal growth factor receptor (EGFR) and estrogen receptor (ER) was evaluated by the immunoperoxidase technique (PAP) in ductal breast carcinomas. The relationship between these cell growth regulatory factors was considered and compared with tumor grading, tumor size, lymph node involvement and age of patients. Stratifying of patients on the basis of c-erbB-2, EGFR and ER status indicated that the combination of c-erbB-2 overexpression accompanied by high EGFR value and undetectable ER, identified poorly differentiated tumors and patients with high incidence of axillary lymph node metastases, while high EGFR expression and negative c-erbB-2 staining was connected only with poor tumor grade. The undetectability of molecular markers was associated with higher histological grade and lack of lymph node involvement. Our results indicate that the comparison of c-erbB-2, EGFR and ER status seems to be a powerful tool in discriminating breast carcinomas with different biological phenotypes.