Biomedical subjects

Manfred Dietel

Publications and source records attributed to Manfred Dietel.

72 records · Page 4Linked to original sources

PubMed2002

Expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) in primary human ovarian carcinoma.

The mitogen-activated protein kinase phosphatase-1, MKP-1 (CL100) is involved in inactivation of MAP-kinase pathways, regulation of stress-responses and suppression of apoptosis. We investigated expression of MKP-1 in 90 cases of primary ovarian tumors, 11 normal ovaries as well as 4 ovarian carcinoma cell lines. Immunohistochemical expression of MKP-1 protein was reduced in tissue from LMP tumors and invasive ovarian carcinomas compared to normal ovaries and cystadenomas. A moderate to strong expression of MKP-1 was detected in 57.6% of invasive ovarian carcinomas. In a descriptive univariate survival analysis, MKP-1 expression was a prognostic marker for shorter progression-free survival of patients with invasive ovarian carcinomas. Patients with carcinomas positive for MKP-1 had a median progression-free survival of only 18.3 months compared to 40.6 months for patients with carcinomas negative for MKP-1 (log-rank test, p = 0.019). Other prognostic parameters for progression-free survival were FIGO stage, grade and pT stage. In an exploratory multivariate analysis, we found that MKP-1 expression as well as FIGO stage and grade were independent prognostic factors for progression-free survival. In contrast to progression-free survival, we did not find any influence of MKP-1 expression on patient overall survival. We investigated expression and regulation of MKP-1 mRNA by Northern Blot in vitro using 4 ovarian carcinoma cell lines (SKOV-3, OVCAR-3, CAOV-3, OAW-42). MKP-1 mRNA was inducible by interleukin-1beta and tumor necrosis factor-alpha in SKOV-3 and OVCAR-3 cells, whereas CAOV-3 and OAW-42 expressed MKP-1 mRNA constitutively. In OVCAR-3 cells MKP-1 mRNA levels were strongly inducible upon treatment of cells with cisplatin. Our data indicate that MKP-1 is expressed in a subset of ovarian carcinomas and regulated by inflammatory mediators. Expression of MKP-1 may be associated with shorter progression-free survival times. Further studies are needed to determine whether MKP-1 expression is a clinically useful marker to estimate patient prognosis as well as the response to chemotherapy.

Carcinoma↗

PubMed2002

Nucleolin as activator of human papillomavirus type 18 oncogene transcription in cervical cancer.

High risk human papillomaviruses (HPVs) are central to the development of cervical cancer and the deregulated expression of high risk HPV oncogenes is a critical event in this process. Here, we find that the cell protein nucleolin binds in a sequence-specific manner to the HPV18 enhancer. The DNA binding activity of nucleolin is primarily S phase specific, much like the transcription of the E6 and E7 oncoproteins of HPV18 in cervical cancer cells. Antisense inactivation of nucleolin blocks E6 and E7 oncogene transcription and selectively decreases HPV18(+) cervical cancer cell growth. Furthermore, nucleolin controls the chromatin structure of the HPV18 enhancer. In contrast, HPV16 oncogene transcription and proliferation rates of HPV16(+) SiHa cervical cancer cells are independent of nucleolin activity. Moreover, nucleolin expression is altered in HPV18(+) precancerous and cancerous tissue from the cervix uteri. Whereas nucleolin was homogeneously distributed in the nuclei of normal epithelial cells, it showed a speckled nuclear phenotype in HPV18(+) carcinomas. Thus, the host cell protein nucleolin is directly linked to HPV18-induced cervical carcinogenesis.

Base Sequence↗

PubMed2002

Multiple mechanisms confer different drug-resistant phenotypes in pancreatic carcinoma cells.

PURPOSE: Drug-resistant phenotypes of cancer cells may be caused by complex multimodal mechanisms of resistance. In order to gain further insighte into these mechanisms, a P-glycoprotein-mediated multidrug-resistant phenotype induced by daunorubicin-selection and an alternative drug resistance due to treatment with mitoxantrone were investigated in pancreatic carcinoma-derived cells. METHODS: For assessing cross-resistance against various drugs, cell proliferation assays were performed. Drug accumulation was measured by flow cytometry. Messenger RNA expression was analyzed by Northern blot and RT-PCR, whereas protein expression was determined by Western blot. Catalytic activity of DNA-topoisomerases (Topo) II was determined by the decatenation assay. RESULTS: In mitoxantrone-selected EPP85-181RNOV cells a decreased accumulation of mitoxantrone and daunorubicin was observed in the absence of P-glycoprotein, multidrug resistance protein or breast cancer resistance protein over-expression. An approximately twofold decrease of DNA topoisomerase II catalytic activity could be observed in both drug-resistance-exhibiting cell lines. The reduction of Topo II catalytic activity was reflected by decreased expression of Topo IIalpha and IIbeta mRNAs and proteins. CONCLUSIONS: The decreased drug accumulation in EPP85-181RNOV cells indicates that alternative transport events are occurring. The decreased catalytic activity and expression of Topo II indicate that modulation of Topo II catalytic activity contributes to both drug-resistant phenotypes in pancreatic carcinoma cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Impact of BCRP/MXR, MRP1 and MDR1/P-Glycoprotein on thermoresistant variants of atypical and classical multidrug resistant cancer cells.

The impact of the ABC transporters breast cancer resistance protein/mitoxantrone resistance associated transporter (BCRP/MXR), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance gene-1/P-glycoprotein (MDR1/PGP) on the multidrug resistance (MDR) phenotype in chemoresistance and thermoresistance was investigated in the parental human gastric carcinoma cell line EPG85-257P, the atypical MDR subline EPG85-257RNOV, the classical MDR subline EPG85-257RDB and their thermoresistant counterparts EPG85-257P-TR, EPG85-257RNOV-TR and EPG85-257RDB-TR. Within the atypical MDR subline EPG85-257RNOV expression of BCRP/MXR and of MRP1 were clearly enhanced (vs. parental and classical MDR lines). MDR1/PGP expression was distinctly elevated in the classical MDR subline EPG85-257RDB (vs. parental and atypical MDR sublines). In all thermoresistant counterparts basal expression of BCRP/MXR, MRP1 and MDR1/PGP was increased relative to thermosensitive sublines. Although it could be shown that the overexpressed ABC transporters were functionally active, however, no decreased drug accumulations of doxorubicin, mitoxantrone and rhodamine 123 were observed. Thus, expression of BCRP/MXR, MRP1 and MDR1/PGP was found to be dependent on the appropriate type of chemoresistance; correlating with a classical or atypical MDR phenotype. Within the thermoresistant variants, however, the increase in ABC transporter expression did obviously not influence the MDR phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

YB-1 relocates to the nucleus in adenovirus-infected cells and facilitates viral replication by inducing E2 gene expression through the E2 late promoter.

The adenovirus early proteins E1A and E1B-55kDa are key regulators of viral DNA replication, and it was thought that targeting of p53 by E1B-55kDa is essential for this process. Here we have identified a previously unrecognized function of E1B for adenovirus replication. We found that E1B-55kDa is involved in targeting the transcription factor YB-1 to the nuclei of adenovirus type 5-infected cells where it is associated with viral inclusion bodies believed to be sites of viral transcription and replication. We show that YB-1 facilitates E2 gene expression through the E2 late promoter thus controlling E2 gene activity at later stages of infection. The role of YB-1 for adenovirus replication was demonstrated with an E1-minus adenovirus vector containing a YB-1 transgene. In infected cells, AdYB-1 efficiently replicated and produced infectious progeny particles. Thus, adenovirus E1B-55kDa protein and the host cell factor YB-1 act jointly to facilitate adenovirus replication in the late phase of infection.

Active Transport, Cell Nucleus↗

PubMed2002

Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases.

Comparative genomic hybridization (CGH) was used to screen 54 advanced colon carcinomas. i.e., 24 primary tumors and 30 metastases, for chromosomal alterations. Using a sensitive statistical method for the determination of DNA imbalances and histograms for analysis of the incidence of changes, we identified the DNA over-representation of chromosome 20q as the most common alteration being present in 100% of cases. High incidence deletions were observed on 18q21-18q23 (96%), 4q27-4q28 (96%), 4p14 (87%), 5q21 (81%), 1p21-1p22 (72%), 21q21 (74%), 6q16 (72%), 3p12 (66%), 8p24-8p21 (66%), 9p21 (64%), 11q22 (64%), and 14q13-14q21 (64%). Further frequent over-representation was found on 7q12-7q11.2 (75%), 16p11-16p12 (70%), 19p13 (70%), 9q34 (67%), 19q13 (67%), 13q34 (64%), 13q13 (64%), 17q21 (59%), 22q11 (61%), 8q24 (57%), and 1q21 (57%). Pronounced DNA gains and losses being defined as regions in which the ratio profiles exceeded the values of 1.5 and 0.5, respectively, frequently colocalized with peaks of incidence curve. The use of difference histograms for the comparison of tumor subgroups as well as case-by-case histogram for the analysis of 15 paired tumor samples identified several of the above alterations as relevant for tumor progression and metastasis formation. The study identified additional loci and delineates more precisely those that have been previously reported. For comparative purposes, we have made our primary data (ratio profiles, clinicopathological parameters, histograms) available at the interactive web site http://amba.charite.de/cgh, where the incidence of changes can be determined at individual loci and additional parameters can be applied for the analysis of our CGH results.

Carcinoma↗

PubMed2002

Overexpression of c-erbB-2 protein correlates with chromosomal gain at the c-erbB-2 locus and patient survival in advanced colorectal carcinomas.

Overexpression of the c-erbB-2 protein (also called HER-2/neu) is observed in a variety of malignancies including colorectal cancer (CRC). In this study we aimed to evaluate the rate of c-erbB-2 overexpression in our tumor collection and to clarify its correlation with the chromosomal status at the c-erbB-2 locus in CRC. Additionally we correlated the c-erbB-2 overexpression and the chromosomal gain of 17q with patient survival. Seventy-four specimens were analyzed immunohistochemically using a polyclonal c-erbB-2 antibody (DAKO) and the staining was scored according to the Clinical Trial Assay recommendations (0-3+). Of these, 45 cases were analyzed by comparative genomic hybridization (CGH) and immunohistochemistry (IHC). Overexpression was observed in 51% of the cases (score > or = 2). Chromosomal gains at the c-erbB-2 locus were clearly correlated with overexpression of the gene (P = 0.0009). Furthermore Kaplan-Meier analysis showed that overexpression of c-erbB-2 was significantly associated with poor survival and thus could serve as a prognostic marker. We conclude that c-erbB-2 is related with tumor progression in CRC which can be observed on protein level and reflects chromosomal gain at the locus at 17q.

Allelic Imbalance↗

PubMed2002

Mucosal flora in inflammatory bowel disease.

BACKGROUND & AIMS: Microorganisms that directly interact with the intestinal mucosa are obscured by fecal flora and poorly characterized. METHODS: We investigated the mucosal flora of washed colonoscopic biopsies of 305 patients with bowel inflammation and 40 controls. The microbial cultures were validated by quantitative polymerase chain reaction with subsequent cloning and sequencing, fluorescence in-situ hybridization, and electron microscopy. RESULTS: We found high concentrations of mucosal bacteria in patients with bowel inflammation, but not in controls. The concentrations of mucosal bacteria increased progressively with the severity of disease, both in inflamed and non-inflamed colon. In patients with >10,000 cfu/microL, a thick bacterial band was attached to the intact mucosa without signs of translocation. Patients with inflammatory bowel disease (IBD) and concentrations of mucosal bacteria >50,000 cfu/microL had characteristic inclusions of multiple polymorphic bacteria within solitary enterocytes located next to the lamina propria, without or having no contact with the fecal stream. The identified bacteria were of fecal origin. CONCLUSIONS: Our findings suggest that the changes in the mucosal flora in IBD are not secondary to inflammation, but a result of a specific host response. We hypothesize that the healthy mucosa is capable of holding back fecal bacteria and that this function is profoundly disturbed in patients with IBD.

Adolescent↗

PubMed2002

Genetic alterations in epithelial ovarian tumors analyzed by comparative genomic hybridization.

The genetic changes involved in the pathogenesis of ovarian carcinoma are not completely understood. To investigate this matter, we studied paraffin-embedded, microdissected tissue of 47 ovarian epithelial tumors (9 adenomas, 11 tumors of low malignant potential [LMP], 14 serous carcinomas, and 13 nonserous carcinomas) using comparative genomic hybridization (CGH). (The primary data used in this study are available at our CGH online tumor database at http://amba.charite.de/cgh.) Chromosomal imbalances were found in 1 serous adenoma and in 7 LMP tumors. In the latter the alterations appeared randomly and showed no overlap with alterations found in invasive carcinomas. Although the mean aberration number of low-grade serous carcinomas was comparable to LMP tumors, the imbalances of the former occurred with high incidence (>50%) and were found at different localizations. High-grade serous carcinomas had more than twice as much chromosomal imbalances as low-grade serous carcinomas and also had pronounced alterations. In serous carcinomas, gains were found on 3q, 6p, 7, 8q, and 20, and losses were found on 4q, 6q, 12q, 13q, and 16q. Comparing serous and nonserous carcinomas, the mean aberration number was comparable, but the number of high incidence changes was lower, and the most frequent imbalances were losses on 13q and gains on 20p. Overlapping alterations occurring in serous and nonserous carcinomas were gains on 3q and 6p, as well as losses on 4q. Chromosomal imbalances associated with poor prognosis of ovarian carcinomas were gains on 6p, 7q, and 13q and losses on 15q, 17p, 18q, and 21q. Our data indicate that serous LMP tumors and invasive carcinomas have different genetic aberrations, indicating that invasive carcinomas do not arise from preexisting serous LMP tumors. On the other hand, there are common genetic abnormalities in serous and nonserous carcinomas, suggesting that they have very early lesions in common but take different paths of further development.

Adenoma↗

PubMed2002

CD10 expression in non-small cell lung cancer.

CD10 is a cell surface endopeptidase that inactivates various potentially growth stimulatory peptides. In lung cancer cell lines this downregulation has been associated with increased proliferation. Downregulation of CD10 in lung cancer tissue is described, suggesting a potential role in carcinogenesis and a possible use of CD10 as a prognostic marker. We aimed to determine the rate of CD10 expression in our non-small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters and patient survival. 114 NSCLC were analysed immunohistochemically using a monoclonal CD10 antibody (clone NCL-CD10-270) on an NSCLC tissue micro array. The staining was semiquantitatively scored. CD10 expression was observed in 19% of cases, without any significant association with tumour type, -size, -grading, nodal status, clinical stage, and patient survival time. We conclude that a diagnostic use of CD10 immunostaining in NSCLC is unlikely.

Adenocarcinoma↗

PubMed2001

Immunohistochemical double-staining of renal allograft tissue: critical assessment of three different protocols.

Quantitative analyses of renal allograft tissue using immunohistochemical double-staining could be a useful tool to extend the existing knowledge on renal allograft immunopathology. Due to technical reasons, this method has been only rarely applied in the past. The use of indirect immunohistochemistry for double-staining bears the risk of nonspecific cross reactions between the two staining sequences. To date, various procedures have been refined to avoid such cross reactions. Here we assessed the validity of three different protocols for indirect immunohistochemical double-staining on frozen sections of renal transplant biopsies ( n=12). Both colocalized antigens and antigens with a non-overlapping distribution were stained according to each of the three protocols. Differentiation between the two staining sequences was achieved by employing different colored substrates of alkaline phosphatase (protocol 1), different enzymes (peroxidase and alkaline phosphatase) together with the use of 3,3'-diaminobenzidine-tetrahydrochloride substrate in the first staining sequence (protocol 2), or primary antibodies from different species (protocol 3). Sensitivity and specificity of each protocol were determined by quantitative comparison with control single-stainings of adjacent sections. Sensitivity of the first staining sequence was about 100% with each of the three protocols investigated. In the second staining sequence, sensitivities of protocols 1 (50%) and 2 (54-66%) were much lower than of protocol 3 (100%). Specificity of the second staining sequence was only 44% with protocol 1 compared with 98% with protocol 2 and 100% with protocol 3. In conclusion, protocols 1 and 2 are not recommended for quantitative double-staining analyses. In contrast, protocol 3 provided maximum sensitivity and specificity, even for antigens that are colocalized on the same cell type. Thus, the use of primary antibodies from different species is by far the most reliable technique for quantitative double-staining analyses in renal allograft tissue.

Antigens, CD↗

PubMedDate not supplied

Chromosomal alterations during lymphatic and liver metastasis formation of colorectal cancer.

Comparative genomic hybridization (CGH) was used to screen colorectal carcinomas for chromosomal aberrations that are associated with metastatic phenotype. In total, 63 tumor specimens from 40 patients were investigated, comprising 30 primary tumors, 22 systemic metastases (12 liver, 6 brain, and 4 abdominal wall metastases) and 11 lymph node tumors. Using statistical analysis and histograms to evaluate the chromosomal imbalances, overrepresentations were detected most frequently at 20q11.2-20q13.2, 7q11.1-7q12, 13q11.2-13q14, 16p12, 19p13, 9q34, and 19q13.1-19q13.2. Deletions were prominent at 18q12-18q23, 4q27-4q28, 4p14, 5q21, 1p21-1p22, 21q21, 6q16-6q21, 3p12, 8p22-8p23, 9p21, 11q22, and 14q13-14q21. Hematogenous metastases showed more alterations than lymph node tumors, particularly more deletions at 1p, 3, 4, 5q, 10q, 14, and 21q21 and gains at 1q, 7p, 12qter, 13, 16, and 22q. Comparing liver metastases with their corresponding primary tumors, particularly deletions at 2q, 5q, 8p, 9p, 10q, and 21q21 and gains at 1q, 11, 12qter, 17q12-q21, 19, and 22q were more often observed. The analysis suggested that the different pathways of tumor dissemination are reflected by a nonrandom accumulation of chromosomal alterations with specific changes being responsible for the different characteristics of the metastatic phenotype.

Chromosome Aberrations↗

PubMedDate not supplied

Identification of differentially expressed genes in classical and atypical multidrug-resistant gastric carcinoma cells.

The phenomenon of multidrug resistance (MDR) in human cancers is the major cause of failure of chemotherapy. To better understand the molecular events associated with the development of different types of MDR, a classical MDR P-glycoprotein expressing gastric carcinoma cell line and an atypical MDR P-glycoprotein-negative variant were analyzed by cDNA array hybridization. Of 588 cDNAs spotted on the array, a total of 9 genes showed differences in mRNA expressions. An enhanced expression level of 3 genes could be detected in both different MDR models (HLH, IR21, CCT5, Tx P-1), 4 genes were overexpressed solely in classical MDR cells (Hsp27, Rcl, aldehyde dehydrogenase 1, vimentin), whereas the expression of one gene was increased in atypical MDR cells (ProTa). Furthermore, the mRNA expressions of 3 genes were down-regulated in atypical MDR cells (Hsp27, vimentin, JNK2), whereas a decrease in mRNA expression in classical MDR cells could be determined for none of them. These differences were confirmed by a semiquantitative RT-PCR approach. Further characterization of these factors may provide more insight into the biology and development of different types of MDR in human gastric carcinomas. Moreover, these genes may be potential candidate factors for the diagnostics and/or prognosis of clinical drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Melorheostosis with ipsilateral nevus sebaceus (didymosis melorheosebacea).

We report an unusual case of unilateral melorheostosis and ipsilateral extensive sebaceous nevus. Because the two conditions affected the same side of the body, we hypothesize that they originated from a common genetic mechanism. The temporal and spatial co-occurrence may represent a further example of non-allelic didymosis (twin spotting). The embryo would carry two different recessive mutations at one gene locus or at linked loci on either of a pair of homologous chromosomes. Postzygotic recombination occurring during early embryonic development would result in two different populations of cells homozygous for either mutation. If this concept holds true, the present case may be described as " didymosis melorheosebacea ".

Adult↗

PubMedDate not supplied

Lack of HER-2/neu overexpression in non-Hodgkin's lymphoma.

OBJECTIVES: The HER-2/neu oncogene is overexpressed in many types of cancer and especially in 25% to 30% of breast cancers. Single reports mention HER-2/neu positivity in hematological malignancies like Hodgkins's disease and even diffuse large-cell lymphoma. OBJECTIVE: To test for HER-2/neu overexpression in patients with non-Hodgkin's lymphoma and the possible role of the recombinant monoclonal anti-HER-2/neu antibody trastuzumab (Herceptin) in the treatment of non-Hodgkin's lymphoma. MATERIALS AND METHODS: Serum samples from 87 consecutive unselected patients with non-Hodgkin's lymphoma were retrospectively retrieved from a serum bank and tested for the shed antigen of HER-2/neu using the Oncogene Sciences ELISA assay (Cambridge, MA, USA). From those lymphoma patients, the paraffin-embedded lymph-node specimens of 25 cases with diffuse large-cell lymphoma were stained with the HER-2/neu DAKO HercepTest. RESULTS: In 87 lymphoma patients, the serum level of HER-2/neu ranged from 3.6 to 244.1 ng/ml (median 8.0 ng/ml). Only 2 patients showed a marginal or increased HER-2/neu level with 15 ng/ml (which is the upper limit of normal) and 244.1 ng/ml, respectively. No patient with diffuse large-cell lymphoma showed HER-2/neu overexpression by immunhistochemistry of the lymph node. The paraffin block of the one patient with a very high HER-2/neu serum level was also stained for HER-2/neu overexpression. In this patient, suffering from a high-grade T-cell non-Hodgkin's lymphoma, no staining could be found. CONCLUSION: HER-2/neu is not overexpressed in non-Hodgkin's lymphoma and especially not in diffuse large-cell lymphoma, using a standardized immunochemistry technique with complementary serum testing. Thus, specific anti-HER-2/neu-targeted therapy should play no role in the treatment of non-Hodgkin's lymphoma.

Adolescent↗

PubMedDate not supplied

CD24 expression is specific for tamoxifen-resistant ductal breast cancer cases.

BACKGROUND: In breast cancer, the expression of CD24 represents a poorly recognised unfavourable prognostic factor. CD24 has been described to be potentially down-regulated by estrogen receptor alpha (ER). The present study was aimed at examining the predictive value of CD24 expression in tamoxifen-treated breast cancer cases. MATERIALS AND METHODS: Sixty patients with primary invasive ductal breast cancers with post-operative tamoxifen treatment were enrolled in the study. Immmunohistochemical reactions were performed using monoclonal antibodies directed against CD24 and ER. RESULTS: Cases demonstrating cytoplasmic-membranous expression of CD24 (CD24c-m) proved to be characterised by a significantly lower expression of ER as compared to CD24c-m-negative cases. A multivariate progression analysis based on the Cox proportional hazard model demonstrated that CD24c-m expression is an independent prognostic factor for poor overall survival. CONCLUSION: The data from the present study suggested that CD24c-m expression is specific for tamoxifen-resistant breast cancer cases. CD24 should be subjected to comprehensive studies as a marker of resistance to tamoxifen treatment.

Antineoplastic Agents, Hormonal↗

PubMedDate not supplied

Comparative promoter analysis of doxorubicin resistance-associated genes suggests E47 as a key regulatory element.

Working under the assumption that up- or downregulation of genes implicated in chemoresistance may be the result of altered function of regulatory transcription factors (TF), over-represented TF-binding sites of gene lists previously associated with doxorubicin resistance were the target of our search. First, a data warehouse was set up containing 52 genes which were present in at least two gene lists; of those, proximal promoter sequences (1 kb upstream and 0.05 kb downstream of the transcriptional start sites) could be retrieved from genomic databases for 45 genes using the EZ-Retrieve. The TOUCAN tool MotifScanner, which searches the TRANSFAC database, was used to detect TF-binding sites (TFBSs) in our set of sequences. The statistics tool of the Java program TOUCAN was applied to the data with the appropriate expected frequencies file to compare the measured prevalence to a background model. The most significantly over-represented TFBS was that of E47 (p=0.00024, prevalence: 0.2 vs. background: 8.19E-6). In summary, based on the results of our analysis it is hypothesized that the E47 transcription factor may contribute to doxorubicin resistance.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

CD46 expression is indicative of shorter revival-free survival for ovarian cancer patients.

BACKGROUND: The membrane cofactor protein CD46 represents a complement inhibitor, which protects autologous cells from complement - mediated cytotoxicity. CD46 may exhibit the potential to protect tumor cells from the immune responses of the host. The present study aimed to evaluate the prognostic significance of CD46 expression in ovarian cancers. MATERIALS AND METHODS: The analyses were performed on 73 ovarian cancer samples. Immunohistochemical reactions were performed on paraffin sections of tumors using monoclonal antibodies directed against CD46. The immunohistochemical reactions and the clinical observations results were subjected to statistical analysis. RESULTS: Expression of CD46 was demonstrated in 60% of primary laparotomy cases and in 70% secondary cytoreduction cases. Kaplan-Meier analysis showed that a significantly shorter revival-free time was linked to cases with CD46 expression at PL (p= 0.01). CONCLUSION: Ovarian cancers manifest CD46 expression that is linked to a less favourable prognosis.

Female↗