Biomedical subjects

Manfred Dietel

Publications and source records attributed to Manfred Dietel.

At least 55 records · Page 3Linked to original sources

PubMed2005

Immunoprofiles of 11 biomarkers using tissue microarrays identify prognostic subgroups in colorectal cancer.

BACKGROUND AND AIMS: Genomewide expression profiling has identified a number of genes expressed at higher levels in colorectal cancer (CRC) than in normal tissues. Our objectives in this study were: 1) to test whether genes were also distinct on the protein level; 2) to evaluate these biomarkers in a series of well-characterized CRCs; and 3) to apply hierarchical cluster analysis to the immunohistochemical data. METHODS: Tissue microarrays (TMAs) comprising 351 CRC specimens from 270 patients were constructed to evaluate the genes Adam10, Cyclin D1, Annexin II, NFKB, Casein kinase 2 beta (CK2B), YB-1, P32, Rad51, c-fos, IGFBP4, and Connexin26 (Cx26). In total, 3,797 samples were analyzed. RESULTS: Unsupervised hierarchical clustering discovered subgroups of CRC that differed by tumor stage and survival. Kaplan-Meier analysis showed that reduced Cx26 expression was significantly associated with shorter patient survival and higher tumor grade (G1/G2 vs G3, P = .02), and Adam10 expression with a higher tumor stage (pT1/2 vs pT3/4, P = .04). CONCLUSIONS: Our study highlights the potential of TMAs for a higher-dimensional analysis by evaluating serial sections of the same tissue core (three-dimensional TMA analysis). In addition, it endorses the use of immunohistochemistry supplemented by hierarchical clustering for the identification of tumor subgroups with diagnostic and prognostic signatures.

Biomarkers, Tumor↗

PubMed2005

Prognostic value of immunohistochemical estimation of CD24 and Ki67 expression in cisplatin and paclitaxel treated ovarian carcinoma patients.

CD24 is a small membranous protein which may participate in invasion of tumor cells. Present study aimed at evaluation of prognostic significance linked to immunohistochemical demonstration of CD24 expression and the proliferation index, Ki67 expression in ovarian cancers. The immunohistochemical reactions with monoclonal CD24- and Ki67-specific antibodies were performed in paraffin sections originating from 30 patients with ovarian cancer treated using cisplatin and paclitaxel. Results of the reactions and analysis of the clinical course of the patients were subjected to statistical analysis. Cases with cytoplasmic-membranous expression of CD24 (CD24c-m) were found to exhibit significantly shorter overall survival time (P = 0.0002) and progression-free period (P = 0.0005). Cases with membranous expression of CD24 (CD24m) manifested a longer overall survival time (P = 0.022). No relationship was disclosed between expression of Ki67 on the one hand and survival time and CD24 expression on the other. As documented using chi square test, expression of CD24c-m predisposed to relapses (P = 0.012), progression (P = 0.0362) and to death (P = 0.0034). Deaths were encountered significantly less frequently in cases with CD24m expression (P = 0.0465). The studies demonstrated that CD24c-m represented a strongly unfavorable prognostic indicator. The antigen represents an interesting target in the search for novel therapeutic methods. The more aggressive course of cases with CD24c-m expression was not linked to more intense proliferation of the tumor cells.

Antigens, CD↗

PubMed2004

Steroid administration before partial hepatectomy with temporary inflow occlusion does not influence cyclin D1 and Ki-67 related liver regeneration.

BACKGROUND AND AIMS: If temporary inflow occlusion is required during liver resection, the postoperative course might be complicated by ischaemia-reperfusion injury. Steroids protect against ischaemia-reperfusion injury; however, due to its anti-proliferative character concerns exist on its use on liver regeneration after resection. We investigated the effects of methylprednisolone on hepatocyte proliferation after partial hepatectomy with temporary inflow occlusion. PATIENTS AND METHODS: Prior to surgery, one group of Wistar rats received methylprednisolone, while a second group served as non-treated controls. Ischaemia-reperfusion injury was indicated by AST, ALT, and GLDH at 6 h after surgery. Immunohistochemistry tools were used to determine the mitotic index and Ki-67 expression, while cyclin D1 expression characterized the proliferative activity on days 1, 4, 7, and 10. RESULTS: The post-ischaemic liver enzyme release had significantly decreased in the methylprednisolone group, while expression of cyclin D1, percentage of Ki-67-positive cells, and mitotic cell index were comparable in both groups. Similar results were found for bilirubin and albumin and for weight of proliferating liver. CONCLUSION: Although steroid administration significantly reduced ischaemia-reperfusion-associated tissue injury, it has no apparent effects on hepatic regeneration. Thus, steroids could be recommended if a temporary liver ischaemia is required during surgery, in order to reduce complications caused by severe ischaemia-related organ dysfunction.

Animals↗

PubMed2004

Expression of the ELAV-like protein HuR is associated with higher tumor grade and increased cyclooxygenase-2 expression in human breast carcinoma.

PURPOSE: The human ELAV (embryonic lethal abnormal vision)-like protein HuR stabilizes a certain group of cellular mRNAs that contain AU-rich elements in their 3'-untranslated region. Cell culture studies have shown that the mRNA of cyclooxygenase (COX)-2 can be stabilized by HuR. EXPERIMENTAL DESIGN: To investigate a possible contribution of dysregulation of mRNA stability to the progression of cancer and to overexpression of COX-2, we studied expression of HuR in 208 primary breast carcinomas by immunohistochemistry. RESULTS: There were two different staining patterns of HuR in tumor tissue of breast carcinomas: nuclear expression was seen in 61% of cases; and an additional cytoplasmic expression was seen in 30% of cases. Expression of HuR was significantly associated with increased COX-2 expression; this association was particularly significant for cytoplasmic HuR expression (P < 0.0005). We further observed a significant association of cytoplasmic (P = 0.002) or nuclear HuR (P = 0.027) expression with increased tumor grade. Only 13% of the grade 1 carcinomas showed cytoplasmic expression of HuR, compared with 46% of the grade 3 carcinomas. There was no significant correlation between HuR expression and other clinicopathological parameters such as histological type, tumor size, or nodal status as well as patient survival. CONCLUSIONS: Our results suggest that overexpression of HuR in tumor tissue may be part of a regulatory pathway that controls the mRNA stability of several important targets in tumor biology, such as COX-2. Based on our results, additional studies are necessary to investigate whether HuR might be a potential target for molecular tumor therapy.

Analysis of Variance↗

PubMed2004

Cytomegalovirus is not associated with progression and metastasis of colorectal cancer.

Recently, it was hypothesized that human cytomegalovirus (HCMV) might be associated with colorectal cancer progression. However, the role of HCMV infection in colorectal cancer remains controversial. We aimed to assess whether nucleic acids and/or gene products of HCMV could be detected in primary and metastatic colorectal carcinomas. Fresh-frozen biopsy specimens from 77 primary and metastatic colorectal carcinomas of randomly selected patients were analyzed by PCR and immunohistochemistry. We investigated 57 primary tumors and 20 metastases, comprising 13 tumor pairs from the same patient. In PCR, four primary tumors showed a positive CMV result whereas all investigated metastases were negative including three paired samples from positive primaries. In immunohistochemistry, no specific staining could be determined in all neoplastic epithelial cells. In summary, we think that there is no association between CMV infection and tumor progression or metastasis formation of colorectal cancer.

Carcinoma↗

PubMed2004

Polo-like kinase 1 is overexpressed in prostate cancer and linked to higher tumor grades.

BACKGROUND: Polo-like kinase 1 (PLK1) is known to be one of the key players in the regulation of mitosis of both normal and malignant transformed cells. Moreover, several studies reported an overexpression of PLK1 in human malignancies compared to the corresponding tissue of origin. METHODS: In this study, expression of PLK1 was investigated by immunohistochemistry in 78 tissue specimens of prostate carcinoma and in adjacent normal prostate tissue as well as in benign prostate hyperplasia. PLK1 expression was semiquantitavely scored and subsequently correlated to clinicopathological parameters and patient prognosis. RESULTS: No significant PLK1 expression was observed in normal prostate glandular epithelium and stroma. Specimens of benign prostate hyperplasia were PLK1-negative as well. In contrast, 52.6% of all prostate carcinomas showed strong expression of PLK1. High grade intraepithelial lesions, if present, stained almost invariably in the same manner as the respective invasive tumors. Expression of PLK1 correlated positively with Gleason grade (P = 0.011). No other significant correlations of PLK1 expression with either tumor stage, WHO tumor grade, preoperative PSA, age, or resection margins could be established. In an analysis for differences in PSA-relapse-free survival time, PLK1 expression was not a prognostic marker. CONCLUSIONS: These results demonstrate a high rate of PLK1-positivity in prostate cancer which suggests involvement of PLK1 in tumorigenesis and progression in this tumor entity. Therefore, targeted strategies focussing on PLK1 inhibition might represent a promising new chemotherapeutic approach in prostate cancer.

Aged↗

PubMed2004

Expression of CD24 in adenocarcinomas of the pancreas correlates with higher tumor grades.

BACKGROUND/AIMS: CD24 is expressed in hematological malignancies as well as in a large variety of solid tumors and is often associated with a more aggressive course of the disease. We aimed to evaluate CD24 protein expression in pancreatic adenocarcinomas and to correlate it to clinicopathological data including patient survival. METHODS: 95 primary adenocarcinomas of the pancreas were immunostained using a monoclonal CD24 antibody (Ab-2, clone 24C02). Staining was evaluated as negative versus positive for statistical analysis. RESULTS: CD24 expression was observed in 71.6% of cases with a heterogeneous distribution, and a significantly higher rate of positivity in high grade (G3) tumors. In univariate survival analyses, no association of CD24 expression with shortened overall survival of the patients could be demonstrated. CONCLUSION: CD24 is commonly expressed in adenocarcinomas of the pancreas, preferentially high-grade tumors and thus might be a marker of disease progression.

Adenocarcinoma↗

PubMed2004

CD24 expression is a significant predictor of PSA relapse and poor prognosis in low grade or organ confined prostate cancer.

BACKGROUND: The prognostic impact of tumor grading and staging is markedly reduced in organ confined or moderately differentiated prostate cancer, which underscores the importance of new prognostic markers. Evaluating public expression data of prostate cancer, we found an upregulation of the candidate gene CD24. METHODS: We examined immunohistochemically the expression of CD24 protein in 31 nodal metastases and 102 adenocarcinomas of the prostate and correlated our findings to clinicopathological parameters. RESULTS: CD24 expression was found in 48% of primary prostate cancer cases and in 68% of lymph node metastases. Kaplan Meier curves and Cox regression analysis showed that CD24 expression was strongly linked to significantly earlier disease progression (relative risk = 3.2), which was especially pronounced in organ confined, or moderately differentiated primary prostate tumors. CONCLUSIONS: We conclude that CD24 is an important prognostic tissue marker for prostate cancer which could help to define patients of low or high risk of recurrence.

Adenocarcinoma↗

PubMed2004

Overexpression of cyclooxygenase-2 correlates with chromosomal gain at the cyclooxygenase-2 locus and decreased patient survival in advanced colorectal carcinomas.

PURPOSE: Overexpression of cyclooxygenase-2 is observed in a variety of malignancies including colorectal cancer. However, to date, cyclooxygenase-2 expression by advanced human colorectal cancers and their metastases has been poorly characterized. This study was designed to evaluate the rate of cyclooxygenase-2 overexpression in our tumor collection and to clarify its correlation with the chromosomal status at the cyclooxygenase-2 locus in colorectal cancer. METHODS: Seventy-four specimens were analyzed immunohistochemically using a monoclonal cyclooxygenase-2 antibody. The staining was scored semiquantitatively as: -, negative; +, weak; ++, moderate; and +++, strong positive. Of these, 45 specimens were analyzed using comparative genomic hybridization and immunohistochemistry. We correlated the cyclooxygenase-2 overexpression with the chromosomal gain of 1q25.2-q25.3 and patients survival and compared primary colorectal cancers and their paired metastases at the DNA and protein level. RESULTS: Overexpression was observed in 58 percent of the cases (score > or = ++). Chromosomal gains at the cyclooxygenase-2 locus were clearly correlated with overexpression of the gene (P=0.009). Furthermore, the comparison of paired tumor samples showed additional overrepresentation in the metastases at the cyclooxygenase-2 locus, which could be confirmed by immunohistochemistry. Kaplan-Meier analysis showed that overexpression of cyclooxygenase-2 was significantly associated with poor survival and thus could serve as a prognostic marker. CONCLUSIONS: We conclude that cyclooxygenase-2 is related with tumor progression and metastasis in colorectal cancer, which can be observed on protein level, and reflects chromosomal gain at the locus at 1q25.2-q25.3.

Chromosome Aberrations↗

PubMed2004

Overexpression of the embryonic-lethal abnormal vision-like protein HuR in ovarian carcinoma is a prognostic factor and is associated with increased cyclooxygenase 2 expression.

The human embryonic-lethal abnormal vision-like protein HuR is involved in the regulation of mRNA turnover and serves as a shuttling protein between the nucleus and the cytoplasm that stabilizes mRNAs containing adenine- and uridine-rich elements in their 3' untranslated region. We have shown recently that expression of cyclooxygenase (COX)-2 is related to poor prognosis in ovarian carcinoma. Other studies have shown that the COX-2 mRNA contains an adenine- and uridine-rich element and is stabilized by HuR. In this study, we investigated the expression and cellular distribution of HuR in 83 primary ovarian carcinomas, 16 borderline tumors of the ovary, 3 normal ovaries, and 9 ovarian carcinoma cell lines. Expression of HuR was detected in all cell lines on the mRNA and protein level and showed a predominantly nuclear staining in OVCAR-3 cells by confocal microscopy. In an immunohistochemical evaluation of human ovarian carcinomas, HuR showed a nuclear expression in 81% of tumors. In addition, a cytoplasmic expression of HuR was observed in a subgroup of 45% of ovarian carcinomas. Nuclear as well as cytoplasmic expression of HuR was significantly increased in ovarian carcinomas compared with borderline tumors or normal ovaries. In univariate analysis, a significant association between cytoplasmic HuR expression and increased COX-2 expression (P = 0.025) as well as between histological grade (P = 0.008) and mitotic activity (P = 0.002) was observed, although nuclear expression of HuR was not correlated with COX-2 expression or other clinicopathological parameters. In Kaplan-Meier survival analysis, increased cytoplasmic expression of HuR was a significant prognostic indicator for progression-free survival (P = 0.03) as well as overall survival (P = 0.007). In multivariate analysis using the Cox regression model, cytoplasmic expression of HuR was an independent prognostic parameter for reduced overall survival with a relative risk of 2.62 (95% confidence interval, 1.32-5.19). Our results suggest that there is a dysregulation of cellular distribution of the mRNA stability factor HuR in a subset of invasive ovarian carcinomas. This dysregulation appears to result in an increased expression of COX-2, an increased proliferative rate, and may lead to a reduced survival time. Additional studies are required to analyze the downstream effects of increased cytoplasmic expression of HuR. In addition, it would be interesting to investigate the prognostic role of increased cytoplasmic expression of HuR in prospective studies.

Analysis of Variance↗

PubMed2004

Multidrug-resistant cancer cells facilitate E1-independent adenoviral replication: impact for cancer gene therapy.

Resistance to chemotherapy is responsible for a failure of current treatment regimens in cancer patients. We have reported previously that the Y-box protein YB-1 regulates expression of the P-glycoprotein gene mdr1, which plays a major role in the development of a multidrug resistant-tumor phenotype. YB-1 predicts drug resistance and patient outcome in breast cancer. Thus, YB-1 is a promising target for new therapeutic approaches to defeat multidrug resistance. In drug-resistant cancer cells and in adenovirus-infected cells YB-1 is found in the nucleus. Nuclear accumulation of YB-1 in adenovirus-infected cells is a function of the E1 region, and we have shown that YB-1 facilitates adenovirus replication. Here we report that E1A-deleted or mutant adenovirus vectors, such as Ad312 and Ad520, replicate efficiently in multidrug-resistant (MDR) cancer cells and induce an adenovirus cytopathic effect resulting in host cell lysis. Thus, replication-defective adenoviruses are a previously unrecognized vector system for a selective elimination of MDR cancer cells. Our work forms the basis for the development of novel oncolytic adenovirus vectors for the treatment of MDR malignant diseases in the clinical setting.

Adenovirus E1A Proteins↗

PubMed2004

Array technology and proteomics in autoimmune diseases.

Two new technologies (tissue microarrays (TMAs) and proteomics) have generated a great amount of data in life science. High-density TMAs allow for the simultaneous analysis of proteins and RNA by various methods (immunohistochemistry, in situ hybridization, FISH) on a large scale and under highly standardized conditions. Proteomics includes a variety of techniques that are partly high throughput. These techniques aim at the innovation of proteins, the description of the domain structure, the determination of protein sequences and epitope characterization, and ultimately the definition of protein function and protein reactivities in immunologic processes. Proteins that have been characterized accordingly require validation mostly at the morphologic level of defined tissue, linking proteomics to TMAs. In autoimmune diseases, array-based antigenic fingerprinting of autoantibodies will drive the development and the selection of antigen-specific diagnostic tools and therapies. The powerful combination of genomics and proteomics formed in tissue arrays has the potential to change the way the biology of autoimmunity is studied. Novel targets of drug discovery, based on antigen-specific therapies to induce anergy, or regulatory T-cells using the targeted autoantigens of individual patients could be developed in the coming decades.

Autoimmune Diseases↗

PubMed2004

Ischemic preconditioning and methylprednisolone both equally reduce hepatic ischemia/reperfusion injury.

BACKGROUND: Ischemic preconditioning (I/P) and methylprednisolone (MP) have been suggested to protect against ischemia-reperfusion (IR) injury, which results in an increased tolerance against organ hypoxia. METHODS: Before 45 minutes of hepatic ischemia, male Wistar rats were pretreated with either I/P (5/30 minutes) or MP (30 mg/kg BW). The degree of IR injury and the postischemic inflammatory (leukocyte infiltration, myeloperoxidase, intercellular adhesion molecule-1) and apoptotic (TUNEL, caspase 3, cytochrome C) activity was measured in both groups and compared with non-pretreated (ischemic) animals. RESULTS: Histology and enzyme release revealed that I/P and MP treatment provided significant protection as compared with ischemic controls. TUNEL-positive cells, as well as caspase 3 and cytochrome C expression, were clearly reduced in hepatic tissue of MP-treated animals and partially reduced in I/P-treated animals when compared with ischemic animals. The inflammatory response was considerably reduced in MP- and I/P-treated animals, especially in the early period after ischemia. NF-kappaB/Rel-binding activity was increased after I/P and decreased in MP-treated animals, whereas ischemic controls showed a constant binding activity. CONCLUSIONS: MP (probably by downregulation of NF-kappaB-binding activity) and I/P attenuated the postischemic apoptotic and inflammatory response. Both treatments equally reduced IR-related hepatocellular damage, and, thus, may also be applied equally in surgery involving warm organ hypoxia.

Animals↗

PubMed2003

CD24 expression is a new prognostic marker in breast cancer.

PURPOSE: CD24 is expressed in hematological malignancies as well as in a large variety of solid tumors including breast cancer. We aimed to evaluate CD24 protein expression in breast cancer and to correlate to clinicopathological data including patient survival. EXPERIMENTAL DESIGN: Primary breast carcinomas (201) with a mean clinical follow-up time of 53 months were immunostained using a monoclonal CD24 antibody (Ab-2, clone 24C02). The staining was evaluated as negative versus positive for statistical analysis. RESULTS: In invasive breast carcinomas, CD24 expression was observed in 84.6% of cases. In univariate survival analyses, a significant association of CD24 expression with shortened patient overall survival (5-year survival rate 91.9% versus 83.8%; P = 0.031; log rank test) and disease-free survival (5-year progression rate 88.3% versus 57.0%; P = 0.0008) was demonstrated. In multivariate analyses CD24, tumor grading and nodal status were significant prognostic parameters for shortened disease-free survival. CONCLUSIONS: Our data suggest that CD24 expression in primary breast cancer as detected by immunohistochemistry might be a new marker for a more aggressive breast cancer biology.

Aged↗

PubMed2003

YB-1 as a cell cycle-regulated transcription factor facilitating cyclin A and cyclin B1 gene expression.

Expression of the Y-box protein YB-1 is increased in proliferating normal and cancer cells, but its role in cell proliferation and cell cycle progression is unclear. We have identified a cell cycle-dependent relocalization of YB-1 from the cytoplasm to the nucleus at the G1/S phase transition and demonstrate that both the charged zipper and the cold shock domain are involved in regulating this process. Using cell lines that constitutively overexpress YB-1, we show that nuclear accumulation of YB-1 is associated with increased cyclin A and cyclin B1 mRNA and protein expression. We provide evidence that deregulated YB-1 expression is linked to adhesion-independent cell proliferation through the induction of cyclin A. Thus, we have identified YB-1 as a cell cycle stage-specific transcription factor important for cell proliferation.

Amino Acid Motifs↗

PubMed2003

ALCAM/CD166 is up-regulated in low-grade prostate cancer and progressively lost in high-grade lesions.

BACKGROUND: Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, including malignant melanoma, prostate cancer cell lines, and prostate cancer. We aimed to clarify the expression patterns of ALCAM in normal and malignant prostate tissue. METHODS: RNA from 54 matched pairs of microdissected prostate tissue (tumor and normal) was hybridized to a custom built 4K GeneChip. Frozen section immunohistochemistry was used to confirm the ALCAM expression. RESULTS: Chip-based transcript analysis revealed an up-regulation of ALCAM in prostate cancer in 22% of cases. Immunohistochemistry showed a focally raised ALCAM expression in 81% and a decreased expression in 19% of cases. These expression patterns correlated significantly with Gleason tumor grade: ALCAM up-regulation was found in most low-grade tumors (Gleason grade 1-3), whereas down-regulation occurred preferentially in high-grade tumors (Gleason grade 4 and 5), although up-regulation of ALCAM expression was preserved in two Gleason grade 5 tumors. CONCLUSION: ALCAM expression is commonly disturbed in prostate cancer, which might indicate a role of ALCAM in the progression of this disease.

Activated-Leukocyte Cell Adhesion Molecule↗

PubMed2003

Expression of the cell adhesion molecule CD146/MCAM in non-small cell lung cancer.

Expression of MCAM is observed in a variety of human malignancies. We aimed to determine the rate of MCAM expression in our non-small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters and patient survival. 85 NSCLC were analysed immunohistochemically using a monoclonal MCAM antibody (clone N1238) on an NSCLC tissue micro array. The staining was semiquantitatively scored. We found MCAM expression in 51% of NSCLC, preferentially squamous cell carcinomas (p=0.004). No other correlations to tumour size, grade, or stage were found. Univariate survival analysis showed no significant differences of MCAM positive and negative tumours. In adenocarcinomas however, MCAM positivity was significantly associated with shorter patient survival (p=0.016). We conclude, that MCAM is expressed in a high proportion of NSCLC and might be predictive of shortened patient survival in adenocarcinomas of the lung. Colour figure can be viewed on http://www.esacp.org/acp/2003/25-2/kristiansen.htm

Adenocarcinoma↗

PubMed2003

Protein kinase C isoform expression in ovarian carcinoma correlates with indicators of poor prognosis.

In this study expression of protein kinase C alpha (PKCalpha), delta (PKCdelta) and iota (PKCiota) was determined immunohistochemically in formalin-fixed paraffin-embedded tissue specimen of ovarian cystadenomas (n=7), borderline tumours of the ovary (n=8), primary (n=54) and recurrent invasive ovarian carcinomas (n=13). The expression was correlated with clinicopathological parameters and patient survival. In addition, expression of PKCiota was assessed in 3 ovarian carcinoma cell lines (OVCAR-3, SKOV-3, OAW-42) and in one human ovarian surface epithelium (HOSE) cell line. We found expression of PKCalpha in 71.4% of cystadenomas, 50% of borderline tumours, 53.7% of primary and 38.5% of recurrent ovarian carcinomas. PKCdelta was not expressed in epithelium of adenomas, borderline tumours, primary and recurrent ovarian carcinomas. PKCiota was expressed in 51.9% of primary and 46.2% of recurrent ovarian carcinomas but not in cystadenomas and borderline tumours of the ovary. Consistent with these findings ovarian carcinoma cell lines showed strong expression of PKCiota whereas HOSE cells did not. Correlation of PKCalpha and PKCiota expression and clinicopathological features revealed a significant negative correlation of PKCalpha with histopathological grading and a significant positive correlation of PKCiota with histopathological grading and FIGO stage as well as a borderline significant positive correlation with proliferation index. Univariate survival analysis showed that amongst other yet known prognostic parameters (FIGO stage, histopathological grading, proliferation index) PKCiota expression in primary ovarian carcinomas correlated significantly (p=0.024) with a reduced median survival time, but was not an independent prognostic factor. The findings of this study, together with data from functional studies by other groups suggest that alteration of PKC isoform expression may be involved in progression of ovarian carcinomas.

Carcinoma↗