Biomedical subjects

G B Kristensen

Publications and source records attributed to G B Kristensen.

At least 19 recordsLinked to original sources

PubMed2005

Markers of apoptosis in stage IB squamous cervical carcinoma.

AIMS: To examine the prognostic relevance of the expression of the Bcl-2, Bcl-xL, and Bax proteins in stage IB squamous cervical carcinoma (SCC). METHODS: In total, 220 patients who underwent radical hysterectomy and bilateral lymphadenectomy at the Norwegian Radium Hospital for stage IB SCC between 1987 and 1993 were studied. Immunohistochemistry using monoclonal antibodies against Bcl-2, Bcl-xL, and Bax was used to examine protein expression. Ten patients who underwent hysterectomy for uterine prolapse served as controls. RESULTS: Cytoplasmic expression of Bcl-2, Bcl-xL, and Bax was low (< 5% positive cells) in 159 of 220 (73%), 193 of 220 (87%), and 39 of 220 (18%) tumours, respectively, and high (> or = 5% positive cells) in 61 of 220 (27%), 27 of 220 (13%), and 181 of 220 (82%) tumours, respectively. In univariate analysis, all classic clinicopathological parameters but none of the investigated proteins were associated with prognosis. In multivariate analysis, only deep stromal invasion was independently related to survival. CONCLUSION: Bcl-2, Bcl-xL, and Bax were not independently associated with prognosis in stage IB SCC.

Adult↗

PubMed2004

TP53 mutations in early-stage ovarian carcinoma, relation to long-term survival.

We conducted the present study to evaluate the frequency and prognostic importance on long-term survival of TP53 mutations and TP53 protein accumulation in a cohort of 178 patients with early-stage ovarian carcinomas. TP53 mutations scored as aberrant temporal temperature gradient gel electrophoresis pattern from all exons were observed in 39.9% of the tumours. Full screening of exons 5-8, followed by sequencing, was successful in 135 cases, and 48 mutations altering the protein were detected in 39 cases (28.9%). TP53 mutations were slightly less common in the Federation of Gynecologists and Obstetricians stage IA than in IB/IC (P=0.05). No significant correlations with histological type, grade of differentiation, DNA ploidy status or age at diagnosis were found. TP53 protein accumulation analysed by immunohistochemistry was found in 32.6% of all tumours, and was a poor predictor of TP53 mutations with 56.4% sensitivity, 77.1% specificity, 50% positive predictive value and 81.3% negative predictive value. Neither TP53 mutations nor TP53 protein accumulation influenced the prognosis significantly in this group of patients.

Aged↗

PubMed2003

Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial.

BACKGROUND: Despite improvements in the treatment of ovarian cancer, most patients develop recurrent disease within 3 years of diagnosis. There is no agreed second-line treatment at relapse. We assessed paclitaxel plus platinum chemotherapy as such treatment. METHODS: In parallel international, multicentre, randomised trials, between January, 1996, and March, 2002, 802 patients with platinum-sensitive ovarian cancer relapsing after 6 months of being treatment-free were enrolled from 119 hospitals in five countries. Patients were randomly assigned paclitaxel plus platinum chemotherapy or conventional platinum-based chemotherapy. Analysis was by intention to treat, except for toxic effects. FINDINGS: With a median follow-up of 42 months, 530 patients have died. Survival curves showed a difference in favour of paclitaxel plus platinum (hazard ratio 0.82 [95% CI 0.69-0.97], p=0.02), corresponding to an absolute difference in 2-year survival of 7% between the paclitaxel and conventional treatment groups (57 vs 50% [95% CI for difference 1-12]), and median survival of 5 months (29 vs 24 months [1-11). 717 patients developed progressive disease or died. The progression-free survival curves show a difference in favour of paclitaxel plus platinum (hazard ratio 0.76 [0.66-0.89], p=0.0004), corresponding to an absolute difference in 1-year progression-free survival of 10% (50 vs 40% [4-15]) and in median progression-free survival of 3 months (13 vs 10 months [1-5]). INTERPRETATION: Paclitaxel plus platinum chemotherapy seems to improve survival and progression-free survival among patients with relapsed platinum-sensitive ovarian cancer compared with conventional platinum-based chemotherapy.

Aged↗

PubMed2003

Large-scale genomic instability predicts long-term outcome for women with invasive stage I ovarian cancer.

BACKGROUND: The objective was to evaluate the value of DNA ploidy using high-resolution image cytometry in predicting long-term survival of patients with early ovarian cancer. PATIENTS AND METHODS: A retrospective analysis of 284 cases with FIGO stage I ovarian carcinoma treated during the period 1982-1989 was performed. Clinical follow-up information was available for all patients. RESULTS: Patients with diploid and tetraploid tumors had a 10-year relapse-free survival of 95% and 89%, respectively, compared with 70% and 29% for polyploid and aneuploid tumors, respectively. DNA ploidy analysis was the strongest predictor of survival in multivariate analysis (diploid/tetraploid versus polyploid/aneuploid; relative hazard 9.0) followed by histological grade, including clear cell tumors in the group of poorly differentiated tumors (grade 1-2 versus grade 3 or clear cell; relative hazard 2.7), and FIGO stage (Ib/Ic versus Ia; relative hazard 2.0). In a stratified Kaplan-Meier analysis, patients with grade 1-2, diploid or tetraploid tumors had a 10-year relapse-free survival of 95%, forming a low-risk group. Patients with grade 3 or clear cell, diploid or tetraploid tumors had 10-year relapse-free survival of 86%, forming an intermediate-risk group, while all patients with aneuploid/polyploid tumors formed a high-risk group, with 10-year relapse-free survival of 34%. CONCLUSIONS: This study points to the importance of including DNA ploidy analysis by image cytometry when selecting patients with early ovarian cancer for adjuvant treatment after surgery.

Adult↗

PubMed2001

Histologic subtype has minor importance for overall survival in patients with adenocarcinoma of the uterine cervix: a population-based study of prognostic factors in 505 patients with nonsquamous cell carcinomas of the cervix.

BACKGROUND: The incidence of adenocarcinoma of the uterine cervix is increasing. For better prognostic information, the authors studied all nonsquamous cell carcinomas (non-SCCs) in the Norwegian population over a total of 15 years. METHODS: All non-SCCs from three 5-year periods (1966-1970, 1976-1980, and 1986-1990) were reviewed and classified according to the World Health Organization classification system, and histopathologic and clinical parameters were registered. Tissue blocks were available from all patients. RESULTS: Of 505 patients, 417 had tumors classified as adenocarcinoma, and 88 had tumors classified as other non-SCC. The mean ages were 53 years and 52 years for patients with adenocarcinoma and non-SCC, respectively. Sixty-two percent of the staged patients had clinical Stage I disease according to the classification system of the International Federation of Gynecology and Obstetrics (FIGO). In univariate analyses, histology, architectural and nuclear grade, extension to the vagina or corpus uteri, tumor length (> 20 mm) or tumor volume (> 3000 mm(3)), infiltration depth (in thirds of the cervical wall), thickness of the remaining wall (< 3 mm), vascular invasion, lymph node metastases, treatment, and patient age were significant variables in patients with FIGO Stage I disease. Variables with no significance in patients with Stage I disease were number of mitoses, state of resection margins, infiltration to ectocervix, tumor thickness, lymphoid reaction, earlier or concomitant cervical intraepithelial neoplasia, stump carcinoma, DNA ploidy or DNA index, or time period. Multivariate analyses of patients with FIGO Stage I disease identified small cell carcinoma, corpus infiltration, vascular invasion, and positive lymph nodes as independent prognostic factors. CONCLUSIONS: Small cell carcinoma was the only histologic subgroup of independent importance for prognosis in patients with non-SCC of the uterine cervix. No significant difference between major subtypes of adenocarcinoma favored a simplified classification. Extension to the corpus in patients with early-stage disease was of independent significance and should be acknowledged in planning treatment.

Adenocarcinoma↗

PubMed2001

Phase I/II trial of the multidrug-resistance modulator valspodar combined with cisplatin and doxorubicin in refractory ovarian cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) of doxorubicin when given in combination with cisplatin and the multidrug-resistance (MDR) modulator valspodar and the remission rate induced by this combination in patients with platinum- and anthracycline-resistant ovarian cancer. PATIENTS AND METHODS: Fifty-nine patients who had failed prior platinum- and anthracycline-based chemotherapy were enrolled. During the dose-finding phase, patients received a loading dose of valspodar (1.5 or 2 mg/kg) via 2-hour intravenous (IV) infusion on day 1 and continuous IV infusion (CIVI) of valspodar (2, 4, or 10 mg/kg/d) over 3 days. Doxorubicin (starting from 20 up to 50 mg/m(2)) and cisplatin (50 mg/m(2)) were administered via 15- to 20-minute IV infusions on day 3. During the efficacy phase, patients received at least two treatment cycles unless toxicity was unacceptable, and responding patients and those with stable disease received four to six cycles. RESULTS: All patients completed at least one cycle of combined treatment. The MTD of doxorubicin was determined to be 35 mg/m(2) when administered with valspodar at 2 mg/kg loading dose and 10 mg/kg/d CIVI plus 50 mg/m(2) cisplatin. At these doses, valspodar blood concentrations known to reverse MDR in vitro were reached in all patients. Valspodar was well tolerated at all dose levels. Dose-limiting toxicities of the combination were primarily hematologic and included febrile neutropenia and prolonged leucopenia. The addition of valspodar to the treatment did not worsen cisplatin-related toxicity. Among 33 patients treated at the MTD for doxorubicin, one (3%) had a complete response, and four (12%) had a partial response. An additional seven patients experienced a stabilization of their previously progressive disease. The survival rates at 6 and 12 months were 59% and 19%, respectively. CONCLUSION: Valspodar can be safely coadministered with doxorubicin and cisplatin. Although the regimen used in this trial produced renewed responses in patients with heavily pretreated, refractory ovarian cancer, the value of valspodar in reversing resistance mediated by P-glycoprotein remains to be determined.

Adolescent↗

PubMed2001

Mineralization of 2,4-D, mecoprop, isoproturon and terbuthylazine in a chalk aquifer.

The potential to mineralize 2,4-dichlorophenoxyacetic acid (2,4-D), mecoprop, isoproturon and terbuthylazine was studied in soil and aquifer chalk sampled at an agricultural field near Aalborg, Denmark. Laboratory microcosms were incubated for 258 days under aerobic conditions at 10 degrees C with soil and chalk from 0.15-4.45 m below the surface. The [ring-U-14C]-labeled herbicides were added to obtain a concentration of 6 micrograms kg-1 and mineralization was measured as evolved [14C]carbon dioxide. The herbicides were readily mineralized in soil from the plough layer, except for terbuthylazine, which was mineralized only to a limited extent. In the chalk, lag periods of at least 40 days were observed, and a maximum of 51%, 33% and 6% of the added 2,4-D, mecoprop and isoproturon, respectively, were recovered as [14C]carbon dioxide. Large variations in both rate and extent of mineralization were observed within replicates in chalk. No mineralization of terbuthylazine in chalk was observed. As a measure of the general metabolic activity towards aromatic compounds, [ring-U-14C]-benzoic acid was included. It was readily mineralized at all depths.

2,4-Dichlorophenoxyacetic Acid↗

PubMed2001

Expression of cell cycle proteins in ovarian carcinoma cells in serous effusions-biological and prognostic implications.

OBJECTIVE: The aim of this study was to investigate the expression of cell cycle proteins in ovarian carcinoma cells in serous effusions and respective solid tumors. METHODS: Fifty-five malignant effusions and 38 tumors (20 primary, 18 metastatic) were immunohistochemically stained for cyclin A, p27(kip1), and Ki-67. Staining extent (0-100% cells) and intensity (0-3 scale) were scored. Cyclin A and p27(kip1) expression was additionally studied in 29 malignant effusions using immunoblotting. Immunohistochemistry results in effusions were evaluated for possible association with clinicopathologic parameters. RESULTS: Nuclear immunoreactivity for all markers was detected on carcinoma cells in the majority of effusions using immunohistochemistry. Similarly, immunoblotting showed the presence of cyclin A and p27(kip1) in 29/29 and 25/29 specimens, respectively. Intense (3) immunoreactivity for Ki-67 was detected more often in peritoneal effusions, compared with those of pleural location (P = 0.036). Staining in primary and metastatic lesions was generally comparable to that of tumor cells in effusions. Staining for p27(kip1) was more diffuse in effusion specimens obtained prior to the institution of chemotherapy (P = 0.042). In an analysis of all effusions, an association was observed between the number of cells that were immunoreactive for Ki-67, cyclin A, and p27(kip1) (cyclin A-Ki-67: P = 0.008; p27(kip1)-Ki-67: P = 0.019; cyclin A-p27(kip1): P = 0.032). In survival analysis, the presence of more diffuse (P = 0.042) and intense (P = 0.019) staining for cyclin A correlated with prolonged overall survival. CONCLUSIONS: The expression of the studied cell cycle markers does not differ markedly between ovarian carcinoma cells in the pleural and peritoneal cavity, supporting our previous studies of several metastasis-associated molecules. The presence of cyclin-A-positive cell populations is associated with a more favorable disease outcome, possibly due to the targeting of proliferating cells by chemotherapeutic agents. However, the decline in the fraction of p27(kip1)-positive cells in posttreatment specimens may point to additional mechanisms involved in this selection.

Ascitic Fluid↗

PubMed2001

Mineralization of aged atrazine and mecoprop in soil and aquifer chalk.

The effect of ageing on the bioavailability and sorption of the herbicides atrazine and mecoprop was studied in soil and aquifer chalk sampled at an agricultural field near Aalborg, Denmark. The herbicides were incubated in sterile soil or chalk up to 3 months prior to inoculation with 5 x 10(7) cells g(-1) (dry weight) of a mecoprop degrading highly enriched culture (PM) or 1 x 10(9) cells g(-1) (dry weight) of the atrazine degrading Pseudomonas sp. strain ADP. As a measure of the bioavailable residues accumulated 14CO2 was measured for 2 months. In both soil and chalk ageing limited the rate of atrazine mineralization, and in chalk the extent of mineralization was reduced as well. The fraction of sorbed atrazine in the soil ranged between 50% and 62%, whereas a maximum of 12% was sorbed in chalk. No impact on the mineralization of aged mecoprop was seen as no sorption of this herbicide on either soil or chalk was measured.

2-Methyl-4-chlorophenoxyacetic Acid↗

PubMed2001

Ovarian carcinoma cells in serous effusions show altered MMP-2 and TIMP-2 mRNA levels.

The expression of matrix metalloproteinases (MMP) and their inhibitor TIMP-2 in serous effusions from patients with ovarian carcinoma and its association with clinico-pathological parameters were analysed. The findings in carcinoma cells in effusions were compared with corresponding primary and metastatic lesions. Sixty-six effusions and 96 tissue sections were stained for MMP-1, MMP-2 and MMP-9 applying immunohistochemistry (IHC) and analysed for MMP-2, MMP-9 and TIMP-2 expression using mRNA in situ hybridisation (ISH). MMP-2 and MMP-9 mRNA levels in 30 effusions were subsequently analysed using reverse transcription- polymerase chain reaction (RT-PCR). MMP and TIMP expression was detected in both carcinoma and mesothelial cells in effusions. The levels were consistently higher in malignant cells, significantly so for MMP-1 (P=0.016) and MMP-2 (P=0.036) proteins, as well as for TIMP-2 mRNA (P=0.008). In tissue sections, MMP-1, MMP-2 and MMP-9 protein expression was mostly localised to tumour cells, while MMP-2, MMP-9 and TIMP-2 mRNA were predominantly detected in stromal cells. Adenocarcinoma cells in effusions showed a significant upregulation of MMP-2 expression compared with primary tumours, with a concomitant downregulation of TIMP-2. RT-PCR demonstrated the presence of MMP-2 and MMP-9 in 28/30 and 0/30 specimens, respectively. MMP and TIMP are thus mainly synthesised by cancer cells in effusions, while stromal cells have a similar role in solid tumours. MMP-1 and MMP-2 production predominates over that of MMP-9 in effusions. Increased MMP-2 and reduced TIMP-2 levels are seen in ovarian carcinoma cells in effusions, possibly marking the acquisition of a metastatic phenotype.

Ascitic Fluid↗

PubMed2001

Clear-cell and papillary serous cancer: treatment options.

Clear-cell carcinoma (CCC) and serous papillary carcinoma of the endometrium (UPSC) are rare subtypes of endometrial carcinoma (10%). The histological diagnosis can be made on the dilation and curettage specimens in both types in a very high percentage of the cases. This is important in the planning of treatment. CCC and UPSC are associated with about 50% of all relapses occurring in endometrial carcinoma, and the 5-year survival rate is, on average, 42% and 27% respectively. Surgico-pathological stage, age, and vessel invasion are independent prognostic factors for both groups. The recurrence rate is extremely high, and the most frequent extra-pelvic sites of relapse are the upper abdomen, lungs and liver. Stage Ia patients treated with complete surgical staging alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. The treatment of patients with CCC and UPSC stage Ib, Ic, II and III should include radical debulking surgery and some form of adjuvant therapy, but it is not clear which type is most effective. Adjuvant pelvic radiotherapy plus intracavitary radiotherapy is usually given in early-stage disease and pelvic radio therapy/or whole abdomen irradiation plus adjuvant systemic chemotherapy (PAC) in advanced disease. However, we are urgently waiting for a large prospective randomized study to compare both modalities. Paclitaxel, alone or in combination, is currently being tested in phase II studies.

Adenocarcinoma, Clear Cell↗

PubMed2001

Ets-1 mRNA expression in effusions of serous ovarian carcinoma patients is a marker of poor outcome.

Ets-1 proto-oncogene is a transcription factor with a role in the activation of metastasis-associated molecules. We recently found that Ets-1 mRNA expression in solid tumors is a marker of poor prognosis in ovarian carcinoma. The objective of this study was to compare the expression of Ets-1 mRNA in effusions and primary and metastatic tumors of serous ovarian carcinoma patients and to evaluate its prognostic role in effusions. Sections from 67 malignant effusions and 90 primary and metastatic lesions were evaluated for expression of Ets-1 using mRNA in situ hybridization. Expression of Ets-1 mRNA was detected in carcinoma cells in 24 of 67 (36%) effusions. Expression in cancer cells was similar in peritoneal and pleural effusions. In solid lesions Ets-1 expression was detected in both tumor cells and stromal cells in 34 of 90 (38%) lesions. Ets-1 expression in tumor cells showed a strong association with that of stromal cells (p <0.001). Ets-1 expression in effusions showed an association with mRNA expression of basic fibroblast growth factor, previously studied in this patient cohort (p = 0.019). Ets-1 expression in solid lesions showed an association with mRNA expression of vascular endothelial growth factor (p <0.001 for both carcinoma and stromal cells), basic fibroblast growth factor (p = 0.007 for carcinoma cells, p = 0.006 for stromal cells), and interleukin-8 (IL-8) (p = 0.001 for tumor cells). Ets-1 mRNA showed upregulation in metastases when compared with effusion specimens (p = 0.028). In univariate survival analysis Ets-1 expression in carcinoma cells in effusions correlated with poor survival (p = 0.003). Our findings confirm the role of Ets-1 as a novel prognostic marker in advanced-stage ovarian carcinoma and extend it to effusion specimens. The elevated expression in solid metastases supports a central role in tumor progression as well. The association between Ets-1 mRNA expression and the expression of angiogenic genes, documented also in our previous study, points to the close link between these molecules, in agreement with the role of angiogenic genes in the transcriptional activation of Ets-1. The identical phenotype of carcinoma cells in pleural and peritoneal effusions provides further evidence for our theory that cells at these sites share similar genotypic and phenotypic profiles.

Adult↗

PubMed2001

Fibroblast growth factor receptor 3 (FGFR3) - analyses of the S249C mutation and protein expression in primary cervical carcinomas.

Fibroblast growth factor receptor 3 (FGFR3) seems to play an inhibitory role in bone development, as activating mutations in the gene underlie disorders such as achondroplasia and thanatophoric dysplasia. Findings from multiple myeloma (MM) indicate that FGFR3 also can act as an oncogene, and mutation of codon 249 in the fibroblast growth factor receptor 3 (FGFR3) gene was recently detected in 3/12 primary cervical carcinomas. We have analysed 91 cervical carcinomas for this specific S249C mutation using amplification created restriction site methodology (ACRS), and detected no mutations. Immunohistochemistry was performed on 73 of the tumours. Reduced protein staining was seen in 43 (58.8%) samples. Six of the tumours (8.2%) revealed increased protein staining compared with normal cervical tissue. These patients had a better prognosis than those with reduced or normal levels, although not statistically significant. This report weakens the hypothesis of FGFR3 as an oncogene of importance in cervical carcinomas.

Adult↗

PubMed2001

Expression of membrane-type 1, 2, and 3 matrix metalloproteinases messenger RNA in ovarian carcinoma cells in serous effusions.

We studied the levels of matrix metalloproteinase (MMP)-2, membrane-type (MT)1-MMP, MT2-MMP, and MT3-MMP in 43 malignant pleural and peritoneal effusions using reverse transcription-polymerase chain reaction (RT-PCR) and cellular localization of MT1-MMP in 66 effusion specimens and 85 corresponding primary and metastatic tumors using messenger RNA (mRNA) in situ hybridization (ISH). In 43 effusions, MMP-2 mRNA was detected in 37, MT1-MMP in 25, and MT2-MMP in 32. Expression of MT1-MMP and MT2-MMP was found in 21 specimens; in 16 MT-MMP-positive specimens, mRNA for only 1 of 2 enzymes was expressed. MT3-MMP mRNA was not detected. High levels of MMP-2 mRNA were detected more often in effusions with high MT1-MMP and/or MT2-MMP mRNA expression. Using ISH, MT1-MMP mRNA was localized to cancer cells in 27 of 58 malignant effusions; focal signals were detected in mesothelial cells in 7 of 42. MT1-MMP was localized to tumor cells in 32 of 85 primary and metastatic solid lesions, and stromal cells expressed MT1-MMP in 3. Tumor cell MT1-MMP expression in effusion specimens did not differ from primary or metastatic lesions. MT-MMP expression in tumor cells in effusions showed no association with effusion site or tumor type using ISH and RT-PCR.

Ascitic Fluid↗

PubMed2001

Expression levels of the nerve growth factor receptors TrkA and p75 in effusions and solid tumors of serous ovarian carcinoma patients.

PURPOSE: The purpose of this study was to analyze the expression of the high- and low-affinity nerve growth factor (NGF) receptors TrkA and p75 in effusions and in primary and metastatic tumors of serous ovarian carcinoma patients, as well as to evaluate their association with clinicopathological parameters and disease outcome. EXPERIMENTAL DESIGN: Sections from 77 malignant effusions and 78 primary and metastatic lesions were evaluated for protein expression of TrkA and p75 using immunohistochemistry (IHC). Expression of the phosphorylated form of TrkA (p-TrkA) was evaluated in 75 effusions using IHC. TrkA and p75 mRNA expression was studied in 44 effusions using reverse transcription-PCR (RT-PCR). RESULTS: TrkA protein membrane expression was detected in carcinoma cells in 30 of 77 (39%) effusions and 64 of 78 (82%) solid tumors. The decrease in TrkA expression in effusions approached, but did not reach, statistical significance when only corresponding lesions were analyzed (P = 0.06 in the comparison of effusions and primary tumors, P = 0.09 for effusions and metastases). Conversely, p75 protein membrane expression was more common in effusions, which was detected in 16 of 77 (21%) effusions as compared with 6 of 78 (8%) solid tumors (P > 0.05 in analysis of corresponding lesions). Expression of p-TrkA in carcinoma cells was limited to 5 of 75 effusions. Interestingly, 11 of 16 p75-positive effusions were also immunoreactive for the antibody against TrkA (P = 0.001), suggesting NGF activation using two signaling pathways. TrkA and p75 protein expression in tumor cells was similar in pleural and peritoneal effusions (P > 0.05). Using reverse transcription-PCR, TrkA mRNA was detected in 2 of 45 effusions, whereas p75 mRNA was present in 3 of 45 specimens. TrkA and p75 showed no association with tumor grade, Fédération Internationale des Gynaecologistes et Obstetristes stage, chemotherapy status, the extent of residual disease, or survival (P > 0.05). CONCLUSIONS: TrkA and p75 are both expressed in advanced-stage ovarian carcinoma, but whereas p75 expression is elevated in effusions, TrkA shows an opposite trend. The different expression of NGF receptors in effusions may relate to the different microenvironment and growth factor availability in body cavities, as also supported by the infrequent activation of TrkA in effusions. The similar expression of TrkA and p75 in carcinoma cells in pleural and peritoneal effusions provides further evidence for our hypothesis that there are few, if any, phenotypic differences between ovarian carcinoma cells at these two sites. TrkA and p75 expression in effusions does not appear to be a predictor of disease outcome in advanced-stage serous ovarian carcinoma.

Animals↗

PubMed2000

Expression of apoptosis-related proteins is an independent determinant of patient prognosis in advanced ovarian cancer.

PURPOSE: The present study was undertaken to investigate the prognostic and predictive relevance of the expression of apoptosis-related proteins Bax, Bcl-X(L), and Mcl-1 in advanced ovarian cancer. PATIENTS AND METHODS: Tumor biopsies from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for the expression of Bax, Bcl-X(L) and Mcl-1 proteins. Their prognostic relevance was examined in a uni- and multivariate survival analysis. RESULTS: Sixty-six percent of cancer cases expressed Bax, 62% Bcl-X(L), and 53% Mcl-1. The expression of Bax correlated with tumor differentiation (P: =.016) and less residual disease after surgery (P <.0001). In univariate analysis, Bax expression was associated with improved (P =.0004) prognosis and Mcl-1 expression with poorer (P =.011) prognosis. None of the factors studied was of independent prognostic significance by itself, but when Bax and Bcl-2 expression data were considered together, this combined variable was of independent prognostic significance (P =.0115), together with residual disease status (P =.0016), differentiation grade (P =.0014), and the presence of ascites (P =.0122). Patients with a long median survival (104 months) could be discriminated from those with a short one (16 months) by combining the individual patients' expression data for p53, Bax, and Bcl-2 with their residual disease status (P <.00001). None of the factors studied was able to predict response to chemotherapy. CONCLUSION: The expression of selected apoptosis-related proteins is of independent prognostic significance and may be helpful in a molecular substaging of patients with stage III ovarian cancer.

Adult↗

PubMed2000

Carcinoma of the fallopian tube.

BACKGROUND: The objective of the current study was to increase insight into the biology of fallopian tube carcinoma through an analysis of possible clinical and pathologic determinants of prognosis and to formulate recommendations with regard to a more optimal therapeutic approach for patients with this rare disease. METHODS: A study was performed of the pathology specimens and clinical case records from 151 patients with fallopian tube carcinoma who were treated consecutively. Both univariate and multivariate analyses of possible prognostic factors were performed for the whole group and for the subgroup of 41 patients with Stage I disease. The possible significance of serum CA-125 levels as a tumor marker and a marker of response to platinum-containing chemotherapy was evaluated. RESULTS: In multivariate analysis, disease stage, the presence of residual tumor, and a hydrosalpinx-like appearance of the fallopian tube were of independent prognostic significance for the whole cohort. For patients with Stage I disease, the depth of infiltration in the tubal wall and intraoperative tumor rupture were of independent prognostic significance. The marked tendency of this disease for extraperitoneal spread, even in apparently early stages, was confirmed. In 37 evaluable, platinum-naïve patients, an overall response rate of 70% was obtained with platinum-based chemotherapy, with a median response duration of 12.5 months. In view of its low efficacy and high rate of serious complications, the use of postoperative radiotherapy in the treatment of patients with fallopian tube carcinoma is no longer recommended. Serum CA-125 level measurements in fallopian tube carcinoma patients have the same significance as tumor and surrogate markers of response as in ovarian carcinoma patients. CONCLUSIONS: Prognostic factors in patients with early stage (Stages 0 and I) fallopian tube carcinoma seem to differ from those in patients with early stage ovarian carcinoma. For patients with more advanced stage disease, due to the striking similarities in prognostic and clinical characteristics between the two diseases, the authors recommend that the treatment and follow-up strategies for patients with ovarian carcinoma be adopted in the management of patients with fallopian tube carcinoma.

Adenocarcinoma↗

PubMed2000

Primary cervical carcinomas show 2 common regions of deletion at 3P, 1 within the FHIT gene: evaluation of allelic imbalance at FHIT, RB1 and TP53 in relation to survival.

Chromosome arm 3p is re-arranged in many tumor types, including cervical carcinomas. Putative tumor-suppressor genes on 3p have been proposed, including the FHIT gene, which maps to chromosome band 3p14.2. We have analyzed 79 primary cervical carcinomas for allelic imbalance (AI) at 17 chromosome 3 loci, including 3 within the FHIT gene. Expression of the FHIT gene was evaluated after immunohistochemistry with an antibody against the pFHIT protein. Previously determined human papillomavirus status, defined after in situ hybridization, showed type 16 or 18 in 56/77 tumors. Tumors were also analyzed for AI at loci within the RB1 (chromosome band 13q14.2) and the TP53 (17p13) genes for AI. AI was found at 1 or more 3p loci in 50/79 tumors, at frequencies ranging from 30% to 52% at the individual loci. Two smallest regions of overlapping deletion (SROs) were found, 1 including parts of the FHIT gene (SRO flanked by D3S1481 and D3S1313) and another more distal SRO between D3S32 and D3S1286. FHIT protein expression was reduced in 57/69 (83%) tumors but not associated with AI at FHIT loci (p = 0.56). AI was found in TP53 and RB1 in 18% and 29% of the samples, respectively. Relapse-free survival was associated with AI in the TP53 gene in both a univariate (p = 0.0003) and a multivariate (p = 0.004) analysis. This study confirms a high frequency of AI at chromosome arm 3p in primary cervical carcinomas. The AI results and the reduced FHIT protein staining indicate that FHIT alterations are important in cervical carcinogenesis.

Acid Anhydride Hydrolases↗