Is there any progress in the outcome of patients suffering from ovarian cancer? Treatment strategies since 1957.
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Female↗
Biomedical subjects
A Pfleiderer
Publications and source records attributed to A Pfleiderer.
Randomized study comparing carboplatin/cyclophosphamide and cisplatin/cyclophosphamide as first-line treatment in patients with stage III/IV epithelial ovarian cancer and small volume disease. German Ovarian Cancer Study Group (GOCA).
UNLABELLED: Several randomized studies in patients with advanced ovarian cancer have dealt with the comparison of cisplatin and carboplatin when given as either a single drug or in combination. The German Ovarian Cancer Study Group (GOCA) performed a prospective randomized trial in a subgroup of patients specified by a successful cytoreductive operation before the start of chemotherapy. From February 1987 to May 1990, 173 previously untreated patients with stage III and IV disease and limited tumor bulk of <2 cm postoperatively received either cyclophosphamide 600 mg/m2 plus carboplatin 350 mg/m2 or cyclophosphamide 1000 mg/m2 plus cisplatin 80 mg/m2. The drugs had to be administered on Day 1 every 28 days for six subsequent courses. RESULTS: In 158 assessable patients no significant differences in pathologically confirmed CR rates (pCR: 14% vs 16%), median time to progression (PFI: 19 months vs 26 months), and overall survival (OS: 35 months vs 37 months) were observed. Refusal of therapy due to toxicity was more frequent in the cisplatin arm, whereas patients with progressive disease predominated in the carboplatin arm. Nonhematologic adverse effects were more likely to occur with cisplatin whereas carboplatin patients experienced more myelosuppression. As prognostic factors associated with an increased risk of progressive disease and shorter overall survival time, stage of disease and amount of residual tumor after first surgery were determined. CONCLUSIONS: Carboplatin proved to be effective in patients with optimally debulked ovarian cancer. However, neither regimen used in this trial is sufficiently active to prevent tumor progression in the majority of patients.
Adult↗
Diagnostic formula for the differentiation of adnexal tumors by transvaginal sonography.
OBJECTIVE: To create a strategy for sonographic differentiation of benign and malignant adnexal tumors in premenopausal and postmenopausal patients. METHODS: Multiple sonomorphologic criteria were analyzed prospectively in 754 tumors. Four hundred were found in premenopausal and 354 in postmenopausal women. In a logistic regression model, relevant criteria were selected, and a diagnostic formula for tumor differentiation was derived. RESULTS: There were 165 malignant tumors, of which 37 (9.2%) were found in premenopausal and 128 (36.2%) in postmenopausal women. In both groups, the criteria of solid phase and ascites were the most significant. Further important diagnostic criteria were structure and tumor size in premenopausal women and cyst architecture and tumor surface in postmenopausal women. These results allowed an estimation of the probability of malignancy. Using a cutoff point of 10% for the probability to classify tumors as malignant, the sensitivity and specificity in premenopausal patients were 86.5% and 92.6%, respectively, with an accuracy of 92%. In postmenopausal women, the sensitivity, specificity, and accuracy were 93%, 82.7%, and 86.6%, respectively. Assuming a prevalence as given in the study, the positive and negative predictive values were 54.4% and 98.5% in premenopausal and 75.3% and 95.4% in postmenopausal women. CONCLUSIONS: With four binary criteria, a useful diagnostic formula for tumor differentiation was obtained. However, estimates for sensitivity, specificity, and accuracy may be too optimistic because they were derived from the same data that were already used for model selection.
Adnexa Uteri↗
Increasing incidence of CD44v7/8 epitope expression during uterine cervical carcinogenesis.
Splice variants of the cell surface glycoprotein CD44 (CD44v) have been implicated in the progression of various human tumors. In the present study, we have examined the expression pattern of a CD44v epitope encoded by the adjacent variant exons v7 and v8 during human cervical carcinogenesis. While only l/ll normal cervical squamous epithelia was positive for this epitope by immunohistochemistry, 4/21 samples of low-grade squamous intra-epithelial lesions (LSIL), 17/35 samples of high-grade squamous intra-epithelial lesions (HSIL), 11/12 samples of the HSIL subgroup of carcinomas in situ and 17/17 cases of invasive cervical carcinoma showed CD44v7/8 epitope expression. In addition to CD44 variant expression, we have analyzed 67 lesions for the presence of HPV16/18-DNA using PCR. Most of the samples expressing the v7/8 epitope were also HPV16-positive (29/32), whereas only 17/35 of the v7/8-negative samples were HPV16-positive. HPV18 DNA was found in only one invasive carcinoma. Our data suggests that high-risk HPV infection may precede CD44v7/8 expression and that the number of samples expressing the CD44v7/8 epitope increases during carcinogenesis and reaches nearly 100% at the carcinoma in situ stage. This CD44 epitope could, therefore, serve as a diagnostic marker of cervical squamous cell carcinomas and as a possible target for CD44v7/8 epitope-directed therapies.
Alternative Splicing↗
[Combined evaluation of ovarian tumors with transvaginal B-image and color Doppler ultrasound].
Transvaginal sonomorphologie and colour Doppler measurements were obtained preoperatively in 212 adnexal tumours: 81 premenopausal tumours (13 malignant and 68 benign) and 131 postmenopausal tumours (55 vs 76). Tumours were divided into five different scores according to their sonomorphology [16]. Scores I and II are related to benign tumours. Score V represents typically malignant tumours. Scores III and IV are associated with benign and malignant tumours. If score I and II are considered as benign and score III to V as malignant the sensitivity in pre- and postmenopausal tumours is 90%. However, the specificity is only 56% vs 70% respectively. In order to improve the accuracy, colour Doppler was additionally performed in tumours with sonomorphological score III and IV. The following criteria were tested: minimum resistance index (Rlmin), number of tumour arteries (ART), maximum (Smax) and sum (Ssum) of peak systolic velocities. All criteria showed significant differences between benign and malignant tumours. Tumours of score III and IV were differentiated by colour Doppler with an accuracy between 66% and 81% for premenopausal and 69% to 86% for postmenopausal women. The combination of sonomorphology and colour Doppler increased the accuracy between 84% and 90% with a sensitivity of up to 92% in pre- and 89% in postmenopausal patients. Sequential colour Doppler sonography as a supplement to transvaginal sonography improves tumour differentiation. The limitation of colour Doppler measurements to score III and IV lesions reduced the length of examination time to a reasonable extent.
Adolescent↗
p53 mutation and MDM2 amplification are rare even in human papillomavirus-negative cervical carcinomas.
BACKGROUND: Mutation of the p53 tumor suppressor gene is the most commonly found genetic alteration in human cancer. The E6 gene product of human papillomavirus (HPV) 16 and 18 can inactivate the p53 protein by promoting its degradation. Because most HPV-positive cervical carcinoma cell lines contain wild-type p53 whereas HPV-negative cell lines have point mutations in the p53 gene, a major role in the development of HPV-negative cervical cancer has been attributed to p53. Recent studies, however, have observed no consistent presence of p53 mutation in HPV-negative primary cervical carcinomas. The MDM2 oncogene, which forms an autoregulatory loop with the wild-type p53 protein, has been found amplified in a high percentage of human sarcomas, thus abolishing the antiproliferative function of p53. METHODS: Forty-three primary cervical carcinomas and 10 autopsy-derived distant metastases from one patient were examined for p53 mutation and MDM2 amplification. These tumors had been selected from 238 cervical cancers that had been HPV-typed by Southern blot hybridization and polymerase chain reaction as a representative sample for their HPV status and their clinicopathologic characteristics. Seventeen of the cases had a remarkably good or poor clinical outcome. Human papillomavirus DNA sequences had been detected in 30 of these 43 primary tumors and 13 were negative for HPV by both methods. p53 mutation in the highly conserved exons 5-8 was studied by single-strand conformation polymorphism analysis and direct sequencing. MDM2 amplification was analyzed by Southern blot hybridization. RESULTS: Only two missense point mutations and one nucleotide sequence polymorphism were detected: a TAC-->TGC transition in codon 234 in exon 7, resulting in a Tyr-->Lys substitution, a CGT-->TGT transition in codon 273 in exon 8, resulting in an Arg-->Cys substitution and a polymorphism (CGA-->CGG) in codon 213 in exon 6. Both tumors revealing the point mutations were HPV-negative carcinomas. Amplification of the MDM2 gene was observed in 1 of the 53 specimens tested. CONCLUSIONS: In contrast to data derived from cultured cervical carcinoma cell lines and primary sarcomas, these results indicate that p53 mutation and amplification of the MDM2 oncogene are rare even in HPV-negative primary cervical carcinomas. However, to the authors; knowledge, this is the first observation of MDM2 amplification in humans outside sarcomas and neuroepithelial tumors.
Adult↗
Prognostic value of DNA ploidy and S-phase fraction in stage I endometrial carcinoma.
Both nuclear DNA content and S-phase fraction (SPF) can be helpful in predicting prognosis in certain malignancies. We investigated in a retrospective study the prognostic significance of nuclear DNA content and SPF as measured by flow cytometry of tumor specimens from 162 women with nonpretreated surgically staged FIGO stage I endometrial cancer using clearly defined inclusion criteria. A total of 139 (86%) cases were found to be diploid, whereas 23 (14%) were aneuploid. Ploidy showed a correlation with histologic grade, estrogen as well as progesterone receptor levels, and depth of myometrial infiltration. Univariate analysis of follow-up data showed an increased relative risk (RR) for recurrence-free survival (RFS) for grade 3 tumors (RR = 2.11, ns), for age (RR = 1.04, P = 0.023) as a continuous variable, and for SPF in diploid tumors (RR = 3.10, P = 0.035). In addition, univariate analysis of overall survival revealed similar results with a slightly increased relative risk for ploidy (RR = 1.52, ns). Multivariate analysis of RFS showed age as the only independent prognostic factor. Multivariate analysis of RFS for diploid tumors showed no independently significant factor; however, age as a continuous variable with a relative risk of 1.04 and SPF with a relative risk of 2.94 were of borderline significance. Our results suggest that abnormalities of the nuclear DNA content and SPF in this homogeneous group of patients are associated with clinical and morphological prognosticators; however, ploidy is no independent prognostic factor for RFS. For diploid tumors, SPF might be a possible independent prognostic factor.
Aged↗
[Surgical oncology and quality of life].
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Activities of Daily Living↗
Microsatellite instability in ovarian neoplasms.
Microsatellite instability has been observed in a variety of sporadic malignancies, but its existence in sporadic ovarian cancer has been the subject of conflicting reports. We have performed a polymerase chain reaction-based microsatellite analysis of DNAs extracted from the neoplastic and non-neoplastic tissues of 41 ovarian cancer patients. Tumour-associated alterations were observed in seven (17%) of these cases. Clinicopathological correlations revealed that: (1) alterations among tumours classified as serous adenocarcinomas occurred with relatively low frequency (2/24 or 8%); (2) most of the tumours with microsatellite alterations (5/7 or 71%) were of less common histopathological types (epithelial subtypes such as endometrioid and mixed serous and mucinous, or non-epithelial types such as malignant mixed Müllerian or germ cell tumours); (3) tumour-associated alterations were observed in 3/4 (75%) of the patients with stage I tumours vs 4/37 (11%) of the patients with stage II, III and IV tumours (P = 0.01); (4) tumour-associated microsatellite instability was found to occur with similar frequencies among patients with and without clinical features suggestive of familial disease, including positive family history, early onset, or multiple primary tumours. In summary, we have observed microsatellite alterations in the neoplastic tissues of ovarian cancer patients with diverse genetic backgrounds and clinicopathological features. The pattern of alterations is consistent with the possibility that multiple mechanisms may be responsible for microsatellite instability in ovarian neoplasms.
Adult↗
Differential diagnosis of breast lesions by color Doppler.
Color Doppler allows flow detection in small tumor vessels. Due to the vascularity associated with the growth of malignancies, this method can be used to differentiate between benign and malignant breast lesions. In order to study the typical flow characteristics, we investigated multiple Doppler flow parameters. A UM9 HDI (ATL) was used with a linear transducer L 10-5. The number of tumor vessels and the mean, maximum and total flow velocity were measured in 325 benign and 133 malignant lesions and showed highly significant differences (p < 0.0001). Flow profiles (resistance index and systolic/diastolic frequency ratio) showed a large overlap and did not allow accurate tumor differentiation when mean and minimum values were analyzed. Surprisingly, the maximum resistance index and systolic/diastolic frequency ratio were significantly higher in carcinomas than in benign lesions, but the overlap of the values was wider than the flow velocity measurements. Using the vessel number and the total tumor vascularity, 90% of all lesions could be differentiated. A difficulty that we encountered was that a few cancers have very low flow values and some of the proliferative benign lesions can have increased flow.
Adolescent↗
Recurrent cytogenetic aberrations in human ovarian carcinomas.
Successful cytogenetic analysis was performed on short-term cultures of 62 malignant ovarian tumors from 42 patients. Twenty-three tumors from 18 patients revealed clonal chromosome abnormalities. Five cases showed nonclonal chromosome changes. In the remaining 19 cases, a normal female karyotype was found. Numerical or single structural changes were found in only 11 carcinomas from nine patients. Trisomy 12 and 7 were each the sole abnormality in two cases a piece. One tumor showed a trisomy 6 as the only karyotypic change. Four tumors revealed simple translocations and deletions affecting the chromosomes X, 1, 2, 6, and 7. Twelve of the cytogenetically abnormal tumor samples showed complex karyotypes with both numerical and structural aberrations leading to hyperdiploid, near-triploid, and near-tetraploid stemlines. The recurrent numerical imbalances were losses of the chromosomes 1 (N = 5), X (N = 3), and 17 (N = 3), and gains of the chromosomes 12 (N = 5) and 20 (N = 3). Regarding structural rearrangements, the chromosome bands 11p13-14 and 19p13 were the most frequently affected regions. 11p13-14 was rearranged in four tumors. In two cases, a deletion 11p13-14 was found. Two tumors revealed a nonreciprocal translocation involving 11p13-14 and leading to the loss of distal 11p material. The most consistent finding was a 19p+ marker chromosome, which was present in five different ovarian carcinomas. Our results are in accordance with a recent cytogenetic report describing a 19p+ marker and loss of 11p material as consistent cytogenetic aberrations in human ovarian carcinomas.
Adenocarcinoma↗
DNA flow cytometry in node-positive breast cancer. Prognostic value and correlation with morphologic and clinical factors.
OBJECTIVE: To help clarify the possible usefulness of nuclear DNA content and S-phase fraction (SPF) as additional prognostic factors in node-positive breast cancer patients because there is increased interest in the development of new factors that might provide more detailed prognostic information. STUDY DESIGN: We performed a DNA and SPF analysis by flow cytometry using a multivariate statistical model on a group of 139 node-positive breast cancer patients with clearly defined inclusion and exclusion criteria. RESULTS: The percentage of aneuploidy increased with the number of involved nodes. Aneuploid tumors were more often found among grade 3 and among receptor-negative tumors. Univariate analysis showed a strong effect on recurrence-free survival (RFS) for the number of involved nodes (P < .001) and for tumor size (P = .013). Grade 3 and receptor-negative tumors showed a nonsignificant trend toward increased risk. The relative risk of aneuploid tumors was 1.19 (95% confidence interval, 0.75-1.87). Multivariate analysis revealed only the number of involved nodes to be an independent prognostic factor (P = .002); ploidy showed no effect (P = .684). SPF did not show any significant effect on RFS, even in a univariate analysis. CONCLUSION: These results suggest that nuclear DNA content and SPF correlate with morphologic factors. Their routine clinical use, however, in node-positive breast cancer patients receiving adjuvant therapy seems to have no clinical relevance and therefore can be omitted.
Aneuploidy↗
Cellular DNA content and survival in advanced ovarian carcinoma.
BACKGROUND: The prognosis of patients with advanced ovarian cancer is generally poor. To date, no satisfactory methods for predicting individual prognosis have been reported, especially in patients with little or no residual tumor after debulking. METHODS: The authors investigated in a retrospective study the prognostic significance of nuclear DNA content as measured by flow cytometry of the tumor specimens from 184 women with nonpretreated International Federation of Gynecology and Obstetrics Stage III and IV ovarian cancer. Clearly defined inclusion criteria for the study population were used. RESULTS: Seventy-one (39%) cancers were diploid, whereas 113 (61%) were aneuploid. Ploidy showed a significant correlation with clinical and morphologic features such as age, histologic grade, serous histologic type, and residual tumor after debulking. No significant correlation was found between ploidy and ascites, estrogen- and progesterone receptor levels, and elevated pretreatment CA-125 levels. Univariate analysis showed significant correlations between overall survival and histologic grade (P = 0.003), patient age (P = 0.001), residual tumor after primary surgery (P < 0.001), stage (P = 0.019) and ploidy (P = 0.009). Multivariate analysis revealed residual tumor (P < 0.001) and age (P = 0.051) to be associated independently with survival. Ploidy was not established as an independent prognostic factor. CONCLUSIONS: These results suggest that abnormalities of the nuclear DNA content in advanced ovarian carcinomas are associated with various clinical and morphologic prognosticators, but that ploidy is not an independent prognostic factor for survival.
Adult↗
Human papillomavirus DNA in cervical carcinoma--correlation with clinical data and influence on prognosis.
Human papillomavirus (HPV) is a main factor in cervical carcinogenesis. However, data on the correlation of HPV with clinical features and the prognosis of cervical carcinoma remain controversial. The HPV status (positivity, type, copy number) in unfixed tissue specimens of 205 primary invasive cervical carcinomas was determined by Southern blot hybridization. A correlation with comprehensive clinical and histopathologic data and long-time survival was evaluated. HPV DNA was detected in 73% of the cases; 83% of the HPV-positive tumors contained HPV 16. HPV 16 was predominant among squamous-cell carcinomas (SCC) (p = 0.05). HPV 16 copy number was higher in keratinizing tumors (p < 0.05), and elevated levels of the SCC antigen were more common in patients positive for HPV 16 (p < 0.03). No association was found between the HPV status and 8 other clinical and histopathologic variables. Multivariate analysis after a median follow-up of 73 months demonstrated longer survival for patients with lower clinical stage (p = 0.001) and keratinizing SCC (p = 0.005). Women with HPV-negative tumors had a higher risk of death (RR 1.51; p = 0.07). HPV analysis does not clearly define biologically distinct sub-sets of cervical carcinoma. This underlines the importance of additional factors in cervical carcinogenesis.
Adenocarcinoma↗
Quantitative flow measurements for classification of ovarian tumors by transvaginal color Doppler sonography in postmenopausal patients.
Color Doppler and Duplex measurements were obtained in 83 (42 benign, 41 malignant) ovarian tumors in postmenopausal patients. An ATL UM9/HDI was used. The following flow criteria were analyzed: lowest resistance index (RI) and pulsatility index (PI), total number of arteries and number of central arteries and the maximum, mean and sum of systolic, end-diastolic and time-averaged maximum velocities of all intratumoral vessels. In 98% of malignant and in 85% of benign lesions, vessels were detected. All flow criteria showed highly significant differences between benign and malignant tumors (p < 0.0001). However, there was a considerable overlap between benign and malignant tumors (e.g. the median of the lowest RI was 0.62 (range 0.26-1.0) for benign and 0.40 (0.22-0.66) for malignant tumors; the median of the maximum systolic velocity was 17.5 cm/s (range 5.2-61.5 cm/s) for benign and 47.05 cm/s (14.6-105.0 cm/s) for malignant tumors). Differentiation of malignant tumors by the lowest RI and PI, number of arteries and maximum of systolic flow velocities gave a sensitivity of 77-85%, specificity of 77-83% and accuracy of 80-84%. Differentiation was superior by calculation of the maximum end-diastolic velocities and by the summation of the systolic, end-diastolic and time-averaged maximum flow velocities: sensitivity 90-9.5% specificity 83-86% and accuracy 87-91%. This study confirms that a single measurement is not sufficient for an accurate differentiation of ovarian lesions and, besides the measurement of minimum RI and PI, the measurements of flow velocities as Doppler criteria play an important role.
Journal Article↗
Co-expression of M-CSF transcripts and protein, FMS (M-CSF receptor) transcripts and protein, and steroid receptor content in adenocarcinomas of the ovary.
The co-expression of M-CSF (CSF-1) and its receptor in specimens of ovarian cancer has recently been reported. Preliminary results have already suggested a possible influence of steroids on FMS (M-CSF receptor) expression. Fifty-five non-pretreated FIGO stage III/IV ovarian adenocarcinomas were studied for M-CSF transcripts and protein, as well as FMS transcripts and protein, using standard molecular biological techniques (Northern blot, slot blot analysis) and immunocytochemistry (ICC). Steroid receptor content was measured by DCC analysis in 44/55 specimens; in addition, ER/PR (oestrogen/progesterone) ICC was performed in 32/55 specimens. All tumours were shown to contain M-CSF-specific mRNA. Likewise, M-CSF protein was detected by ICC in the stroma and over the epithelium in all specimens. However, while most tumours were shown to contain FMS-specific mRNA, only 64 per cent of cases showed significant expression of FMS protein by tumour epithelium as shown by ICC. A statistically significant positive correlation was found between M-CSF and FMS mRNA expression levels. A week non-significant positive correlation was noted between FMS mRNA expression levels and tumour grade. Carcinomas were ER-positive in 66 per cent (DCC) or 34 per cent (ICC), and PR-positive in 73 per cent (DCC) or 34 per cent (ICC). A statistically significant positive correlation between ER (DCC) and M-CSF mRNA expression levels was found. Weak non-significant correlations were present between ER (ICC) and FMS (ICC), as well as between PR (DCC) and FMS mRNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenocarcinoma↗
Human papillomavirus DNA in locally recurrent cervical cancer.
Ten vaginal and central recurrences of cervical carcinoma were analyzed by Southern blot hybridization under nonstringent and stringent conditions for the presence of human papillomavirus (HPV) type 11, 16, 18, 31, and 35 DNA. Cases judged HPV-negative by this assay were tested with the polymerase chain reaction (PCR) for HPV 16 and 18. All 10 recurrences were HPV-positive. Seven tumors contained HPV 16, one contained HPV 18, one contained HPV 16 and 18, and one contained HPV-related sequences. In three cases, where the corresponding primary tumor could be studied, the identical HPV type was contained. The consistent presence of HPV DNA in local recurrences of invasive cervical carcinoma argues in favor of a role of these viruses also in the maintenance and reappearance of malignancy.
Aged↗
HPV DNA in autopsy-derived material from multiple metastases of a cervical carcinoma.
Fresh tissue from primary tumor and a metastasis of a cervical carcinoma and 13 autopsy-derived tissue specimens of the same patient were analyzed for HPV DNA by Southern blot hybridization and PCR. Primary tumor and 7 of 10 histologically proven distant metastases contained HPV 16 DNA by Southern blot. PCR detected HPV 16 in all 10 metastases and in 2 of 3 additional tumor-free autopsy-derived tissues. The restriction pattern was identical in all HPV-positive lesions and only slight variations in copy number occurred. Two-dimensional gel electrophoresis showed the viral DNA fully integrated in the cellular genome without any difference between primary tumor and metastasis. The relevance of HPV also for the metastatic spread of the malignant disease is indicated by its conserved presence in multiple distant metastases of cervical carcinoma.
Adult↗