Epithelial Ovarian Malignancies Research Articles

Ovarian cancer and venous thromboembolic risk

Objective. To determine the incidence and the prognostic factors of objectively diagnosed deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with epithelial ovarian malignancy. Methods. We reviewed the records of all patients with epithelial ovarian cancer who were diagnosed, treated, and followed-up at our institution between 1990 and 2001. Data were collected regarding age, body mass index, previous DVT and PE, menopause status, FIGO stage, grade, histology, type of surgery, residual disease, first line chemotherapy, and relapse status. Results. Of the 253 cases, the overall incidence of symptomatic venous thromboembolic events (VTE) was 16.6% (42 patients): 1.6% (4) with PE and 15% (38) with DVT. 8 events (3.2%) were detected before tumor diagnosis, 6 (2.4%) in the postoperative period, 16 (6.4%) during first line chemotherapy and 12 (4.8%) throughout the follow-up period. Risk factors associated with occurrence of VTE were: at diagnosis, history of deep vein thrombosis ( P = 0.001); during chemotherapy, older age ( P = 0.017), larger body mass index ( P = 0.019), FIGO stage 2c–4 ( P = 0.004), no surgery ( P = 0.003), and presence of residual tumor ( P = 0.026). None of the considered risk factors were found to be predictors of VTE postoperatively. The multivariate regression analysis found that residual tumor, age, and body mass index were independent prognostic factors. Conclusion. The incidence of VTE throughout the entire history of ovarian malignancy is high. Prognostic factors could be used to establish prophylaxis protocols based on risk stratification.

Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia

Objective. Increased glucose consumption is a characteristic of malignant cells. Glucose is transported into the cell via facilitative glucose transporters, which are known to be members of a supergene family. The insulin-responsive GLUT4 isoform is expressed almost exclusively in insulin target tissues. P-LAP is a cell surface aminopeptidase, and is a synonym for oxytocinase. P-LAP is also referred to as insulin-regulated membrane aminopeptidase (IRAP) associated with GLUT4-containing vesicle. The authors evaluated P-LAP and GLUT4 expression in benign, borderline, and malignant ovarian epithelia. Methods. Histologic sections of formalin-fixed, paraffin-embedded specimens from 11 patients with benign serous or mucinous cystadenomas, 14 patients with serous or mucinous borderline tumors, and 80 patients with epithelial-ovarian adenocarcinomas (29 serous, 17 endometrioid, 14 mucinous, and 20 clear cell adenocarcinomas) were stained for P-LAP and GLUT4 using each polyclonal antibody. Expressions of P-LAP and GLUT-4 in ovarian cancer cells were detected by Western blotting. Results. P-LAP immunoreactivity was detected in 2 of 11 benign cystadenomas. None of the 11 benign ovarian tumors showed any immunoreactivity for GLUT4. Seven of 14 borderline tumors demonstrated P-LAP immunoreactivity, while 5 of 14 borderline tumors demonstrated GLUT4 immunoreactivity. P-LAP was expressed in 23 of 29 in serous, 15 of 17 endometrioid, 13 of 14 mucinous, and all clear-cell adenocarcinomas. The tendency toward increased P-LAP expression with advancing grade was observed in serous adenocarcinomas. GLUT4 was expressed in 13 of 29 serous, 13 of 17 endometrioid, 13 of 14 mucinous, and 18 of 20 clear-cell adenocarcinomas. In invasive carcinomas, there was a direct correlation between P-LAP immunoreactivity and GLUT4 immunoreactivity (correlation coefficient [ r] = 0.58; P < 0.01). Furthermore, P-LAP overexpression in SKOV3 cells induced the GLUT4 expression. Conclusions. P-LAP and GLUT4 are available not only for the evaluation of ovarian epithelial malignancy, but also as targets for molecular therapy. Further study to investigate the roles of P-LAP and GLUT4 in ovarian carcinoma is needed.

Clinical and biological characteristics of clear cell carcinomas of the ovary in FIGO stages I-II

Clear cell carcinoma of the ovary is considered to be a specific subtype among the epithelial ovarian malignancies. To characterize clear cell carcinomas in early FIGO stages (I-II) with regard to clinical and biological properties, a retrospective study was performed to compare these tumors with other histological subtypes. From a complete series of 226 patients with epithelial ovarian carcinomas in FIGO stages I-II, 28 patients with clear cell carcinomas were selected and the clinical and biological characteristics of these tumors were compared with the remaining non-clear cell carcinomas. All patients underwent primary staging laparotomy followed by adjuvant radiotherapy or chemotherapy. The apoptosis regulators p53, bcl-2 and bax, and the growth factor receptors EGFR and HER-2/neu were analyzed by immunohistochemical techniques and DNA analysis was performed by flow cytometry. Clear cell carcinomas stained negative for p53 significantly more often than other histological subtypes. Positive EGFR staining was seen more frequently in serous carcinomas than in the clear cell carcinomas. Aneuploid DNA status was seen more frequently in clear cell carcinomas than in other histological subtypes and tetraploid tumors made up 50% of the non-diploid tumors. Clear cell tumors were frequently (64%) found in FIGO stages IC and IIC and this was more common than for non-clear cell tumors. No difference was found in the rate of tumor recurrences or survival for patients with clear cell and non-clear cell carcinomas. Clear cell carcinomas of the ovary should be regarded as a separate entity among the epithelial ovarian carcinomas and they differ with regard to both clinical and biological characteristics when compared with non-clear cell tumors.

Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies

Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies

Breast carcinoma cell lysate-pulsed dendritic cells cross-prime MUC1-specific CD8 + T cells identified by peptide-MHC-class-I tetramers

For cancer immunotherapy the loading of dendritic cells (DCs) with whole tumor cell lysate preparations represents a simple and promising approach for presentation of tumor-associated antigens (TAAs), avoiding the disadvantages of HLA-matching and definition of TAAs. The aim of this study was to investigate whether lysate-pulsed DCs efficiently cross-prime CD8 + T cells and induce a strong T H1 cell response, as compared to DCs pulsed with specific peptides (FLU M1 and Melan-A/Mart-1). As a model system breast carcinoma cell lysate from either MCF-7 or MDA-MB-231 cell lines (both HLA-A*0201 +) expressing the TAA MUC1 were selected. Both cell lines expressed MUC1, the epithelial mucin, which is a large molecular weight O-glycosylated protein expressed in the majority of breast, ovarian, and other epithelial malignancies and is under evaluation as a target antigen in cancer immunotherapy. We developed a simple lysate preparation method to solubilize all cell proteins without degradation. For loading of monocyte-derived dendritic cells, 100 μg mL −1 of breast carcinoma cell lysate was used, accompanied by an adjuvant consisting of tumor necrosis factor-α (TNF-α) and prostaglandin-E 2. T cells were co-cultivated with lysate or peptide pulsed DCs and were restimulated weekly. Before cultivation, and after the 3rd stimulation, tetramer frequencies for the MUC1 epitopes M1.2 and F7 as well as for the FLU M1 and Melan-A/Mart-1 epitopes were determined. After stimulation with lysate, higher frequencies for M1.2-specific T cells were observed compared with the F7 epitope. Furthermore, we found expansion factors for M1.2-specific T cells that had been stimulated with MCF-7 lysate-pulsed DCs of up to 43-fold. The analysis of typical T H1/T H2 cytokines (IFN-γ, TNF-α, IL-12p70, IL-2, IL-4, IL-5, and IL-10) revealed a strong T H1 response. These results provide evidence for a strong T H1 polarization and cross-priming of MUC1-specific CD8 + T cells and demonstrate the feasibility of using lysate-pulsed dendritic cells in breast cancer immunotherapy.

Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies.

Ovarian cancer is the leading cause of mortality related to gynecologic malignancies in Sweden but there is no current screening program. Based upon epidemiological research there is evidence that certain reproductive factors are associated with ovarian cancer risk. Most studies generally indicate that each childbirth incurs a 15-20% risk reduction. Women who have used oral contraceptives for 5 years or longer experience about half the risk of ovarian cancer compared with never users. Breastfeeding seems to be protective while age at menarche and at menopause are less consistent risk predictors. Tubal ligation and hysterectomy seem to reduce ovarian cancer risk by up to 80%. Although some studies found endometriosis, polycystic ovarian syndrome (PCOS) and pelvic inflammatory disease (PID) to be positively related to ovarian cancer, the role of these factors is not yet established. Most recent studies observed an approximately 50% ovarian cancer risk increase among ever users of hormone replacement therapy (HRT) compared with never users, and the risk increased further with long-term use. There is less information concerning separate estrogen and progestin effects of HRT and ovarian cancer risk. Although the cause of ovarian cancer remains obscure, hypotheses relating to "incessant" ovulation, excessive gonadotropin secretion, retrograde carcinogen transportation, apoptosis and estrogen/progestin imbalance have been invoked as etiological explanations. All these hypotheses find various epidemiological support. The aim of this review is to summarize the epidemiological findings on reproductive factors and ovarian cancer risk. These findings are considered in the context of etiologic hypotheses and some new research areas are suggested.

Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies

Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies

576 Phase I dose-finding study of the combination of alimta (pemetrexed) and paclitaxel in patients with solid tumors

Objective.Irinotecan (CPT-11) is a DNA topoisomerase I inhibitor which has shown activityin vitroagainst several cancer cell lines and some promising clinical responses in phase I and II trials in various solid tumors. The cytotoxicity of CPT-11 on human ovarian epithelial malignancies was testedin vitroutilizing the ATP chemosensitivity assay. Flow cytometry was also performed on the fresh carcinoma specimens.Methods.Fresh tumor samples were obtained at laparotomy from 20 patients with primary adenocarcinoma of the ovary and 1 patient with heavily pretreated recurrent ovarian carcinoma. Tumors were plated in anin vitrosystem and treated with varying doses of both CPT-11 and its active metabolite SN-38 (7-ethyl-10-hydroxycamptothecin), in addition to a panel of standard chemotherapeutic agents used in treating ovarian cancer. On the sixth day after incubation, ATP levels in remaining cells were measured using a luminometer as an indication of the amount of cell kill compared to untreated controls.Results.Twelve of the 21 tumors were evaluable for a response to CPT-11. Of the 12 tumors tested, 7 were found to have median effect doses of CPT-11 significantly under the clinically achievable peak plasma concentration (range 1.00 × 10−4to 44.67 μM) and 11 of the 12 tumors showed sensitivity to the active metabolite SN38 with median effect doses ranging from 2.00 × 10−4to 0.147 μM. Some of these tumors showed resistance to the standard agents, such as platinum, based on our assay. The heavily pretreated recurrent tumor tested was very sensitive to both CPT-11 and SN38 by our assay. The results of flow cytometry showed that the tumors were composed of heterogeneous populations of cells with mean S phase fractions varying from 7.0 to 17.3%. The only tumor not sensitive to SN38 showed the highest mean S phase activity of 17.3%.Conclusions.Overall, these results suggest that CPT-11 deserves further investigation as a clinically useful chemotherapeutic agent for ovarian cancer.

Management of port-site metastasis after laparoscopic surgery for ovarian cancer

Objective: The purpose of this study was to define the clinical features and long-term prognosis of port-site metastasis after primary laparoscopic surgery for ovarian cancer. Study Design: All the patients with epithelial ovarian cancer or borderline malignancy who had undergone primary laparoscopic surgery at our institution were reviewed. The clinicopathologic parameters, flow cytometric parameters, p53, p27, bax, HER-2/neu, and bcl-2 by immunostaining, presentation of port-site implants, management of the individual patient, and long-term outcome were analyzed. CANCERLINE and MEDLINE (1960-2002) were searched for related papers. Results: Between 1993 and 2001, of the 31 patients with epithelial ovarian cancer or borderline malignancy who underwent primary laparoscopic surgery at Chang Gung Memorial Hospital, 6 (19.4%) had port-site metastasis. The other 2 patients were referred after port-site metastasis. Tumors with port-site recurrences had higher S-fraction than those without (median: 18.2% vs 9.9%, P =.003; relative risk ratio: >15.5% vs ≤15.5% = 38.33; 95% CI, 3.3-449.2). Those patients who have port-site metastasis develop during chemotherapy (n = 2) or after adequate chemotherapy had been given (n = 2) all died of cancer. Two patients have been currently alive without disease, the tumors of whom were p27-positive and p53-, HER-2/neu -, bcl-2-negative. Conclusion: Port-site metastasis after laparoscopic surgery, during chemotherapy or when adequate chemotherapy has been given, is usually associated with poor outcome. Further investigations are necessary to define the mechanisms and effective management to prevent and treat this serious complication. (Am J Obstet Gynecol 2003;189:16-21.)

P53 codon 72 polymorphism and BRCA 1 and 2 mutations in ovarian epithelial malignancies in black South Africans

Mutations in the BRCA and p53 tumor suppressor genes are implicated in the oncogenesis of ovarian tumors although their exact roles remain unclear. Despite recognized ethnic differences in the frequency of ovarian cancer and in genetic polymorphisms between populations, studies carried out so far have focused almost entirely on Caucasian subjects. In this study, undertaken at King Edward VIII Hospital, Durban, South Africa, we examined blood and/or primary epithelial ovarian tumor tissue from 75 black South African women for the presence of the three most commonly occurring BRCA 1 and 2 mutations (185delAG, 5382insC and 6174delT). The p53 codon 72 allele status was also examined and results were compared to a reference cohort comprising 340 ethnically matched subjects. None of the BRCA 1 or 2 mutations were detected in the patient group. The codon 72 Arg allele frequency in lymphocytic DNA was not significantly different compared with the control group. In contrast, in ovarian tumor DNA, the Arg allele was found significantly more frequently than in the controls; this was observed in terms of both Arg allele frequency (45% vs. 31%; P = 0.017) and Arg homozygosity (20% vs. 9%; P = 0.039). Tumors with the more aggressive serous papillary cystadenomatous histology had a markedly higher Arg frequency (45%) than the mucinous cystadenomas (25%). The higher frequency of the Arg allele detected in this study in black South Africans with ovarian tumors suggests a possible role in malignant transformation and may constitute a risk factor for ovarian and other epithelial cancers through mechanisms yet to be elucidated.

Immunohistochemical staining of GLUT1 in benign, borderline, and malignant ovarian epithelia

Aberrant expression of the facilitative glucose transporter GLUT1 is found in a wide spectrum of epithelial malignancies. The authors describe an immunohistochemical study of GLUT1 expression in benign, borderline, and malignant ovarian epithelia. One hundred forty one formalin-fixed, paraffin-embedded sections were immunostained with rabbit anti-GLUT1 using the streptavidin-biotin method. The samples were as follows: 3 endometriotic cysts, 9 serous cystadenomas, 15 mucinous cystadenomas, 17 noninvasive borderline implants, 3 invasive borderline implants, and 3 endosalpingiosis. In addition, 35 borderline tumors (26 serous, 7 mucinous, 2 seromucinous) and 56 adenocarcinomas (50 serous, 4 endometrioid, 2 mucinous) were stained. Benign serous and mucinous cystadenomas and endosalpingiosis were non-staining with GLUT1 antiserum. Twenty-eight of 35 borderline tumors (80%) stained positively, with weak to moderate (1-2+ out of 3) staining intensity and focal or patchy distribution. Seventeen noninvasive serous borderline implants were negatively stained; however, three invasive serous borderline implants were positively stained with GLUT1 antiserum. Fifty four of 56 ovarian carcinomas (96%) stained positively, with moderate to strong (2-3+ out of 3) intensity and multifocal distribution. GLUT1 is a consistent marker of ovarian epithelial malignancy. GLUT1 staining is absent in benign ovarian epithelial tumors, and shows progressively more staining in invasive tumors as compared to borderline tumors. Anti-GLUT1 antibody may be useful in distinguishing invasive from noninvasive serous borderline implants.

The Efficacy of CA-125 and Tissue polypeptide specific antigen in Epithelial Ovarian Malignancy

Purpose : The purpose of this study is to examine the efficacy of CA-125 and tissue polypetide specific antigen(TPS) in patients with epithelial ovarian malignancy by comparing the two tumor markers in accordance with their measurement value at each stage of the disease, histological characteristics and changes in the measurement value before and after surgery.,ind during the period of chemotherapy. Method : We surveyed 22 patients with epithelial ovarian malignancy who were treated at Dong-A Univ. Medical Center between February 2001 and May 2002. Those patients were measured in terms of CA-125 and TPS before and after surgery. Out of them, especially, 11 patients under remission and 8 patients under progression received the blood sampling before and after chemotherapy and their blood samples were analyzed using immunoradiometric assay. Result : There were no significant differences in concentration of CA-125 and TPS according to the disease stages I, II and III(p=0.587). Sensitivity of CA-125 and TPS were measured 77.2% and 86.3%, respectively. The simultaneous use of TPS and CA-125 resulted in increased sensitivity, or 95.4%. From a histologicial view of epithelial ovarian malignancy, TPS was most sensitive to mutinous tumor and CA-125, serous tumor. TPS was significantly decreased from 190.2164.1 U/I before surgery to 79.758.0 U/i after surgery(p=0.034). Similarly, CA-125 was significantly decreased from 292.2396.7 U/ml before surgery to 119.7188.9 U/ml after surgery(p=0.034). In relation, it was stated that such decrease was more significant in TPS than in CA-125. During the 6 course of chemotherapy, 11 patients under the remission of epithelial ovarian malignancy showed significant decreases in concentration of TPS and CA-125 over time(TPS; p=0.032, CA-125;p=0.022). Another 8 patients under the progression of the disease showed significant increases in the two tumor markers(TPS;p=0.029, CA-125;p=0.042). For the former 11 patients, TPS lowered at a pace faster by 2 months than CA-125. Out of the latter, all showed increases in TPS more than normal and 6 patients in CA-125. Conclusion : There were no significant changes in concentration of CA-125 and TPS according to the stages of epithelial ovarian malignancy. The simultaneous use of the two tumor markers led to the increased sensitivity of diagnosis of the disease. TPS was most sensitive to mucinous tumor and CA-125, serous tumor. After surgery, TPS decreased significantly more than CA-125. Under chemotherapy, the progress of the disease was better reflected by TPS than by CA-125. Consequently, TPS is more effective in determining the course of epithelial ovarian malignancy than CA-125.

Expression of 5alpha-reductases in human epithelial ovarian cancer: its correlation with androgen receptor status.

Androgen metabolism and possible actions are considered to play some roles in human epithelial ovarian neoplasms, but the details have not been well studied. We have examined the expression of 5α‐reductase type 1 and type 2, which catalyze the conversion of testosterone to more active androgen, 5α‐dehydrotestosterone, and androgen receptor (AR), using immunohistochemistry (104 cases) and reverse transcription‐polymerase chain reaction (RT‐PCR) (16 cases) as a first step toward understanding the metabolism and possible actions of androgens in human common epithelial ovarian carcinoma. 5α‐Reductase type 1 was immunopositive in 75/104 cases (72.0%), and 5a‐reductase type 2 in 52/104 cases (50.0%) (P<0.001). There was no significant correlation between patterns of immunolocalization and clinicopathological parameters examined. Median labeling index (LI) for AR was 17.8% (range 0‐84.4%) which was significantly higher in serous carcinoma than other histological types (P<0.001). There was a significant positive correlation between 5α‐reductase type 1 immunoreactivity and AR LI (P=0.0027), but no significant correlation was detected in 5α‐reductase type 2. Results of RT‐PCR analysis were also consistent with those of immunohistochemistry. The relatively wide distribution of 5a‐reductase type 1, and its correlation to AR status in human epithelial ovarian malignancies suggest that this isozyme plays important roles in androgen metabolism and actions in these tumors.

Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer, in part because of the lack of effective early detection methods. Although alterations of several genes, such as c-erb-B2, c-myc, and p53, have been identified in a significant fraction of ovarian cancers, none of these mutations are diagnostic of malignancy or predictive of tumor behavior over time. Here, we used oligonucleotide microarrays with probe sets complementary to >6,000 human genes to identify genes whose expression correlated with epithelial ovarian cancer. We extended current microarray technology by simultaneously hybridizing ovarian RNA samples in a highly parallel manner to a single glass wafer containing 49 individual oligonucleotide arrays separated by gaskets within a custom-built chamber (termed "array-of-arrays"). Hierarchical clustering of the expression data revealed distinct groups of samples. Normal tissues were readily distinguished from tumor tissues, and tumors could be further subdivided into major groupings that correlated both to histological and clinical observations, as well as cell type-specific gene expression. A metric was devised to identify genes whose expression could be considered ideal for molecular determination of epithelial ovarian malignancies. The list of genes generated by this method was highly enriched for known markers of several epithelial malignancies, including ovarian cancer. This study demonstrates the rapidity with which large amounts of expression data can be generated. The results highlight important molecular features of human ovarian cancer and identify new genes as candidate molecular markers.

P53 mutation does not affect prognosis in ovarian epithelial malignancies.

Mutations of the p53 tumour suppressor gene have been found in most human cancers, including ovarian epithelial malignancies. This study investigated whether the presence or absence of p53 mutation was associated with outcome following platinum-based chemotherapy in patients with ovarian cancer. DNA samples from tumour tissue and blood were obtained from 73 patients with primary tumours, 50 of whom received platinum-based adjuvant chemotherapy. Single-strand conformation polymorphism analysis and direct DNA sequencing of exons 5-8 detected mutations in 44% (32 of 73) of tumours. These were more common in late-stage (III or IV) than in early-stage disease (I or II) (p=0.03). There was no association with histological type, volume of residual disease following surgery, or initial CA125 levels. No significant association was found between p53 status and overall survival or disease-free survival following chemotherapy. Likewise, there was no correlation between p53 mutation and response to chemotherapy as defined by normalization of CA125 levels. Tumours with p53 missense mutations recurred within a significantly shorter time than those with normal p53 (p=0.04). In addition, there was a tendency for tumours with missense mutations to have a shorter disease-free survival than those with non-missense mutations, although this did not reach statistical significance (p=0.07).

P21/WAF1 expression as related to p53, cell proliferation and prognosis in epithelial ovarian cancer.

The role and prognostic value of the tumour suppressor p21/WAF1 expression in epithelial ovarian cancer has not yet been defined. Therefore, the expression of p21/WAF1 was assessed immunohistochemically (IHC) in 316 epithelial ovarian malignancies in relation to p53, cell proliferation and patient survival. p21/WAF1 expression was inversely correlated with p53 and cell proliferation. Low p21/WAF1 expression was significantly associated with high grade of the tumour (P = 0.0005), advanced FIGO stage (P = 0.001) and primary residual tumour (P = 0.0001). Low p21/WAF1 expression was a marker of poor overall survival (P = 0.012). Similarly, p53-positivity and high cell proliferative activity were significant predictors of poor survival in univariate analyses. Moreover, the patients with p21–/p53+ tumours had a poorer overall (P < 0.00005) and recurrence-free (P = 0.0005) survival in univariate analyses, and the p21/p53 expression independently predicted tumour recurrence in Cox's multivariate analysis. Our results suggest that p21/WAF1 expression is mostly p53-dependent in epithelial ovarian cancer. High p21/WAF1 expression seems to function as a negative cell cycle regulator and as a marker of favourable disease outcome in epithelial ovarian cancer. In addition, the patients with their tumour expressing no or low p21/WAF1 protein but positive for p53 had a notably higher risk of recurrent disease, implicating that these patients might be more prone to treatment failures. © 1999 Cancer Research Campaign

Failure to Demonstrate Human Papillomavirus DNA in Epithelial Ovarian Cancer by General Primer PCR

One of the recent controversies with substantial clinical interest is the role of HPV in pathogenesis of ovarian cancer. The available highly conflicting data are based on analysis of 175 ovarian carcinomas so far. As an attempt to further elucidate this issue, the first systematic study of HPV detection in ovarian cancer was carried out using a highly sensitive general primer PCR (confirmed by hybridization for low- and high-risk HPV types separately) in a series of 98 histologically and clinically well-characterized epithelial ovarian malignancies. Despite the high (fg) sensitivity and a wide HPV type coverage of the technique used, all 98 ovarian carcinomas failed to demonstrate any signs of HPV DNA whatsoever. The preexisting 12 reports comprising a total of 175 ovarian tumors analyzed for HPV were summarized, giving highly discrepant results (i.e., detection rates from 0 to 100%) with the overall HPV DNA detection rate of 25.7%. The reasons for these discrepant findings are most probably technical. Our data are consistent with those of the majority of the most recent reports failing to disclose HPV DNA in ovarian neoplasia. The present completely negative results make the authors inclined to conclude that HPV is highly unlikely to play any causal role in the pathogenesis of epithelial ovarian neoplasia.

In VitroSensitivity of Fresh Ovarian Carcinoma Specimens to CPT-11 (Irinotecan)

Objective.Irinotecan (CPT-11) is a DNA topoisomerase I inhibitor which has shown activityin vitroagainst several cancer cell lines and some promising clinical responses in phase I and II trials in various solid tumors. The cytotoxicity of CPT-11 on human ovarian epithelial malignancies was testedin vitroutilizing the ATP chemosensitivity assay. Flow cytometry was also performed on the fresh carcinoma specimens.Methods.Fresh tumor samples were obtained at laparotomy from 20 patients with primary adenocarcinoma of the ovary and 1 patient with heavily pretreated recurrent ovarian carcinoma. Tumors were plated in anin vitrosystem and treated with varying doses of both CPT-11 and its active metabolite SN-38 (7-ethyl-10-hydroxycamptothecin), in addition to a panel of standard chemotherapeutic agents used in treating ovarian cancer. On the sixth day after incubation, ATP levels in remaining cells were measured using a luminometer as an indication of the amount of cell kill compared to untreated controls.Results.Twelve of the 21 tumors were evaluable for a response to CPT-11. Of the 12 tumors tested, 7 were found to have median effect doses of CPT-11 significantly under the clinically achievable peak plasma concentration (range 1.00 × 10−4to 44.67 μM) and 11 of the 12 tumors showed sensitivity to the active metabolite SN38 with median effect doses ranging from 2.00 × 10−4to 0.147 μM. Some of these tumors showed resistance to the standard agents, such as platinum, based on our assay. The heavily pretreated recurrent tumor tested was very sensitive to both CPT-11 and SN38 by our assay. The results of flow cytometry showed that the tumors were composed of heterogeneous populations of cells with mean S phase fractions varying from 7.0 to 17.3%. The only tumor not sensitive to SN38 showed the highest mean S phase activity of 17.3%.Conclusions.Overall, these results suggest that CPT-11 deserves further investigation as a clinically useful chemotherapeutic agent for ovarian cancer.

The role of CA 125 in screening for ovarian cancer.

Ovarian cancer has the worst prognosis of any gynaecological malignancy, primarily because it tends to present at an advanced stage. The excellent survival rates of early stage disease have provided the rationale for efforts to detect ovarian cancer early by screening, in the hope that survival rates will be improved. Available data suggests that CA 125 is elevated in the majority of epithelial ovarian malignancies prior to clinical presentation. Large trials of screening for ovarian cancer indicate that using a CA 125 cutoff value of 30 U/mL has good sensitivity, but inadequate specificity for detecting preclinical disease. Use of transvaginal ultrasonography as a second-line test in women with elevated CA 125 levels improves specificity to acceptable levels, as does use of a mathematical algorithm which analyses rates of change of CA 125. Two major randomised controlled trials, investigating the effect of screening strategies incorporating CA 125 on mortality, are currently underway.

Mucinous ovarian adenocarcinoma in the premenarchal patient: a case presentation

Epithelial ovarian malignancies are uncommon prior to the menarche. Mucinous cystadenocarcinomas are rare in children and tend to present with advanced disease. A case is described of malignant mucinous cystadenocarcinoma of the ovary occurring in a premenarchal girl resulting in intestinal obstruction. There was a fatal outcome despite multimodal therapy, which included ablative surgery. Familial recurrence of site-specific ovarian cancer requires counselling and follow-up of the female siblings of children with aggressive tumors.