Comparison of epidemiological factors between serous and mucinous borderline ovarian tumors: therapeutic implications

The goals of this multicenter French retrospective study were to compare epidemiological factors within borderline ovarian tumors (BOT) according to their serous (SBOT) or mucinous (MBOT) type and according to the presence of pejorative histological criteria. We analysed 224 SBOT and 164 MBOT diagnosed between 1990 and 2009. The patients mean age was not different according to serous or mucinous type (46.9 ± 16.7 years and 44.6 ± 17.6 years). Women with SBOT, had more frequently history of infertility (17.2% versus 3.9%, P < 0.0001) than women with MBOT. SBOT were more often asymptomatic (52.3% versus 33.5%, P < 0.001), bilateral (26.4% versus 4.3%, P = 0.0001), smaller (9.1 cm versus 14.5 cm, P = 0.0001) and diagnosed at advanced stage (81.2% of stage I versus 95.1%, P < 0.0001) than MBOT. The micropapillary pattern found in 10.3% of SBOT was observed at younger age (38 ± 15.4 years versus 47.9 ± 16.6 years, P = 0.007) and was more often associated with peritoneal implants (26.1% versus 6.5%, P = 0.02). The intraepithelial carcinoma found in 6.7% of MBOT, was more often associated with micro-invasion (36.4% versus 4.6%, P = 0.003). The existence of epidemiologic differences between SBOT and MBOT underlines that the BOT series analysis can not be considered without taking into account this parameter.     

Influence of histological subtypes on the risk of an invasive recurrence in a large series of stage I borderline ovarian tumor including 191 conservative treatments

BackgroundThe overall prognosis of stage I borderline ovarian tumors (BOT) is excellent but a small percentage of patients die to their disease. The prognostic factors for such a rare event are still not clearly defined. The aim of this study was to determine these factors for recurrence per se and recurrence in the form of invasive carcinoma in a large series of stage I tumors.MethodsA retrospective review of patients with BOT. Three inclusion criteria were defined: (i) a centralized histological review; (ii) macroscopic stage I tumors; (iii) exclusion of metastatic disease to the ovaries.ResultsFrom 2000 to 2010, 254 patients fulfilled inclusion criteria [140 had mucinous BOT (MBOT) and 114 a serous BOT (SBOT)], and 191 had undergone conservative management. After a median follow-up of 45 months, 43 patients had developed recurrences (31 borderline and 12 invasive).The risks of recurrences were statistically increased after conservative treatment, particularly after a cystectomy, in patients with stage IB and among patients with incompletely staged tumors. In the subgroup of conservatively treated patients (representing 75% of our population), the risks of recurrences were statistically increased in patients affected by a SBOT, in patients who had undergone a cystectomy, in patients with stage IB disease and in patients with a micropapillary pattern (MPP). MBOT and the presence of a MPP were identified as prognostic factors for invasive disease.ConclusionsIn the present series of BOT with the largest number of patients treated conservatively to date, the presence of a MPP and the mucinous subtype were associated with a higher rate of progression to carcinoma after conservative management. These important results suggest that MBOT belong to a ‘high-risk’ group likely to develop an invasive recurrence after fertility-sparing surgery in stage I BOT.     

Selection of carbohydrate antigens in human epithelial ovarian cancers as targets for immunotherapy: serous and mucinous tumors exhibit distinctive patterns of expression

Expression of blood group-related carbohydrate antigens was examined in frozen sections from a series of ovarian carcinomas of different histological types using an indirect immunoperoxidase technique. Antigenic specificities belonging to the O(H) and Lewis blood group families (H-1, H-2, Le(a), sLe(a), Le(x), sLe(x), Le(b) and Le(y)) or the mucin-core family (Tn, sTn and TF) were studied. A distinct difference in antigen expression between mucinous and other ovarian carcinomas (serous and endometrioid) was observed. Specifically, mucinous tumors tended to express sTn, Le(a) and sLe(a) strongly and homogeneously, whereas serous and endometrioid tumors rarely expressed these specificities and, in contrast, expressed Le(y) and H type 2 antigen strongly. When expressed in serous tumors, sTn was usually distributed in a heterogeneous pattern, whereas sTn expression in mucinous tumors was much more homogeneous. The distribution of Le(y) in serous tumors was noticeably homogeneous. H-1, Le(x), sLe(x), Le(b), TF and Tn specificities were rarely expressed in any type of ovarian carcinoma. Our results provide further support for the different histogenesis of mucinous and non-mucinous tumors and indicate alternative differentiation pathways for the 3 pathological subtypes of ovarian tumor. They also provide the basis for the choice of carbohydrate antigens for active and passive immunotherapy of ovarian carcinomas.     

Body size and risk of epithelial ovarian and related cancers: a population-based case-control study

Different subtypes of ovarian cancer appear to have different causes; however, the association between body mass index (BMI) and the different subtypes is unclear. We examined the associations between body-mass index (BMI) and weight gain and risk of the different histological subtypes of epithelial ovarian cancer in a case-control study in Australia. Cases aged 18-79 with a new diagnosis of invasive epithelial ovarian cancer (n = 1,269) or borderline tumor (n = 311) were identified through a network of clinics and cancer registries throughout Australia. Controls (n = 1,509) were selected from the Electoral Roll. Height and weight (1 year previously, at age 20 and maximum weight) and other risk factor information were ascertained via a self-administered questionnaire. Obesity was positively associated with clear cell tumors (Odds Ratio 2.3; 95% confidence interval 1.2-4.2) but not invasive endometrioid or mucinous tumors. Although there was no association with invasive serous tumors overall (0.9; 0.7-1.2), we did see an increased risk of serous peritoneal tumors (2.9; 1.7-4.9), but not of serous tumors of the ovary and fallopian tube. Of the borderline subtypes, obesity was positively associated with serous (1.8; 1.1-2.8) but not mucinous tumors (1.1; 0.7-1.7). Overweight was not associated with any subtype overall. There was no association with BMI at age 20, or weight gain for any of the histological subtypes. These results add to the current evidence that obesity increases a woman's risk of developing distinct histological subtypes of ovarian cancer.     

Ovarian cancer histology-specific incidence trends in Canada 1969-1993: age-period-cohort analyses.

This study examined histology-specific incidence trends of ovarian cancer in Canada, 1969-1993. The impact of age, period and cohort effects on these trends were studied by means of age-period-cohort analysis. Age-standardized incidence rates of serous, endometrioid, clear cell and germ cell tumours increased significantly and the rates of sex cord-stromal and other classified epithelial ovarian tumours decreased considerably. The rates of mucinous and NOS/unclassified tumours remained unchanged. Cohort effect has a major impact on incidence trends of serous, endometrioid, germ cell, sex cord-stromal and other classified epithelial ovarian tumours but no meaningful impact on trends of mucinous, clear cell, or NOS/unclassified ovarian tumours. Various cohort patterns by histology subtypes were observed: the risk of developing serious tumours increased markedly among birth cohorts of 1895-1930, stabilized thereafter and decreased among young cohorts of 1950-1960; the risk of germ cell tumours increased significantly among young cohorts of 1965-1980; and the risk of sex cord-stromal tumours dropped constantly among cohorts 1910-1950. Various period patterns by histology subtypes observed in this study suggested changes in histology classification criteria over the period. Further studies need to consider the various etiologies and the classification criteria changes according to histology subtypes.     

Risk of specific types of ovarian cancer after borderline ovarian tumors in Denmark: A nationwide study

Population-based evidence regarding risk of ovarian cancer after a borderline ovarian tumor (BOT) is sparse. We aimed to examine the incidence of specific types of ovarian cancer in women with serous or mucinous BOTs in a nationwide cohort study with up to 36 years of follow-up. Using the nationwide Danish Pathology Data Bank, we identified 4,281 women with a BOT (2,058 serous BOTs and 2,223 mucinous BOTs) in Denmark during 1978–2012. We computed standardized incidence ratios (SIRs) to compare the incidence of ovarian cancer among women with BOTs compared to general population rates. We found that a serous BOT was especially and strongly associated with subsequent serous ovarian cancer (SIR = 9.2; 95% CI: 6.8–12.2), and that a mucinous BOT was strongly related to mucinous ovarian cancer (SIR = 18.6; 95% CI: 10.8–29.8). The SIRs remained elevated ≥10 years after a serous BOT and up to 5–9 years after a mucinous BOT. The increased incidence of serous ovarian cancer in women with a serous BOT was mostly pronounced in women <50 years at the serous BOT diagnosis. In conclusion, women with a serous BOT experience long-term increased incidence of serous ovarian cancer, and women with a mucinous BOT have long-term elevated incidence of mucinous ovarian cancer compared to the general population. This is the first population-based study to show compelling evidence of the histo-specific increased risk of ovarian cancer following specific types of BOTs. Thus, these results are supportive of the hypothesis that BOTs may be precursor lesions to carcinomas of the corresponding histologic type.     

Proteomic characterization of ovarian cancers identifying annexin-A4, phosphoserine aminotransferase, cellular retinoic acid-binding protein 2, and serpin B5 as histology-specific biomarkers

Numerous studies have suggested that the different histological subtypes of ovarian carcinoma (i.e. clear cell, endometrioid, mucinous, and serous) have distinct clinical histories and characteristics; however, most studies that have aimed to determine biomarker have not performed comprehensive analyses based on subtype specificity. In the present study, we performed two-dimensional gel electrophoresis-based differential proteomic analysis of the different histological subtypes of ovarian carcinoma using tissue specimens from 39 patients. Seventy-seven protein spots (55 unique proteins) were found to be up- or downregulated in a subtype-specific manner. The most significant difference was observed for: (i) annexin-A4 (ANXA4) and phosphoserine aminotransferase (PSAT1), which are expressed strongly in clear cell carcinoma; (ii) cellular retinoic acid-binding protein 2 (CRABP2), which is expressed specifically in serous carcinoma; and (iii) serpin B5 (SPB5), which is upregulated in mucinous carcinoma. Validation of these candidates by western blotting using a 34 additional test sample set resulted in an expression pattern that was consistent with the screening and revealed that differential expression was independent of cancer stage or tumor grade within each subtype. Thus, the present study reinforces the notion that ovarian cancer subtypes can be clearly delineated on a molecular basis into four histopathological groups, and we propose that ANXA4, PSAT1, CRABP2, and SPB5 are candidate subtype-specific biomarkers that can help define the basis of tumor histology at a molecular level.     

Ovarian cancer risk factors by histologic subtypes in the NIH-AARP Diet and Health Study

Data suggest that risk factors for ovarian carcinoma vary by histologic type, but findings are inconsistent. We prospectively evaluated risk factors by histological subtypes of incident ovarian cancer (n = 849) in a cohort of 169,391 women in the NIH-AARP Diet and Health Study. We constructed Cox models of individual exposures by comparing case subtypes to the entire non-case group and assessed p-heterogeneity in case-case comparisons using serous as the reference category. Substantial risk differences between histologic subtypes were observed for menopausal hormone therapy (MHT) use, oral contraceptive (OC) use, parity and body mass index (p-heterogeneity = 0.01, 0.03, 0.05, 0.03, respectively). MHT users were at increased risk for all histologic subtypes except for mucinous carcinomas, where risk was reduced (relative risk (RR) = 0.37; 95% confidence interval (CI): 0.18, 0.80). OC users were only at significantly decreased risk for serous cancers (RR = 0.69; 95% CI: 0.55, 0.85). Although parity was inversely associated with risk of all subtypes, the RRs ranged from 0.28 (clear cell) to 0.83 (serous). Obesity was a significant risk factor only for endometrioid cancers (RR = 1.64; 95% CI: 1.00, 2.70). Our findings support a link between etiological factors and histological heterogeneity in ovarian carcinoma.     

保守性手术对交界性卵巢肿瘤预后及生育功能的影响

目的；研究首次行保守手术后交界性卵巢肿瘤（BOT）患者的生育功能和疾病结局。方法：对自1990年1月－2000年5月在我院住院43例符合筛选条件的BOT患者行问卷调查及回顾性病例分析，采用SAS软件包对数据进行处理。结果：43例病人中，41例病人完成问卷调查，26例为浆液性交界性卵巢肿瘤（SBOT）；17例为粘液性交界性卵巢肿瘤（MBOT），平均随访时间是63个月，术后无肿瘤复发29例，肿瘤复发14例（包括1例死于肿瘤复发，1例死于其它疾病），平均复发时间是术后39．3个月。卵巢肿瘤剥除术后肿瘤复发率58．3％（7／12），而卵巢切除术后肿瘤复发率22．6％（7／31），两者差异有显著性（Fisher精确概率P＝0．0351），但保守手术后肿瘤复发死亡率并不高于根治性手术（P＝0．64），术后24例有生育愿望的妇女，12例获得妊娠，妊娠年龄范围23－34岁，平均25岁，结论：保守手术可作为BOT患者的一种治疗选择；尽管术后肿瘤复发率较高（33％，14／43），尤其是行卵巢肿瘤剥除术的病人，但肿瘤复发死亡率并未增加；术后有妊娠愿望者能够再次妊娠并分娩正常后代。     

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Survival of Ovarian Cancer in Iran: 2000-2004

Objective: The aim of this study was to estimate the 5-year survival of ovarian cancer in Iran between 2000and 2004, according to age and histology. Methods: Cancer registry of Iran, 2000-2004, was used coveringnearly 80% of all ovarian cancers and 100% of all pathologically diagnosed ovarian cancers. Results: Of 1,246new ovarian cancer cases, 451 were available for further follow-up which revealed 169 deaths and 282 live cases.The 5-year survival was 61%; 85% for germ cell tumors and 59% for epithelial tumors. Survival of serous,mucinous, endometrioid and clear cell histologic subtypes of epithelial tumors was 41%, 62%, 76% and 78%,respectively. Young patients with epithelial tumors (below 45) displayed significantly better 5-year survivalrates (63% versus 53%). Conclusion: we found that ovarian cancer had a better survival rate in Iran in comparisonto other regions. We also reviewed all probable confounding factors or real causes. In this study, age and histologyaffected survival.     

ABCC4/MRP4 contributes to the aggressiveness of Myc-associated epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is a complex disease comprising discrete histological and molecular subtypes, for which survival rates remain unacceptably low. Tailored approaches for this deadly heterogeneous disease are urgently needed. Efflux pumps belonging to the ATP-binding cassette (ABC) family of transporters are known for roles in both drug resistance and cancer biology and are also highly targetable. Here we have investigated the association of ABCC4/MRP4 expression to clinical outcome and its biological function in endometrioid and serous tumors, common histological subtypes of EOC. We found high expression of ABCC4/MRP4, previously shown to be directly regulated by c-Myc/N-Myc, was associated with poor prognosis in endometrioid EOC (P = .001) as well as in a subset of serous EOC with a “high-MYCN” profile (C5/proliferative; P = .019). Transient siRNA-mediated suppression of MRP4 in EOC cells led to reduced growth, migration and invasion, with the effects being most pronounced in endometrioid and C5-like serous cells compared to non-C5 serous EOC cells. Sustained knockdown of MRP4 also sensitized endometrioid cells to MRP4 substrate drugs. Furthermore, suppression of MRP4 decreased the growth of patient-derived EOC cells in vivo. Together, our findings provide the first evidence that MRP4 plays an important role in the biology of Myc-associated ovarian tumors and highlight this transporter as a potential therapeutic target for EOC.     

Endometrioid epithelial ovarian cancer : 20 years of prospectively collected data from a single center

BACKGROUND: Clinicopathological features and outcome of women with endometrioid and serous ovarian adenocarcinoma were compared. METHODS: Between 1984 and 2004, baseline and follow-up data were prospectively recorded on 1545 patients with ovarian cancer. Of these, 270 had pure endometrioid tumors; 659 had pure serous adenocarcinoma of the ovary. Response to platinum-based chemotherapy (PBC) overall survival, stage-for-stage median progression-free survival (PFS), and cause-specific median survival were compared. Independent predictors of survival were examined by using multivariate analyses. RESULTS: Median age of diagnosis for patients with endometrioid tumors was younger than those with serous adenocarcinoma of the ovary (60 years vs 62 years; P = .013). They presented more often with early disease (stage I and II; 50% vs 17%; P < .001), had less ascites, and had better performance status both overall and for stage II and III disease. More endometrioid tumors were optimally debulked overall (71% vs 45%; P < .001), but there was no difference according to stage. Objective and CA125 PBC response rates were not significantly different, but median PFS was better for patients with endometrioid tumors (24 months vs 13 months; P < .0001) as was overall median survival (48 months vs 22 months; P < .0001). This relation remained for stage II and III disease and for moderately and poorly differentiated tumors. Patients with concurrent endometrioid ovarian and endometrial malignancies had a survival advantage compared with those with ovarian malignancies alone. Independent predictors of survival after PBC were histological type, debulking status, and disease stage. CONCLUSIONS: Despite similar PBC response rates, endometrioid histology is associated with better survival compared with serous adenocarcinoma of the ovary, even with stage III or poorly differentiated tumors.     

Cigarette smoking and risk of histological subtypes of epithelial ovarian cancer in the EPIC cohort study

New data regarding a positive association between smoking and risk of epithelial ovarian cancer (EOC), especially the mucinous tumor type, has started to emerge. The purpose of this study was to examine the association between different measures of smoking exposures and subtypes of EOC in a large cohort of women from 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort is a multicenter prospective study initiated in 1992. The questionnaires included data about dietary, lifestyle, and health factors. Information about cigarette smoking was collected from individuals in all participating countries. We used Cox proportional hazard regression models to estimate hazard ratio (HR) of EOC overall and serous, mucinous, and endometroid histological subtypes, with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 836 incident EOC cases were identified among 326,831 women. The tumors were classified as 400 serous, 83 mucinous, 80 endometroid, 35 clear cell, and 238 unspecified. Compared with never smokers, current smokers had a significantly increased risk for mucinous tumors [HR = 1.85 (95% CI 1.08-3.16)] and those smoking more than 10 cigarettes per day had a doubling in risk [HR = 2.25(95% CI 1.26-4.03)] as did those who had smoked less than 15 pack-years of cigarettes [HR = 2.18 (95% CI 1.07-4.43)]. The results from the EPIC study add further evidence that smoking increases risk of mucinous ovarian cancer and support the notion that the effect of smoking varies according to histological subtype.     

Expression profile of histone deacetylases 1, 2 and 3 in ovarian cancer tissues

Objective

To investigate the expression levels of histone deacetylase (HDAC) 1, 2, and 3 in ovarian cancer tissues and normal ovarian tissues.

Methods

Randomly assigned each of six patients with serous, mucinous and endometrioid ovarian cancer were included. Another six patients with normal ovarian tissue were included for comparison. RT-PCR was performed to quantify the levels of HDACs1-3 mRNA in the cancer and normal tissues. Western blot analysis was performed to measure the expression levels of HDACs1-3 protein. The HDACs1-3 expression pattern was also topologically examined by immunohistochemistry.

Results

Increased mRNA expressions of HDCA1, HDAC 2 and HDAC 3 were detected in 83%, 67% and 83% of 18 cancer tissue samples, compared to normal tissue samples. The relative densities of HDAC1 mRNA and HDAC3 mRNA in the serous, mucinous and endometrioid cancer tissues, and HDAC2 mRNA in serous cancer tissues were significantly higher than those of the normal tissues, respectively (p<0.05). Overexpression of HDAC1, HDAC2 and HDAC3 proteins were detected in 94%, 72% and 83% of 18 cancer samples, respectively. The relative densities of HDAC1 protein and HDAC3 protein in serous, mucinous and endometrioid cancer, and HDAC2 protein in serous and mucinous cancer tissues were significantly higher than those of normal tissues, respectively (p<0.05). Most cancer tissues expressed moderate to strong staining of HDACs1, 2 and 3 in immunohistochemistry. Staining of HDAC2 was weak in only one endometrioid cancer tissue.

Conclusion

HDACs1-3 are over expressed in ovarian cancer tissues and probably play a significant role in ovarian carcinogenesis.     

Identification of two different surface epitopes of human ovarian epithelial carcinomas by monoclonal antibodies

Monoclonal antibodies (Mabs) against human ovarian mucinous and serous carcinoma were obtained by the Mab technique. Their reactivities against human tumors were tested by indirect immunofluorescence. One of the Mabs, named 4C7, derived from the spleen cells of mice immunized with mucinous carcinoma line OVA-1, reacted to ovarian mucinous carcinoma, endometrioid carcinoma, and mesonephroid carcinoma but did not react to ovarian serous carcinoma. Another Mab, 3C2, obtained from the spleen cells of mice immunized with serous carcinoma line HOC-21, reacted to serous carcinoma and endometrioid carcinoma of ovary, but never reacted to mucinous carcinoma or mesonephroid carcinoma. Neither of the Mabs reacted to other types of ovarian carcinomas such as undifferentiated carcinoma, dysgerminoma, endodermal sinus tumor, and malignant teratoma of ovary, and also did not react to any benign ovarian tumors or other normal human tissues. Both Mabs 3C2 and 4C7 had no reactivity to carcinoma of other organs such as stomach, colon, lung, lymphoid system, and kidney and also did not react to human lymphocytic or carcinoembryonic antigen as confirmed by using many human cell lines and surgically resected samples. Since the cross-reactivities of these Mabs were limited within the ovarian epithelial carcinomas, it is suggested that two distinct epitopes are expressed on the ovarian epithelial carcinomas. One epitope, identified by Mab 4C7, is expressed only on mucinous carcinoma, endometrioid carcinoma, and mesonephroid carcinoma, while the epitope, identified by Mab 3C2, appears only on serous and endometrioid carcinoma.     

Aktuelle Aspekte zur Tumorigenese und Ätiologie

Background and aim

The concepts of the pathogenesis of epithelial ovarian tumors have significantly changed during the last decade. The aim of this review is to briefly present the current concepts on this topic.

Methods

This work is based on a selective PubMed search using the terms “ovarian” cancer and “origin”.

Results

Numerous studies have shown that the histological subtypes of ovarian cancer greatly differ in molecular features, etiology, therapy response, and prognosis. Correlations between histopathological and molecular characteristics revealed that serous tubal intraepithelial carcinoma (STIC) is probably the precursor of high grade serous carcinoma, and that endometrioid and clear cell carcinomas arise in ovarian endometriosis cysts. Preliminary data also point to a tubal origin of low grade serous carcinoma while the pathogenesis of rare mucinous neoplasia is currently unclear.

Conclusions

The histological subtypes of ovarian cancer should be considered as separate entities. The origin of most epithelial ovarian neoplasia very probably lies in extraovarian organs.

     

Evidence for divergence of DNA copy number changes in serous, mucinous and endometrioid ovarian carcinomas.

Comparative genomic hybridization was applied to detect and map changes in DNA copy number in 24 well or moderately differentiated epithelial ovarian carcinomas (eight serous, eight mucinous and eight endometrioid carcinomas). Twenty-three of the 24 tumours showed changes in DNA copy number in one or several regions (median 4, range 1-17). Gains were more frequent than losses (ratio 1.6:1.0). The most frequent gains occurred in chromosomes 1q (38%), 2p (29%), 7q (25%), 8q(38%) and 17q (38%), and the most common losses were located in chromosomes 8p (21%), 9p (25%) and 13q (21%). High-level amplifications were detected in seven tumours at 1q22-32, 2p15-22, 3qcen-23, 6p21-22 and 8q. In the three histological subtypes the copy number karyotypes showed substantial differences. Gains at 1q were observed in endometrioid (five cases) and serous tumours (four cases). Increased copy number at 10q was seen in endometrioid tumours only (four cases), whereas gains at 11q occurred mostly in serous tumours (four cases). In mucinous tumours, the most common copy number change was a gain at 17q (six cases). The results show that, in epithelial ovarian carcinoma, changes in DNA copy number are a rule rather than an exception, chromosomes 1, 2, 7, 8, 9, 13 and 17 being the most frequently affected. The diverging pattern of genetic changes seen in epithelial ovarian carcinomas with different histological phenotypes suggests that various pathways may lead to tumorigenesis and/or progression in these subgroups.     

Common epithelial ovarian tumors. Immunohistochemical intermediate filament profiles

The authors studied 79 common epithelial ovarian tumors in order to ascertain the intermediate filament profiles in formalin-fixed and methacarn-fixed, paraffin-embedded surgical pathology materials. Ultra-structural correlations were attempted with several tumors. All categories of common benign and malignant epithelial tumors were examined. Antibodies used in the study included antikeratins (AE1/AE3, 35BH11, 34BE12), carcinoembryonic antigen (CEA), and vimentin. All ovarian epithelial tumors expressed keratin in uniform fashion, except high molecular weight keratin (34BE12) which was focal. Vimentin was coexpressed with cytokeratins in 42% of serous carcinomas, 71% of endometrioid carcinomas, and 7% of clear cell carcinomas. Vimentin decoration in serous carcinoma was very focal, whereas endometrioid decoration tended to involve larger areas, similar to uterine-based endometrial adenocarcinoma. Mucinous, Brenner, and solid (not otherwise specified) ovarian tumors were positive only for cytokeratin. Carcinoembryonic antigen luminal staining was present in 52% of serous carcinomas and 87% of mucinous carcinomas. Whereas there are distinct differences in intermediate filament expression among ovarian carcinomas, these differences do not allow for specific categorization of ovarian neoplasms because there is some overlap of intermediate filament expression. In order to differentiate ovarian carcinoma from other carcinomas and mesothelioma, other methods of study would be necessary in addition to intermediate filament profiles, such as CEA immunohistochemistry, mucin histochemistry, and ultrastructural study.