Borderline ovarian tumors

Borderline ovarian tumors account for approximately 15% of all epithelial ovarian tumors. In the early 1970s, borderline tumors were categorized as either serous or mucinous with overall survival rates of 75–90%. Since then, it has been recognized that the two categories are heterogonous. There are now many different groups following the recognition of serous tumors with microinvasion, non‐invasive and invasive peritoneal implants and a micropapillary pattern, and of mucinous tumors with microinvasion, intraepithelial carcinoma and pseudomyxoma peritoneal implants, in addition to further delineation of endometrial, clear cell and transitional cell tumors with atypical proliferation. This review outlines the most recent information regarding the epidemiology, pathology and clinical management of borderline tumors. Surgical management to excise all visible tumors remains the cornerstone of therapy. Because borderline ovarian tumors often occur in reproductive‐age women, fertility is an important issue. Conservative surgery is a safe in carefully selected patients. Effective non‐surgical therapies are yet to be identified.     

Borderline epithelial tumours of the ovary--a retrospective analysis of 31 cases

Thirty one cases of epithelial borderline tumours of the ovary recorded over a period of six years were reviewed. The incidence of borderline tumours was 6% in relation to ovarian epithelial malignancies, with serous and mucinous types comprising three fourth of the lesions. The serous tumours were bilateral in 39%, revealed surface growth in 17% and had peritoneal implants in 11% of cases. The mucinous tumours were bilateral in 11% and had associated pseudomyxoma peritonei in 22% of cases. Nuclear grade appeared to correlate with extraovarian spread and surface growth in the serous borderline tumours, but not in the mucinous borderline tumours. The endometrioid borderline tumours and mixed epithelial borderline tumours were rare lesions. Twenty one patients (68%) presented in Stage-la. Surface growth correlated with recurrences. The prognosis remained good in serous borderline tumours even in the presence of implants as these were non-invasive. The mean disease free survival was 43.03 months. There was no statistical difference in disease free survival of patients with and without implants.     

Research Developments on the Histopathology and Prognostic Predictors of Serous Borderline Tumor of Ovary

Serous borderline tumor of ovary (SBT) includes two subtypes of typical serous borderline tumor and micropapillary variant, which have different histopathology features. Although SBTs behave in either way of the benign counterparts or malignant serous carcinomas, microinvasion,peritoneal implants, and nodal involvement are all very common in both subtypes of typical SBT and the micropapillary variant.The prognosis of the patients with serous borderline tumor of ovary and the mechanism of the microinvasion, peritoneal implantation and nodal involvement are still being debated, nor is there universal agreement about the management of SBT. To identify the histopathologic features, prognostic predictors of the SBT, and its association with ovarian serous carcinomas, we reviewed the majority of the relevant papers published in recent literature.     

Research developments on the histopathology and prognostic predictors of serous borderline tumor of ovary

Serous borderline tumor of ovary （SBT） includes two subtypes of typical serous borderline tumor and micropapillary variant, which have different histopathology features. Although SBTs behave in either way of the benign counterparts or malignant serous carcinomas, microinvasion, peritoneal implants, and nodal involvement are all very common in both subtypes of typical SBT and the micropapillary variant. The prognosis of the patients with serous borderline tumor of ovary and the mechanism of the microinvasion, peritoneal implantation and nodal involvement are still being debated, nor is there universal agreement about the management of SBT. To identify the histopathologic features, prognostic predictors of the SBT, and its association with ovarian serous carcinomas, we reviewed the majority of the relevant papers published in recent literature.     

Pathology of ovarian carcinoma

Serous carcinoma is the most common type of ovarian cancer and usually is associated with peritoneal metastases and poor survival except for meticulously staged patients with tumors confined to the ovaries. Endometrioid and clear cell carcinomas account for most nonserous carcinomas and more often present with low-stage disease; survival for the various cell types is similar when stratified by stage. Borderline ovarian tumors can be subdivided into benign and malignant neoplasms, and in the view of some experts, this renders the borderline category obsolete. Women with typical serous borderline tumors (atypical proliferative serous tumors) constitute most of these patients and have virtually 100% survival, unless invasive peritoneal implants are present. Micropapillary serous carcinomas (a less common variant, also called serous borderline tumor with a micropapillary pattern) and tumors with invasive implants behave similar to low-grade invasive carcinomas.     

Cytoplasmic and stromal expression of laminin γ 2 chain correlates with infiltrative invasion in ovarian mucinous neoplasms of gastro-intestinal type

Ovarian mucinous neoplasms of gastro-intestinal type (GI-type) are known to be a heterogeneous tumor composed of benign, borderline and non-invasive and invasive malignant lesions. The presence of infiltrative invasion is also known to be an important prognostic factor of this neoplasm. Laminin γ 2 chain, known to stimulate tumor cell invasion and migration, has not been sufficiently investigated in ovarian mucinous neoplasms. The purpose of this study was thus to clarify the role of laminin γ 2 in ovarian mucinous neoplasms of GI-type. We selected each morphological phase of tumor development from 61 cases of mucinous neoplasms of the GI-type: 55 adenoma lesions, 60 borderline lesions, 20 microinvasive lesions, 17 intraepithelial carcinoma lesions, 38 expansile invasive carcinoma lesions, 19 infiltrative invasive carcinoma lesions and 5 mural nodules lesions; and evaluated the localization of laminin γ 2 in the lesions using immunohistochemical method. The staining pattern was classified into i) basement membranous (BM), ii) cytoplasmic (CYT) and iii) stromal (S) pattern. The BM pattern was characteristic in adenoma, borderline, and interaepithelial and expansile invasive carcinoma lesions. The CYT and S patterns were characteristic in infiltrative invasive lesions. The staining pattern of mural nodules was similar to that of infiltrative invasion. The infiltrative invasion of GI-type ovarian mucinous neoplasms may be promoted by cytoplasmic and/or stromal expression of laminin γ 2 chain.     

Borderline ovarian tumors diagnosed during pregnancy exhibit a high incidence of aggressive features: results of a French multicenter study

BackgroundThe purpose of the current study was to evaluate the characteristics of borderline ovarian tumors (BOTs) diagnosed during pregnancy.Patients and methodsWe conducted a retrospective multicenter study of 40 patients with BOTs diagnosed during pregnancy between 1997 and 2009 at five tertiary universitary departments of Gynecology and Obstetrics and one French cancer center. The medical records were reviewed to determine surgical procedure, histology, restaging surgery and recurrence.ResultsMean patient age was 30.2 ± 5.4 years. Most BOTs were diagnosed during the first trimester of pregnancy (62%). Salpingo-oophorectomy (N = 24) was more frequently performed than cystectomy (N = 11) during pregnancy (P = 0.01). Only two patients had an initial complete staging. BOTs were mucinous, serous and mixed in 48%, 42% and 10% of patients, respectively. Twenty-one percent of mucinous BOTs exhibited intraepithelial carcinoma or microinvasion. Forty-seven percent of serous BOTs exhibited micropapillary features, noninvasive implants or microinvasion. Restaging surgery performed in 52% patients resulted in upstaging in 24% of cases. Recurrence rate in patients with serous BOT with micropapillary features or peritoneal implants was 7.5%.ConclusionsBOTs diagnosed during pregnancy exhibit a high incidence of aggressive features and are rarely completely staged initially. Given this setting, up-front salpingo-oophorectomy should be considered and restaging planned.     

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.     

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.     

卵巢交界性黏液瘤和黏液癌近期病理学研究

卵巢交界性黏液瘤(mucinousborderline overian tumor,MBT)的病理诊断和生物学行为始终存在较多争论。目前,对于卵巢交界瘤有的仍按低度恶性肿瘤的治疗原则进行处理,结果多数患者接受过分的治疗。近期研究证实,MBT和它伴同的上皮内癌及微浸润癌在排除了腹膜假黏液瘤和转移癌后,预后良好。500例MBT经随访,死亡率为1%。分析死亡原因认为,肿瘤内存在的破坏性浸润未被发现或者将腹膜假黏液瘤及转移癌误诊为MBT,结果出现了死亡病例。MBT伴上皮内癌的诊断标准为腺上皮细胞增生至3~4层以上,胞核明显异形性,其生存率为100%。MBT伴微浸润的诊断标准是肿瘤间质内出现单个或呈巢状排列的癌细胞浸润,癌灶直径3~5mm,经随访无1例复发和死亡。卵巢黏液癌的浸润特点是“融合性和膨胀性浸润”,若出现间质浸润则要考虑为转移癌。卵巢黏液癌内有80%为转移癌。卵巢原发性和转移性癌的病理诊断除根据上述特征外,免疫组织化学染色有助于鉴别。     

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.     

Borderline tumours of the ovary: A cohort study of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Study Group

BackgroundBorderline ovarian tumours (BOTs) are recognised as a unique entity of ovarian tumours that do not exert infiltrative destructive growth or stromal invasion. Prognosis of BOT is much better compared to the more common invasive epithelial ovarian cancer. Information regarding prognostic factors is inconclusive and no prospective studies exist that evaluate therapeutic strategies. We therefore started a retrospective–prospective cohort study to better understand BOT and identify scenarios in which future studies could be developed.MethodsConsecutive patients with BOT treated between 1998 and 2008 in 24 German centres were analysed. The retrospective part of the study retrieved patients’ data from hospital records and clinical tumour registries while active follow-up and an independent central pathology review were carried out prospectively.FindingsBOT was confirmed in 950 patients, two thirds had serous BOT and 30.5% mucinous BOT. Most were diagnosed in stage I (82.3%); 7.6% and 10.1% had stages II and III, respectively. Overall, 74 patients (7.8%) experienced relapse and 43 (4.5%) died within the observation period. Multivariate analysis revealed higher stage, incomplete staging, tumour residuals, and organ preservation as independent prognostic factors for disease recurrence. Neither microinvasion nor micropapillary growth pattern showed any significant impact. Of 74 relapsed patients, 30% had malignant transformation to invasive ovarian cancer with five-year progression-free survival and overall survival of 12% and 50%, respectively.InterpretationPrognosis of BOT correlates with tumour-related as well as surgery-related factors. The balance between recurrence risk and organ preservation and fertility-sparing surgery is an important issue deserving further research.     

Expression of pro-apoptotic (p53, p21, bax, bak and fas) and anti-apoptotic (bcl-2 and bcl-x) proteins in serous versus mucinous borderline ovarian tumours

BACKGROUND: We examined the expression of apoptosis-related proteins in serous versus mucinous borderline ovarian tumours, in comparison with benign and malignant ovarian tumours. MATERIALS AND METHODS: Immunohistochemical expression of pro-apoptotic (p53, p21, bax, bak, fas) and anti-apoptotic proteins (bcl-2, bcl-x) was determined in 34 borderline (19 mucinous, 15 serous), 20 benign (10 mucinous, 10 serous) and 28 malignant ovarian tumours (9 mucinous, 19 serous). RESULTS: A difference in semi-quantitative p53 expression was found between benign and borderline tumours (P = 0.01), but not between borderline and malignant tumours. Increased p21 expression was found in borderline versus benign tumours (P = 0.004). Bcl-2 expression was lower in borderline than in benign (P = 0.01) and malignant tumours (P = 0.02). No difference in bax, bak, fas or bcl-x expression was observed among the three tumour types. Higher percentage of p21 positive cells was found in serous than in mucinous borderline tumours (P < 0.001). Bcl-2 expression was higher in serous than in mucinous forms of benign (P < 0.001), borderline (P < 0.001), and malignant tumours (P < 0.003). No difference in p53, bax, bak, fas or bcl-x expression was observed between serous and mucinous borderline ovarian tumours. CONCLUSION: Although p53 overexpression was a common feature of both mucinous and serous borderline tumours, p21 and bcl-2 overexpression appeared specific to serous tumours.     

Prognostic factors for recurrence after conservative treatment in a series of 119 patients with stage I serous borderline tumors of the ovary

BackgroundThe aim of this study was to evaluate prognostic factors for recurrence after conservative treatment of a large series of ‘apparent’ stage I serous borderline ovarian tumors (SBOTs).Patients and methodsA review of 119 patients treated conservatively between 2000 and 2009 with follow-up data. All pathological slides were reviewed by the same expert pathologist. Prognostic factors for recurrence were studied (age, histological subtypes and surgical procedure).ResultsConservative surgical procedures were: unilateral cystectomy (n = 43, 36%); unilateral adnexectomy (UA; n = 50, 42%); bilateral cystectomies (n = 11, 9%) and UA + contralateral cystectomy (n = 15, 13%). Stromal microinvasion and/or a micropapillary pattern was present in 21 (18%) and 13 (11%) patients, respectively. With a median follow-up of 45 months, 38 (32%) patients relapsed (10 also had peritoneal disease in the form of noninvasive implants at the first recurrence). In 2 of these 38 patients, progression-to-invasive disease occurred at the second and third relapse (one patient died to the recurrence). Three prognostic factors for recurrence were identified in the univariate analysis: a young age (< or >30 years old), the type of conservative treatment (adnexectomy versus cystectomy) and tumor bilaterality. In the multivariate analysis, only age remained statistically significant.ConclusionIn this series (the largest reported, to date, on recurrences after the conservative management of stage I SBOT), the risk of relapse was not related to tumor histological subtypes (micropapillary and stromal microinvasion) nor to the use of complete staging surgery. Invasive recurrences were very rare in stage I SBOT, but did occur. A young age, tumor bilaterality and the use of a cystectomy were identified as risk factors for recurrence, suggesting that management of fertility preservation (particularly in very young patients) should be associated with a meticulously conducted follow-up.     

Molecular Characterization of 103 Ovarian Serous and Mucinous Tumors

The pathogenesis of ovarian carcinomas is heterogeneous, with even the same entities showing great variance. In our study we investigated the mutations of the BRAF, KRAS, and p53 genes in serous and mucinous borderline tumors and in low grade and high grade serous and mucinous tumors. The mutations of BRAF and KRAS genes have been shown in 60% of borderline and low grade (well differentiated) serous and mucinous tumors, but very rarely in high grade (moderately and poorly differentiated) carcinomas. However mutations of p53 are very common in high grade tumors and this indicates a "dualistic" model of ovarian tumorigenesis. A total of 80 serous tumors, including serous borderline, low grade and high grade tumors, and 23 mucinous tumors, including borderline and invasive tumors were analysed for BRAF and KRAS mutations using real time PCR method followed by melting point analysis. P53 mutation was investigated by immunohistochemistry. We assumed mutation of the p53 gene when 100% of tumor cells showed strong nuclear positivity. We observed differences in genetic alterations in the development of the low grade tumors and between low and high grade tumors too. In some bilateral or stage II-III cases we observed differences between the mutation status of the left and right ovarian tumors and between the primary tumor and its implants. In one case in a tumor with micropapillary pattern showing high grade nuclear atypia we could detect mutations in both KRAS and p53 genes. The majority of our mucinous ovarian tumor cases showed a KRAS mutation. We have not found mutations of the BRAF and p53 genes in these cases. We have found as have others, that there is a dualistic pathway of ovarian carcinogenesis. In the majority of cases, low grade epithelial tumors develop in a stepwise manner due to genetic alterations of the members of MAP-kinase pathway; however mutation of the p53 gene is the key event in the development of high grade tumors.     

MDM2 Expression in Serous and Mucinous Epithelial Tumours of the Ovary

Background: Different types of cancer exhibit abnormalities in cell cycle regulators. The murine double minute2(MDM2) cell cycle regulator is a protooncogene that negatively regulates the P53 tumour suppressor gene. Surface epithelial tumours constitute approximately two thirds of ovarian neoplasms. Each histologic type can be classified as benign, borderline and malignant. This study aimed to examine immunohistochemical expression of the MDM2 protein in ovarian serous and mucinous epithelial tumours (benign, borderline and malignant). Materials and Methods: This study included forty five ovarian tumours, subdivided into fifteen cystadenomas (5 serous and 10 mucinous), fifteen borderline tumours (11 serous and 4 mucinous) and fifteen cystadenocarcinomas (9 serous and 6 mucinous). Paraffin sections were stained with haematoxylin and eosin for histopathologic study, and with mouse monoclonal antiMDM2 antibody for immunohistochemistry. Results: MDM2 positivity was detected in 28.9% of the studied ovarian tumours. All benign tumours were negative and positivity was significantly higher in malignant than borderline tumours (P value of chisquare test 0.000). Significantly, all MDM2 positive mucinous tumours were malignant with no positive mucinous borderline tumours. Malignant tumours showed positive MDM2 expression in 83.3% of mucinous type and in 55.6% of serous type. Borderline serous tumours showed negative MDM2 in 72.7% of cases (P value of Z test 0.04). Conclusions: Alterations in the expression of the cell cycle regulator (MDM2) occur early in the process of tumourigenesis in serous and mucinous ovarian tumours. We suggest that MDM2 may be used in those tumours as a marker for risk stratification and identification of cases with cancer development and progression. We recommend further studies on MDM2 immunohistochemistry, in conjunction with adjuvant methods as DNA ploidy and FISH gene amplification, focusing on the mucinous tumours and differentiating between the three tumour categories, benign, borderline and malignant.     

Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma

Activating mutations in KRAS and in one of its downstream mediators, BRAF, have been identified in a variety of human cancers. To determine the role of mutations in BRAF and KRAS in ovarian carcinoma, we analyzed both genes for three common mutations (at codon 599 of BRAF and codons 12 and 13 of KRAS). Mutations in either codon 599 of BRAF or codons 12 and 13 of KRAS occurred in 15 of 22 (68%) invasive micropapillary serous carcinomas (MPSCs; low-grade tumors) and in 31 of 51 (61%) serous borderline tumors (precursor lesions to invasive MPSCs). None of the tumors contained a mutation in both BRAF and KRAS. In contrast, none of the 72 conventional aggressive high-grade serous carcinomas analyzed contained the BRAF codon 599 mutation or either of the two KRAS mutations. The apparent restriction of these BRAF and KRAS mutations to low-grade serous ovarian carcinoma and its precursors suggests that low-grade and high-grade ovarian serous carcinomas develop through independent pathways.     

Time to reevaluate clinical trials for mucinous ovarian cancer

Invasive mucinous epithelial ovarian cancer (mEOC) accounts for approximately 10% of all epithelial ovarian cancers. There is evidence to suggest that the mucinous tumours are biologically distinct from the serous sub-type and are likely to evolve via an adenoma-carcinoma pathway. Recent studies looking at the genetic profile of benign, borderline and invasive mucinous ovarian tumours demonstrate a link between borderline and invasive tumours. Exploratory analysis of the genes that are differentially expressed provides some information on the potential genetic events involved in progression from the benign to the malignant phenotype.There is a paucity of clinically reliable information to allow true evidenced-based decision making for the mucinous sub-type. There appears to be a real difference in outcome for patients with advanced mucinous ovarian cancer and a relative resistance to platinum-based chemotherapy is well recognised. Separate trials need to be performed, ideally incor- porating translational research to further elucidate the mechanisms underlying drug resistance, molecular characteristics and potential targets for future therapy.     

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.