Risk factors for benign serous and mucinous epithelial ovarian tumors

OBJECTIVE: To investigate the risk factors for benign serous and mucinous epithelial ovarian tumors. METHODS: Cases were women newly diagnosed with benign serous ovarian tumors (n=230) or benign mucinous tumors (n=133) between 2002 and 2005. Control women were selected at random from the general population (n=752). All participants completed a comprehensive reproductive and lifestyle questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and to simultaneously adjust for potential confounding factors. RESULTS: Current smoking was associated with a three-fold increase in risk of benign mucinous tumors (OR 3.25, 95% CI 1.97-5.34), and there was a trend of increasing risk with increasing amount smoked (P<.001). Both recent obesity (OR 1.93, 95% CI 1.30-2.88) and obesity at age 20 (OR 4.38, 95% CI 1.88-10.20) were associated with increased risk of benign serous ovarian tumors, and having had a hysterectomy was also related to increased risk of serous (OR 2.75, 95% CI 1.90-3.96), but not mucinous tumors. Ever having had a term pregnancy was inversely associated with both tumor types (combined OR 0.65, 95% CI 0.43-0.97), although greater numbers of pregnancies did not decrease risk further. Use of hormonal contraceptives was unrelated to risk. CONCLUSION: Our results suggest some differences in risk factors between benign serous and mucinous epithelial ovarian tumors and that risk factors for benign serous tumors differ from those well established for ovarian cancer. The results also suggest that there is potential for prevention of these common conditions through avoidance of smoking and obesity. LEVEL OF EVIDENCE: II.     

Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas.

The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.     

Adjuvant platinum-based chemotherapy for borderline serous ovarian tumors with invasive implants

Background

Most borderline ovarian tumors (BOTs) are cured with surgery. However BOTs with invasive implants have a poor prognosis with a mortality of 20–40%. The benefit of adjuvant chemotherapy (CT) in this setting remains poorly defined.

Methods

Retrospective study of serous BOT + invasive implants treated with adjuvant CT.

Results

36 patients were referred with serous BOTs + invasive implants and treated with surgery and platinum-based CT between 06/1982 and 02/2011. 83% were stage III/IV. Tumors demonstrated microinvasion, micropapillary pattern or desmoplastic implants in 53%, 47% and 67% of cases, respectively. 8% had fertility-sparing surgery. Taking into account initial and completion surgeries, R0 was achieved in 84% (27/32) (NA, N = 4). The majority (72%) received a combination of platinum + taxane. 11% of patients experienced a G3/G4 toxicity. 13 of 36 (36%) patients relapsed at a median of 27.3 months after diagnosis of invasive implants. Among 12 patients with histologically confirmed relapse, 8 patients progressed with invasive disease in the form of carcinoma or invasive implants. 5 year PFS/OS were 67%/96%. Neither microinvasion, micropapillary pattern, nor desmoplastic implants predicted relapse. In cases with evaluable disease, an objective response to chemotherapy was observed in 4 of 6 patients.

Conclusion

This is the largest study of BOT with invasive implants treated with surgery and adjuvant platinum-based CT. Treatment was well tolerated and the invasive relapse rate was 22% (8/36). Although numbers are small, the objective responses suggest a possible role for adjuvant CT in BOTs with invasive implants.     

卵巢交界性黏液性肿瘤130例临床病理分析

目的 探讨卵巢交界性黏液性肿瘤的临床病理特征及复发相关危险因素.方法 选择1994年1月至2008年12月北京协和医院收治的卵巢黏液性交界性肿瘤患者130例,回顾性分析其临床病理特征,包括年龄、术前血清肿瘤标志物(术前有血清CA125、CA199检测资料的患者分别为96、26例)、手术方式、病理特点、手术病理分期及复发情况,并对复发相关因素进行分析.结果 患者平均发病年龄为41岁(14～85岁),分别有34%(33/96)和50%(13/26)的患者术前血清CA125或CA199水平升高.手术方式:广泛性手术(即不保留生育功能的手术)52例(40.0%),保守性手术(即保留生育功能的手术)78例(60.0%),其中54例(41.5%)行单侧附件切除术、24例(18.5%)行患侧肿瘤剔除术;共55例患者进行了全面分期手术,其中保守性手术和广泛性手术分别为27和28例.病理特点:肿瘤平均直径(16±10)cm(4～50 cm),117例(90.0%)患者的肿瘤位于单侧;45例(34.6%)伴良性黏液性肿瘤,14例(10.8%)伴上皮内癌,8例(6.2%)伴间质微浸润癌,4例(3.1%)伴腹膜假黏液瘤.手术病理分期:Ⅰa期59例(45.4%),Ⅰc期62例(47.7%),Ⅱ期2例(1.5%),Ⅲ期7例(5.4%).复发情况:平均随访56.3个月(6～198个月),16例(12.3%)复发,手术至初次复发平均间隔时间为25.6个月(6～62个月),2例为肿瘤相关性死亡.复发相关因素:广泛性手术及保守性手术包括患侧附件切除、患侧卵巢肿瘤剔除术后的复发率分别为4%(2/49)、13%(7/54)和17%(4/24),广泛性手术后的复发率明显低于保守性手术(P＜0.05);Ⅰa、Ⅰc和Ⅲ期患者的复发率分别为3%(2/59)、18%(11/62)和3/7,Ⅰc和Ⅲ期患者的复发率均明显高于Ⅰa期(P＜0.05);伴腹膜黏液瘤患者的复发率为3/4,明显高于其他交界性肿瘤(P＜0.01),而是否伴上皮内癌、间质微浸润癌及行全面分期手术均与复发无关(P＞0.05).结论 卵巢黏液性交界性肿瘤可能为卵巢黏液性癌的癌前病变,但发病年龄轻、期别早、预后好.保守性手术较广泛性手术易复发,但并不影响远期生存;是否伴上皮内癌、间质微浸润癌及行全面分期手术与复发无关;而期别晚、合并腹膜假黏液瘤与复发相关.

Abstract：

Objective To determine the clinicopathologic characteristics of mucinous borderline ovarian tumors (MBOT) and evaluate the risk factors for recurrence. Methods A retrospective study included age, the level of Preoperative serum CA125, surgical procedures, surgical-staging and the risk factors for recurrence in 130 patients with MBOT who were treated from Jan. 1994 to Dec. 2008 in Peking Union Medical College Hospital was done. Results Preoperative serum CA125 and CA199 were elevated in 34% (33/96) and 50% (13/26) of patients respectively. Fifty-two radical surgeries included total hysterectomy and bilateral saipingo-oovarectomy (THBSO) and 78 fertility-sparing surgeries included 54salpingo-oovarectomies (SO) and 24 cystectomy were done. Fifty-five cases underwent comprehensive surgical staging. Mean size of the tumors was (16 ± 10)cm and 90. 0% (117/130) were limited to unilateral ovary. There were 59 (45.4%) cases, 62 (47.7%o) cases, 2 (1.5%) cases and 7 (5.4%) cases in stage Ⅰa, Ⅰc, Ⅱ , Ⅲ , respectively. Forty-five(34.6%)concurrent with benign mucinous tumors, 14(10.8%)ovarian intraepithelial carcinoma, 8 (6.2%) micro-invasive carcinoma and 4 (3.1%) pseudomyxoma peritonei were found. Median duration for follow-up was 56.3 months. Sixteen (12.3%) recurrences and 2 tumor related deaths were found. Median duration from surgery to recurrence was 25.6 months. Recurrent rate after THBSO(4%, 2/49)was significantly lower than that of SO(13%, 7/54) and cystectomy (17%,4/24; P ＜ 0.05). The recurrent rate of Ⅰc or Ⅲ was 18% (11/62) or 3/7, which were significantly higher than that of stage Ⅰa (3% ,2/59; P ＜0.05). Three of the 4 pseudomyxoma peritonei appeared recurrence.While,the results showed that these were no effect on recurrent rate whether concurrent intraepithelial,microinvasive carcinoma or not comprehensive staging surgery. Conclusions Majority of MBOT were diagnosed in early stage and have favorable prognosis. Patients who take conservative surgery had higher recurrence rate than those radical surgery, but it doesn't affect survival. Late stage and concurrent pseudomyxoma peritonei are risk factors for recurrence.     

Nuclear deoxyribonucleic acid heterogeneity of ovarian borderline malignant serous tumors

Sixteen borderline malignant serous ovarian tumors and seven well-differentiated invasive serous ovarian carcinomas were examined with the technique of Feulgen microspectrophotometry for the determination of nuclear deoxyribonucleic acid (DNA) ploidy patterns (diploid versus aneuploid) and ploidy levels of the stem cell lines. Of the nine stage I-II borderline malignant tumors, only one (11%) was aneuploid. In contrast, four of seven (57%) stage III borderline malignant neoplasms and all stage III carcinomas were aneuploid. The stem cell modal values in all borderline serous tumors were less than triploid (3N) while in five of seven carcinomas stem cell modal values were greater than triploidy. This contrast in ploidy patterns and ploidy levels may explain the differences in biologic behavior between borderline malignant serous tumors and invasive serous carcinomas of the ovary.     

Cytoplasmic CD24 expression in advanced ovarian serous borderline tumors

OBJECTIVES: CD24, originally described as a B-cell marker, has been revealed as one of the candidate molecular markers of epithelial ovarian cancer. We aimed to determine the pattern and extent of CD24 expression in ovarian serous tumors and to clarify its relationship with pathological parameters, especially those associated with the early events of tumor progression in serous tumors of borderline malignancy. METHODS: A total of 114 ovarian serous tumors, including 9 adenomas, 34 borderline, and 71 carcinomas, were analyzed immunohistochemically using a CD24 monoclonal antibody on paraffin blocks. RESULTS: In normal epithelium and serous cystadenomas, the CD24 expression was localized to the apical membranous portion. In some of borderline tumors (26.4%), additional cytoplasmic expression was observed. The cytoplasmic expression of CD24 in borderline tumors was associated with microinvasion (P = 0.001) and omental implants (P = 0.033) with statistical significance. Serous adenocarcinomas showed strong diffuse cytoplasmic expression of CD24, which was significantly associated with shortened survival rate both in univariate (P = 0.011) and multivariate (P = 0.009) analysis. CONCLUSION: The loss of apical localization with the acquisition of the cytoplasmic staining of CD24 protein is a surrogate marker of stromal invasion in ovarian serous tumors of borderline malignancy. Furthermore, the increase in the cytoplasmic expression of CD24 protein is a strong independent molecular marker for shortened survival rate of patients with ovarian serous adenocarcinomas.     

Conservative treatment of patients with borderline ovarian tumors

OBJECTIVES: The aim of this study was to characterise group of patients with borderline tumours undergoing surgical treatment. DESIGN: The analysis included 83 patients with ovarian tumours of borderline malignancy at stage Ia, operated in the Gynaecological Department of Medical University of Gdańsk between 1978-1997. The study takes into account comparison of: age of patients, type of surgery, tumour pathology, post surgical treatment. Furthermore, long term follow up was assessed. RESULTS: In the group of 83 patients with stage Ia 37 ware treated with conservative surgery, 46 underwent radical treatment. Postsurgical chemical treatment was not applied. Three patients had to be reoperated because of neoplasm disease recurrence. 8 patients were died from reasons not connected with main disease. CONCLUSIONS: Conservative surgery is proper treatment for young women with borderline ovary tumours in stage Ia. For older, perimenopausal women TAH with BSO without additional chemotherapy is suggested.     

Extraovarian mucinous metaplasia in a patient with bilateral mucinous borderline ovarian tumors: a case report.

We present a case of a 54-year-old woman with bilateral borderline mucinous ovarian tumors that contained multiple types of epithelia. Widespread müllerian abnormalities were present and included endometrial mucinous metaplasia, mucinous epithelial inclusions with papillary changes in pelvic lymph nodes, and papillary mucinous proliferation within endocervical glands. We postulate that the widespread abnormalities present in this patient could represent precursor changes to the multifocal cancers previously described in patients with similar tumors.     

Broad ligament mucinous and serous cystadenomas of borderline malignancy

The clinical and pathological findings including light microscopic and ultrastructural features of two cases of borderline mucinous and serous cystadenomas that originated in the broad ligament are reported. The tumors did not involve the oviduct or ovary. They probably arose in pre-existing cysts of mesothelial and paramesonephric (primary Müllerian) origin. These rare tumors bear a close resemblance to the borderline epithelial tumors of the ovary and the same prognostic criteria may be applicable to the lesions presented here.     

Biochemical and immunohistochemical studies on carcinoembryonic antigen of ovarian mucinous and serous tumors

The carcinoembryonic antigen (CEA) in the cyst fluid of ovarian mucinous and serous tumors was investigated. The molecular weight and antigenicity of the CEA from both ovarian tumors were very similar to those of colon cancer CEA as determined by SDS electrophoresis and double immunodiffusion on agar plates. In the cyst fluid of ovarian mucinous tumors, the amount of CEA was generally high and CEA of molecular weight (MW) 200,000 was increased. In contrast, in the cyst fluid of ovarian serous tumors, the CEA amount was low and CEA variants of MW 370,000 and 180,000 were present in addition to the main CEA of MW 200,000. Immunohistochemically, CEA was stained mainly in the intestinal type epithelium of ovarian mucinous tumors, and the CEA revealed a tendency to be stained more frequently and strongly with increasing degree of tumor malignancy. Thus, ovarian mucinous tumors (especially the intestinal type epithelium) produced large amounts of CEA which closely resembled colon cancer CEA, whereas ovarian serous tumors produced small amounts of CEA, including some CEA variants. In the study of ovarian epithelial tumors, CEA may be useful as a marker for the malignant transformation of ovarian mucinous tumors.     

Mucosubstances in classification of serous and mucinous ovarian tumors: a morphometrical study

108 serous and 106 mucinous ovarian cystadenomas of varying malignancy were studied with the saliva-periodic acid-Schiff (SPAS) reaction and with the Alcian blue (AB) pH 2.7 method, which stain neutral and acid mucosubstances, respectively. Positively stained mucin was quantitated morphometrically and the measured parameters were tested by discriminant analysis. As expected, the mucinous tumors were more positive for mucin than the serous ones. Also the borderline tumors contained more mucin than their benign or malignant counterparts. The best discriminating capacity for mucin was obtained in serous tumors with the AB stain and in mucinous tumors with the SPAS reaction. The ratio of neutral to acid mucosubstances decreased in mucinous cystadenomas with increasing malignancy.     

Periodic acid-Schiff stain as a prognostic indicator in serous and mucinous ovarian tumors

The prognostic significance of periodic acid-Schiff (PAS) stain in 112 serous: 43 benign, 25 borderline and 44 malignant cystadenomas: and in 106 mucinous: 60 benign, 32 borderline and 14 malignant cystadenomas of the ovary were investigated. The amount of positively stained mucin was estimated morphometrically. The outcome of most patients with benign or borderline lesion was good. One patient with benign mucinous cystadenoma died, however, of pseudomyxoma peritonei and another patient with borderline mucinous cystadenoma died of peritoneal carcinosis. Other patients were alive and free of the disease after a follow-up of 1-14 years, or had died of causes unrelated to the ovarian disease. Abundant PAS positive mucin predicted a longer survival both in serous and in mucinous malignant tumors. The 5-year survivals for the serous cystadenocarcinomas with and without PAS positive mucin were 21% and 13%, respectively (not statistically significant). For mucinous cystadenocarcinomas with mucin value over and below the median, the 5-year survival rates were 57% and 14%, respectively (P less than 0.10). High PAS positivity in both serous and mucinous cystadenocarcinomas clearly indicated better prognosis, although statistical significance was not achieved. Thus, further studies are needed for final evaluation of the prognostic significance of the PAS stain in these ovarian tumors.