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.     

Recurrence of borderline papillary serous tumors: a modern dilemma

Background When defining tumors originating from the epithelial surface of the ovary, a distinction between benign and malignant is made based on clinical and pathologic features. This distinction allows clinicians to make difficult decisions as to which treatment will allow the best possible prognosis for patients with aggressive lesions, while avoiding unnecessary operations for those who are not likely to benefit from surgery. Case We would like to present a patient who was found in the operating room setting to have an extensive recurrence of papillary serous tumor of the ovary. Her original operative diagnosis was that of stage IC papillary serous ovarian carcinoma. The tumor re-occurred as a ventral hernia and during abdominal exploration she was found to have extensive disease. Conclusions Although the survivability of borderline ovarian tumors has been well documented, their recurrence and sites of involvement are not easily defined. Additional studies are needed to further categorize serous borderline tumors and to treat them appropriately.     

Results of cytoreductive surgery for advanced and recurrent ovarian neoplasms and papillary serous carcinomas of the peritoneum

The aim of our study was to review and show the long-term results of the cytoreductive surgery in the treatment of advanced primary and recurrent epithelial ovarian cancers and papillary serous carcinomas of the peritoneum. We wanted to find clinical factors and in this way to select patients who can benefit from this kind of treatment. The clinical data of 32 patients searched retrospectively are presented in our research work. In 29 patients was possible radical cytoreductive surgery. Neoadjuvant and early postoperative chemotherapy were applied in most of the patients. The median follow up after cytoreductive surgery was 50 months. The overall median survival after cytoreduction was 38.5 months. We consider the cytoreductive surgery to be effective only when combined with neoadjuvant or with early postoperative chemotherapy. The surgical approach without chemotherapy leads to bad results.     

Immunohistochemical comparison of primary peritoneal and primary ovarian serous papillary carcinoma.

Twenty-six patients, meeting strict criteria for primary peritoneal serous papillary carcinoma (PPSPC), were matched to 22 patients with ovarian serous papillary cancer (OSPC) for age and stage. Immunohistochemistry was used to determine the status of estrogen receptors (ER), progesterone receptors (PR), the expression of cell proliferation marker Ki-67, and the overexpression of HER-2/neu and p53 protein. Of the PPSPCs, 53.8% were poorly differentiated, as were 18.2% of the OSPCs (p = 0.012). Positive immunostaining for ER and PR was less in PPSPCs (30.8% and 46.2%, respectively) than OSPCs (72.7% and 90.9%; p = 0.003 and p = 0.001, respectively). Conversely, a significant increase in the expression of Ki-67 was found in PPSPCs (37.7%) versus OSPCs (26.8%) (p = 0.039). The same trend was found for HER-2/neu, being overexpressed in 38.5% of the PPSPC versus 9.1% of the OSPCs (p = 0.019). Overexpression of p53 was found in 30.8% of the PPSPCs and 45.4% of the OSPCs (not significant). There was a significantly worse survival rate for PPSPCs than for OSPCs (p = 0.017), yet none of the studied parameters were significantly correlated with survival within the PPSPC and OSPC groups. The significantly different immunohistochemical expression of ER, PR, Ki-67, and HER-2 in PPSPCs compared with OSPCs suggests that different molecular events may lead to tumorigenesis in these two cancers.     

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.     

Allelotype of papillary serous peritoneal carcinomas.

OBJECTIVE: Papillary serous peritoneal carcinoma (PSPC) is histologically indistinguishable from papillary serous ovarian carcinoma (PSOC) with a similar clinical presentation, yet may differ in its carcinogenesis. The purpose of this study was to determine the incidence of allelic loss and the frequency of p53 mutation by p53 overexpression in PSPC compared to PSOC. METHODS: An allelotype analysis of 26 patients with PSPC was performed using 39 microsatellite markers from 25 chromosomal arms. Thirty-seven previously studied patients with PSOC served as the comparison. P53 mutations were detected by immunohistochemical protein overexpression. RESULTS: There was significantly less LOH in PSPC than PSOC. Both the number of chromosomes with LOH and the proportion of tumors with allelic loss were less frequent. Significant LOH, defined as >/=30% of informative tumors having loss at a chromosome locus, was seen on 4 chromosome arms in PSPC: 12p, 17p, 17q, and 18q, compared to 18 arms in PSOC: 4q, 5q, 6p, 6q, 9p, 9q, 12p, 12q, 13q, 15q, 16q, 17p, 17q, 18q, 19p, 19q, 22q, and Xq (P < 0.001). The median LOH frequency was higher in PSOC than PSPC, 43% versus 33%, respectively (P = 0.013), and more PSOC tumors had LOH than PSPC tumors, 91% versus 65% (P = 0.042). P53 overexpression was detected in 80% of PSPC tumors. CONCLUSIONS: LOH occurs less frequently in PSPC compared to PSOC. Chromosomal regions with high frequencies of LOH common to PSPC and PSOC, such as 12p, 17p, 17q, and 18q, may harbor tumor suppressor genes important in the carcinogenesis of both malignancies and likely include p53.     

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.     

卵巢交界性上皮性肿瘤的临床病理分析

目的　探讨影响卵巢交界性上皮性肿瘤预后的临床及病理因素。方法　回顾性分析我院 1973年 1月～ 2 0 0 0年 12月收治的 3 4例卵巢交界性上皮性肿瘤及 3 0例Ⅰ期卵巢上皮性癌 (卵巢癌 )患者的临床病理资料 ,并按 1999年WHO的组织学标准核对诊断。结果　 64例患者中 ,符合卵巢交界性上皮性肿瘤诊断者 3 7例 ,其中 6例微浸润的卵巢交界性上皮性肿瘤曾被误诊为Ⅰ期卵巢癌 ,1例卵巢交界性上皮性肿瘤为非浸润性腹膜种植。卵巢癌组织学类型以黏液性和浆液性为主 ,95 %为国际妇产科联盟 (FIGO)临床分期的Ⅰ期。患者均行手术治疗 ,其中 11例行保守手术者复发率为9% ;2 6例肿瘤细胞减灭术后给予环磷酰胺 +阿霉素 +顺铂 (CAP)方案为主的化学药物治疗 (化疗 )。已随访 5年、10年患者的生存率均达 10 0 %。经多因素相关分析显示 ,组织学类型和是否化疗是影响预后的因素 (P <0 0 1)。结论　卵巢交界性上皮性肿瘤患者以手术治疗为主 ,应适当辅以化疗     

An in vitro study of ovarian atypical proliferating (borderline) serous tumors

Seven human serous ovarian atypically proliferating tumors (tumors of borderline malignancy) were grown in primary culture and compared morphologically with established cell lines derived from serous carcinomas (stage III–IV). Several parameters were investigated in order to establish the place of these tumors in a neoplastic spectrum between benign and frankly malignant serous neoplasms. The atypically proliferating tumors showed serous features, including prominent microvilli and multiple cilia, similar to those found in the malignant serous cells. DNA flow cytometric studies of the atypically proliferating tumors showed them to be diploid. Keratins were strongly expressed immunohistochemically by all the atypically proliferating tumors. Vimentin was also detected in six of the original tumors but only in one primary culture. The capacity to culture and study cells which represent possible intermediate stages in the evolution of ovarian malignancy may prove useful as an in vitro model for this disease.     

Immunohistochemical differentiation between ovarian granulosa cell tumors and ovarian carcinomas

Summary Differential diagnosis is a major problem in histopathology of ovarian tumors. Difficulties may arise if the tumor is a poorly differentiated carcinoma or a granulosa cell tumor of the sarcomatoid type. It was the aim of the present study to evaluate the usefulness of immunohistochemistry in differentiating between granulosa cell tumors of the ovary and ovarian carcinomas. We investigated 56 ovarian malignancies (13 granulosa cell tumors, 17 serous, 14 mucinous and 12 poorly differentiated carcinomas) and performed immunohistochemical detection of Vimentin, Keratin, CA125, CA19-9, CEA, S100 and Ber-EP4. Expression of Vimentin was highest and expression of Keratin was lowest in granulosa cell tumors in contrast to carcinomas. CA125 and CA19-9 were not expressed in granulosa cell tumors, whereas the detection rate in carcinomas (except for CA125 in mucinous carcinomas) was high. CEA, S100 and Ber-EP4 do not seem to be useful markers in differential diagnosis. A marker profile of Vimentin, Keratin, CA125 and CA19-9 allows a quite strict differentiation between poorly differentiated ovarian carcinomas and granulosa cell tumors of the ovary.     

Serous borderline ovarian tumors

Proliferating papillary serous cystadenomas that seldom occur are classified into the group of ovarian tumours of low malignant potential (borderline tumours). The present study includes 33 cases observed in our clinic since 1955. Even though the five-year survival rate being 88% was substantially higher than that for ovarian carcinomas, the prognosis of individual cases cannot be reliably predicted because of the uncertainty as to the biological behaviour in both clinical and histological terms. Consequently, the trend to predominantly radical surgery appears to be a justified approach. Whenever it is desirable to maintain fertility in younger women, conservative surgery would require a unilateral tumour without a ruptured capsule and normal histological findings to be obtained from wedge excision in the opposite ovary.     

Genetic alterations in ovarian borderline tumours and ovarian carcinomas

OBJECTIVE: To evaluate the benefits associated with routine uterine curettage following complete second trimester termination of pregnancy by extraovular prostaglandin E2. STUDY DESIGN: Fifty-five patients between 15 and 24 weeks' gestation who had undergone complete termination of pregnancy by continuous extraovular instillation of prostaglandin E2 (PGE2), were randomly assigned into either no further intervention (n=25), or uterine curettage under general anesthesia (n=30). The need for late uterine curettage, clinical and ultrasonographic parameters at 1 and 42 days follow-up, as well as the incidence of the minor and major complications, were compared between groups. RESULTS: Baseline and post-abortion clinical and ultrasonographic characteristics were similar in both groups. Mean (+/- Standard error of the mean) number of post-abortion bleeding days in the curettage group was 8.9+/-1.8 versus 10.1+/-2.6 days in the non-curettage group (P=NS). No patient in the former group, compared to three patients in the latter group, needed late uterine curettage, (P=NS). Major and minor complications rates in the curettage and in the no-curettage groups were not significantly different. Considerably more patients in the curettage group needed analgesic agents following the abortion compared to the no-curettage group (60% vs. 3.3%, respectively; P<0.001). CONCLUSIONS: Routine uterine curettage in patients undergoing complete second trimester termination of pregnancy by extraovular instillation of PGE2, exerts no benefit.