Comparison of the clinical behavior of newly diagnosed stages II-IV low-grade serous carcinoma of the ovary with that of serous ovarian tumors of low malignant potential that recur as low-grade serous carcinoma

BACKGROUND: Serous ovarian tumors of low malignant potential (STLMP) frequently coexist with low-grade serous carcinoma of the ovary (LGSC) and, when they recur, frequently do so as LGSC. The purpose of this study was to compare the outcomes of patients with these two tumor types. METHODS: All patients with stages II-IV LGSC (group 1) or with STLMP that recurred as LGSC (group 2) seen at our institution from 1973 to 2003 were identified, and demographic data were obtained. For group 1, progression-free and overall survival times were calculated from the date of primary diagnosis to the date of disease progression/recurrence or the date of last contact/death, respectively. For group 2, progression-free and overall survival times were calculated from the date of first relapse as a LGSC to the date of progression or the date of last contact/death, respectively. The method of Kaplan and Meier was used to estimate survival, and the log-rank test was used to compare differences between survival curves. RESULTS: We identified 112 patients in group 1 and 41 in group 2. There were no statistically significant differences between the two groups in median age (42.7 vs. 45.4 years [at relapse]; P=0.37), progression-free survival time (19.5 vs. 25 months; P=0.92), or overall survival time (81.8 vs. 82.8 months; P=0.84). CONCLUSIONS: The age at diagnosis, progression-free survival time, and overall survival time associated with newly diagnosed stages II-IV LGSC of the ovary are similar to those of STLMP that recur as LGSC, providing further evidence of an association between these two tumor types.     

Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum

Objective

To determine whether hormonal therapies have efficacy in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum.

Methods

We searched departmental databases for patients with histologically-confirmed, evaluable, recurrent low-grade serous ovarian or peritoneal carcinoma who received hormonal therapy at our institution between 1989 and 2009. We retrospectively reviewed patients' medical records for demographic, disease, hormonal therapy, and estrogen receptor and progesterone receptor expression data. We used the Response Evaluation Criteria in Solid Tumors version 1.1 to determine patients' responses to hormonal therapy. Because patients could have received more than one evaluable hormonal therapy regimen, we chose to define the outcome metric as “patient-regimens.” Median time to disease progression (TTP) and overall survival (OS) were also calculated. Regression analysis was also performed.

Results

We identified 64 patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Patients' median TTP and median OS were 7.4 and 78.2 months, respectively. Patients received 89 separate hormonal patient-regimens, which produced an overall response rate of 9% (6 complete responses and 2 partial responses). Sixty-one percent of the patient-regimens resulted in a progression-free survival duration of at least 6 months. Patient-regimens involving ER +/PR + disease produced a longer median TTP (8.9 months) than patient-regimens involving ER +/PR − disease did (6.2 months; p = 0.053). This difference approached but did not reach statistical significance.

Conclusions

Hormonal therapies have moderate anti-tumor activity in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Further study to determine whether ER/PR expression status is a predictive biomarker for this rare cancer subtype is warranted.     

Utility of F-FDG PET/CT in follow-up of patients with low-grade serous carcinoma of the ovary

Objective

Ovarian low-grade serous carcinoma (LGSC) is a rare and indolent tumor. The utility of ¹⁸F-FDG PET/CT in monitoring patients with LGSC has not been established. We assessed the accuracy and clinical impact of ¹⁸F-FDG PET/CT in patients with ovarian LGSC after initial treatment.

Methods

A retrospective analysis was performed on patients with ovarian LGSC who had undergone ¹⁸F-FDG PET/CT scans during follow-up after primary treatment. The impact of ¹⁸F-FDG PET/CT on the management plan was assessed. The sensitivity, specificity, and accuracy of ¹⁸F-FDG PET/CT findings in the detection of recurrence were calculated. Total lesion glycolysis (TLG) was determined to assess metabolic activity of tumors. Potential prognostic factors for disease-free and overall survival after recurrence were assessed.

Results

Forty-eight patients were included in the analysis, 39 with recurrent disease and 9 without recurrence. A total of 91 ¹⁸F-FDG PET/CT scans were performed, and 30% of these (27/91) had an impact on the management plan. Sensitivity, specificity, and accuracy in the detection of LGSC recurrence were 94%, 100%, and 97%, respectively, for ¹⁸F-FDG PET/CT; 89%, 95%, and 93%,respectively, for CT; and 68%, 89%, and 73%, respectively, for serum CA-125. There was no significant difference in sensitivity between PET/CT and CT. Survival after recurrence was poorer in patients with a TLG value greater than 67.7 g.

Conclusions

¹⁸F-FDG PET/CT may provide useful information during the follow-up of patients with LGSC after initial treatment. TLG may be a predictor of survival after recurrence.     

Ovarian low-grade serous carcinoma: a comprehensive update

Ovarian low-grade serous ovarian carcinoma (OvLGSCa) comprises a minority within the heterogeneous group of ovarian carcinomas. Despite biological differences with their high-grade serous counterparts, current treatment guidelines do not distinguish between these two entities. OvLGSCas are characterized by an indolent clinical course. They usually develop from serous tumors of low malignant potential, although they can also arise de novo. When compared with patients with ovarian high grade serous carcinoma (OvHGSCa) patients with OvLGSCa are younger and have better survival outcomes. Current clinical and treatment data available for OvLGSCa come from retrospective studies, suggesting that optimal cytoreductive surgery remains the cornerstone in treatment, whereas chemotherapy has a limited role. Molecular studies have revealed the preponderance of the RAS-RAF-MAPK signaling pathway in the pathogenesis of OvLGSCa, thereby representing an attractive therapeutic target for patients affected by this disease. Improved clinical trial designs and international collaboration are required to optimally address the unmet medical treatment needs of patients affected by this disease.     

Papillary serous carcinoma of the ovary with squamous differentiation

Two cases of serous carcinoma of the ovary with squamous differentiation are described. These neoplasms occurred in two women who were 63 and 46 years old and who presented with International Federation of Gynecology and Obstetrics (FIGO) stage IIB and III disease, respectively. The first tumor recurred following chemotherapy; radiotherapy was given, but the patient died of tumor at 4 years. The second neoplasm did not respond to chemotherapy and caused the patient's death at 2 years. In the first case, the squamous differentiation occurred as compact nests of ovoid to spindle cells intermixed with a papillary serous carcinoma component. The squamous component of the second case developed as single or small groups of enlarged, eosinophilic cells, often multinucleated, within nests of papillary serous carcinoma with typical psammoma bodies. In the latter case, intercellular bridges were identified by light microscopy. Both cases showed squamous features by immunohistochemistry, staining positively for 57-kd keratin, although in the first case but not the second there was also some weaker staining for 54-kd keratin, probably indicating incomplete squamous differentiation with retained glandular features. Electron microscopy in both cases revealed prominent cytoplasmic tonofilaments in the squamous component. These two cases reinforce the concept that squamous differentiation, although more frequent in some other types of common epithelial tumors, may occur in serous ovarian carcinomas as well.     

Testing of two binary grading systems for FIGO stage III serous carcinoma of the ovary and peritoneum

OBJECTIVE: A variety of histologic grading systems for ovarian carcinoma have been used, but there is no widely accepted system. Binary grading systems are inherently superior to the more common three-grade systems because they are more reproducible and they correspond to the number of options in the binary treatment decision for which grade is considered important: the use of or withholding of chemotherapy. METHODS: One hundred thirteen unselected FIGO stage III serous carcinomas of the ovary and peritoneum were tested with two grading systems: a binary system recently proposed by investigators at MD Anderson Cancer Center (MDACC) and a new binary system we formulated at the Washington Hospital Center (WHC). Both of these systems are based on nuclear grade. The WHC system has a higher threshold of nuclear size for diagnosing high-grade tumors. RESULTS: The WHC system separated the cases into 89 high-grade and 24 low-grade tumors. The median survival rates were 30 and 49 months for high and low grade respectively, and the actuarial survival curves were not significantly different (P > 0.10). The MDACC system separated the cases into 103 high-grade and 10 low-grade tumors. With this system, low-grade tumors were significantly more likely than high grade to be stage IIIA (P < 0.05) and occurred at a mean age of 57 years compared to 65 years for high-grade tumors (P < 0.05). Low-grade tumors were suboptimally debulked in 10% of cases compared to 27% for high-grade tumors (P > 0.05). The median survival for high-grade tumors was 34 months, and the median for low grade has not been reached. The actuarial survival curves were not significantly different (P = 0.065). CONCLUSION: The MDACC grading system appears more promising than the WHC system. The MDACC system separates a small (9% of advanced stage serous carcinomas) but distinctive well-differentiated tumor which usually has the appearance of invasive low-grade (micropapillary) serous carcinoma. The rarity of this tumor, however, will require a larger series to demonstrate prognostic value. The WHC system, which was designed to enlarge the low-grade group to a size that would be more meaningful in clinical practice, did not demonstrate a survival difference. The failure of the WHC system suggests that attempts to enlarge the low-grade group using histologic features alone are unlikely to be successful. The potential for confounding of grade with substage, volume of residual disease and patient age are issues that may impede determination of the independence of tumor grade in prognosis, and more data, especially for low-grade tumors, are needed.     

Differences of chemoresistance assay between invasive micropapillary/low-grade serous ovarian carcinoma and high-grade serous ovarian carcinoma

The objective of this study was to evaluate the pattern of chemoresistance in invasive micropapillary/low-grade serous ovarian carcinoma (invasive MPSC/LGSC) and high-grade serous ovarian carcinoma (HGSC) according to extreme drug resistance (EDR) assay testing. Surgical specimens of 44 recurrent ovarian cancer patients harvested at the time of cytoreductive surgery between August 1999 and February 2004 were identified retrospectively from the tumor registry database. Thirteen patients (29.5%) had recurrent invasive MPSC/LGSC and 31 (70.5%) patients had recurrent HGSC. Eight drugs were evaluated; EDR assay results were compared between LGSC and HGSC groups using Fisher exact tests and exact logistic regression models. Compared to HGSC, invasive MPSC/LGSC were more likely to manifest EDR to the drugs paclitaxel (69% vs 14%, P < 0.001), carboplatin (50% vs 17%, P= 0.05), cyclophosphamide (40% vs 23%, P= 0.41), gemcitabine (36% vs 19%, P= 0.40), and cisplatin (33% vs 28%, P= 0.72) and less likely to be resistant to etoposide (0% vs 44%, P= 0.007), doxorubicin (8% vs 45%, P= 0.03), and topotecan (8% vs 21%, P= 0.65). Exact logistic regression estimates revealed that invasive MPSC/LGSC patients had significantly increased probabilities of paclitaxel resistance odds ratio (OR) = 12.5 (95% CI: 2.3-100.0), P= 0.001 and carboplatin resistance OR = 4.8 (95% CI: 0.9-25.0), P= 0.07, while the HGSC cases were more likely to be resistant to etoposide OR = 12.1 (95% CI: 1.7-infinity), P=0.009 and doxorubicin OR = 8.6 (95% CI: 1.0-413.7), P= 0.05. In this retrospective analysis, patients with recurrent invasive MPSC/LGSC were more likely to manifest EDR to standard chemotherapy agents (platinum and paclitaxel). These observations may help to guide chemotherapeutic decision making in these patients if confirmed in a large-scale study.     

Quantification of ER/PR expression in ovarian low-grade serous carcinoma

ObjectiveCase reports suggest that hormonal therapy may be a useful treatment option for low-grade serous carcinomas (LGSC) but the clinical value remains uncertain. We hypothesized that LGSCs show a constitutive high hormone receptor expression and that type diagnosis may be sufficient to initiate hormonal therapy.MethodsWe assessed ER and PR expression on 27 LGSC, 69 high-grade serous carcinomas (HGSC), 36 serous borderline tumors (SBOT), and five normal fallopian tubes using three different platforms/antibodies on tissue microarrays. Staining from the Leica Bond Max and DAKO PharmDx platforms was evaluated using the Allred score. Quantitative fluorescence immunohistochemistry was performed using the HistoRx AQUAnalysis platform. A second cohort of 12 LGSC and 183 HGSC was assessed using the HistoRx AQUAnalysis platform. Welch ANOVA or Fisher's Exact Test was used to compare differences in the histological types for each platform. Nonparametric bivariate density plots were used to graphically demonstrate the relationship between ER and PR for the various histological types.ResultsLGSC have higher ER and PR expression compared to HGSC but significantly less than FT and SBOT. Nonparametric bivariate density revealed two populations of LGSC: one fifth of LGSC are ER high/PR high expressers similar to SBOT but the majority show low ER/PR expression more like HGSC.ConclusionsQuantitative assessment of ER/PR expression using the HistoRx AQUAnalysis platform may be useful as a predictive diagnostic for hormonal therapy in LGSC, assuming that only the fraction of double high expressers benefit from hormonal treatment.     

Papillary serous carcinoma of the ovary following prolonged tamoxifen treatment.

We present a patient with breast cancer who developed papillary serous adenocarcinoma of the ovary after 13 years of tamoxifen use. The possible association is explored and the literature is reviewed.     

Bilateral micropapillary serous carcinoma of the ovary: a case report

BACKGROUND: Micropapillary serous carcinoma (MPSC), a recently described entity in the group of serous borderline tumor, needs to be recognized and separated from serous borderline tumor of usual type (SBT) as MPSC has a worse prognosis. CASE REPORT: We report the case of a 21-year-old female with gradually increasing lump abdomen for 6 months. Ultrasonography showed bilateral ovarian enlargement with cysts. Laparotomy revealed both ovaries to be enlarged and right ovary showed capsular breach. With a per-operative diagnosis of bilateral malignant ovarian tumor, total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Multiple sections from both ovaries showed non-invasive micropapillary serous carcinoma with right ovary showing surface growth but no definite capsular breach. The final histological diagnosis was bilateral micropapillary serous carcinoma. The patient has been asymptomatic in 10-month follow-up. CONCLUSION: MPSC, classified as serous borderline tumor, needs to be differentiated from APST as well as conventional serous carcinoma. It is diagnosed according to strict criteria laid down. Multiple sections should be studied to exclude invasion. Adequate peritoneal sampling should be performed to look for implants, which is of prognostic significance.     

Clinical predictors of long-term survival for stage IVB uterine papillary serous carcinoma confined to the abdomen

Objective

To identify clinical predictors of long-term survival in women with FIGO Stage IVB uterine papillary serous carcinoma (UPSC) confined to the abdomen

Methods

Records were reviewed for 48 patients with Stage IVB UPSC diagnosed from 1/1980 to 12/2011. Study inclusion required hysterectomy, salpingo-oophorectomy and negative chest imaging. Disease-free (DFS) and overall (OS) survival rates were calculated using the Kaplan–Meier method. Multivariate analysis (MVA) was performed using Cox proportional hazards.

Results

Median age at diagnosis was 70 years (range, 53–87). Optimal cytoreduction (Opt) to < 1 cm residual disease was performed in 36 patients (75%). With a median follow-up of 21 months for all patients and 99 months for survivors, 36 (75%) experienced disease progression or relapse, most commonly intraperitoneal (16, 44%). At 5 years, DFS and OS rates were 12% and 19%, respectively. Five patients (10%) were long-term survivors without relapse at a median of 124 months. All 5 had Opt and carboplatin/paclitaxel chemotherapy, and 4 received radiotherapy (2 pelvic, 1 whole-abdominal, 1 brachytherapy). On MVA in the chemotherapy-treated population, Opt (HR 0.09, 95% CI 0.02–0.35) and radiotherapy (HR 0.36, 0.15–0.80) were associated with decreased rates of recurrence or progression. Opt (HR 0.09, 0.02–0.38) was prognostic for OS when adjusted for age.

Conclusions

Clinical predictors of long-term survival for Stage IVB UPSC confined to the abdomen include optimal cytoreduction and adjuvant platinum and paclitaxel chemotherapy. Radiotherapy may decrease rates of recurrence or progression. Despite intra-abdominal involvement, disease remission and long-term survival may be achieved in some patients.     

Fertility results after conservative treatment of advanced stage serous borderline tumour of the ovary

Objective To assess the fertility of patients treated conservatively for a Stage II or III borderline ovarian tumour.
Design A retrospective study.
Setting Gynaecological oncology department in a French anti-cancer centre.
Population Seventeen patients treated with conservative management for a Stage II (   n = 6  ) or III (   n = 11  ) borderline ovarian tumour were followed up. Fifteen patients underwent a unilateral salpingo-oophorectomy (with contralateral cystectomy in six patients), one had unilateral cystectomy and one a bilateral cystectomy. Fourteen patients had non-invasive implants and three had invasive implants.
Main outcome measures Pregnancy rates and outcome.
Results Eight pregnancies were observed in seven patients in a median delay of eight months following the surgical procedure. Six pregnancies were observed spontaneously, one occurred after an ovarian stimulation and one after an IVF procedure. None of these patients recurred under the form of invasive ovarian carcinoma on the spared ovary. Two patients (one with a non-invasive disease and one with an invasive one) had recurrence in the form of evolutive invasive implants, but neither woman died.
Conclusion Spontaneous pregnancy can occur after conservative treatment of advanced stage borderline tumour of the ovary (with non-invasive implants). Such management, performed in a close follow up of the patients, does not affect the overall survival. Conservative surgery could be proposed in patients with borderline tumour of the ovary and non-invasive peritoneal implants.     

Prognostic value of measurements of angiogenesis in serous carcinoma of the ovary.

The study objective was to determine whether tumor vascularity correlates with patient survival, to compare newer semiautomated methods of angiogenesis assessment to older methods, and to determine if advanced image analysis methods can offer useful patient outcome data in serous ovarian cancer.Using the specific endothelial marker CD34, microvessel determinations were quantified in 132 serous ovarian tumors by manual counting at final magnifications of x 200 and x 400 in the most highly vascular areas. Computer-assisted image analysis microvessel counts, endothelial area estimates, and minimum spanning tree (MST) analysis of capillary architecture, which involves assessment of intercapillary distances, were correlated with traditional manual techniques.Manual, semiautomated, and advanced image analysis methods were found to be highly reproducible and express strong correlation with one another. Univariate cyclooxygenase analysis revealed angiogenesis parameters to be highly significant predictors for overall survival (OS) and disease-free survival. Multivariate cyclooxygenase analysis revealed maximum MST (P = 0.009), length MST (P = 0.005), 1 nearest neighbor (P 相似文献   

卵巢上皮性包涵体的起源与低级别卵巢浆液性癌的发病机制

目的 探讨卵巢上皮性包涵体的起源与低级别卵巢浆液性癌的发病机制.方法 收集山东大学齐鲁医院和美国亚利桑那大学附属医院病理科自2000年5月至2010年4月间收治的卵巢浆液性肿瘤患者及行预防性附件切除术患者的手术标本共198份.其中,卵巢肿瘤标本138份,包括卵巢浆液性囊腺瘤53份、卵巢交界性浆液性肿瘤44份、低级别卵巢浆液性癌41份;无明显病理学变化的同侧卵巢及输卵管标本116份(卵巢及输卵管分别为60、56份),取自60例行预防性附件切除术患者的一侧附件.HE染色后镜下观察所有标本的病理学形态特点;并采用免疫组化单染色法检测其免疫表型配对盒基因8抗原( PAX8)、钙结合蛋白(calretinin)、微管蛋白(tubulin)、核增殖相关抗原(Ki-67)的表达,免疫组化双染色法检测其免疫表型PAX8/calretinin的表达.结果 免疫组化PAX8、calretinin单染色法检测显示,90％( 54/60)的卵巢表面生发上皮细胞的免疫表型为PAX8阴性(-)、calretinin阳性(+),HE染色后镜下观察符合间皮组织的形态特点,为间皮型上皮;但有10％(6/60)的卵巢表面生发上皮细胞的免疫表型为PAX8(+)、calretinin(-),HE染色后镜下观察其与输卵管上皮组织的形态相似,为输卵管型上皮.60份正常卵巢中共有921个卵巢上皮性包涵体,表现出两种免疫表型,79％( 728/921)为PAX8(+)、calretinin(-),HE染色后镜下观察其与输卵管上皮组织的形态相似,为输卵管型包涵体;21％(193/921)为PAX8(-)、calretinin(+),HE染色后镜下观察其与间皮组织的形态相似,为间皮型包涵体.免疫组化PAX8/calretinin双染色法进一步验证了卵巢上皮性包涵体的这两种免疫表型.免疫组化PAX8、calretinin、tubulin单染色法检测显示,免疫表型为PAX8(+)、calretinin(-)、tubulin(+)的卵巢表面生发上皮和卵巢上皮性包涵体均包含纤毛型细胞和分泌型细胞2种柱状细胞,形态上接近输卵管黏膜上皮;而免疫表型为PAX8(-)、calretinin(+)、tubulin(+)的卵巢表面生发上皮和卵巢上皮性包涵体则为单层扁平或立方形细胞,与间皮组织的细胞形态类似.免疫组化tubulin、Ki-67单染色法检测显示,分泌型细胞与纤毛型细胞数的比值和细胞增殖指数在卵巢上皮性包涵体及卵巢浆液性囊腺瘤、卵巢交界性浆液性肿瘤、低级别卵巢浆液性癌中呈明显递增趋势(P＜0.05).结论 免疫表型为PAX8(+)、calretinin(-)的卵巢上皮性包涵体可能起源于输卵管,低级别卵巢浆液性癌的发生可能与分泌型细胞的克隆扩增有关.     

Outcomes in surgical stage I uterine papillary serous carcinoma

OBJECTIVE: The optimal management of patients with stage I uterine papillary serous carcinoma (UPSC) is unclear. We sought to determine whether outcomes of women with surgical stage I UPSC differ with and without adjuvant therapy. METHODS: Retrospective multi-institution analysis of women with stage I UPSC surgically staged from 1976 to 2006. Inclusion criteria: comprehensive staging procedure including hysterectomy, bilateral salpingo-oophorectomy, selective pelvic/aortic lymphadenectomy, peritoneal cytology. Recurrence and survival were analyzed using Kaplan-Meier method. RESULTS: Of 83 women with stage I UPSC, 36 (43%) received adjuvant therapies (23% radiotherapy, 3% chemotherapy, 15% chemotherapy and radiotherapy, 2% progestins). Three-year overall (OS) and progression-free survival (PFS) were 80% and 68%, respectively. Three-year OS and PFS by adjuvant treatment were observation (N=47) 86% and 78%, radiotherapy (N=17) 63% and 44%, chemotherapy with or without radiotherapy (N=17) 92% and 76%, respectively. Of the 18 recurrences, 9 (50%) included an extrapelvic component. Local recurrence was 2/30 (7%) following adjuvant radiotherapy and 7/53 (13%) without radiotherapy (p=0.48). Recurrence was higher in stage IB/IC (15/51, 29%) compared to stage IA (3/32, 9%). There has been one recurrence (5%) among the 22 women observed with stage IA disease. CONCLUSION: In this largest reported series of women with surgical stage I UPSC, the high recurrence (29%) among patients with stage IB/IC disease highlights the need for clinical trials to test new therapeutic approaches. Surgically staged patients with IA disease had good prognosis. These data suggest that radiotherapy alone is not effective, that systemic therapy is needed, and that observation could be considered in patients with stage IA disease.