{"paper_id":"348ee05d-75a2-4866-85eb-c1dc2e87d037","body_text":"Clin Chem Lab Med 2009;47(5):537–542 /H170502009 by Walter de Gruyter •Berlin •New Y ork. DOI 10.1515/CCLM.2009.134 2009/623\nArticle in press - uncorrected proof\nPredictive value of CA 125 and CA 72-4 in ovarian\nborderline tumors\nMiriam S. Lenhard 1,*, Stefanie Nehring 1,\nDorothea Nagel 2, Doris Mayr 3, Angela\nKirschenhofer1, Linda Hertlein 1, Klaus Friese 1,\nPetra Stieber 2 and Alexander Burges 1\n1 Department of Obstetrics and Gynecology, Ludwig-\nMaximilians-University Munich, Campus\nGroßhadern, Munich, Germany\n2 Department of Clinical Chemistry, Ludwig-\nMaximilians-University Munich, Campus\nGroßhadern, Munich, Germany\n3 Department of Pathology, Ludwig-Maximilians-\nUniversity Munich, Campus Großhadern, Munich,\nGermany\nAbstract\nBackground: The aim of this study was to assess the\nprognostic value of cancer antigen (CA) 125 and CA\n72-4 in patients with ovarian borderline tumor (BOT).\nMethods: All women diagnosed and treated for BOT\nat our institution between 1981 and 2008 were includ-\ned into this retrospective study (n s101). Preopera-\ntively collected serum samples were analyzed for CA\n125 (Architect, Abbott and Elecsys, Roche) and CA 72-\n4 (Elecsys, Roche) with reference to clinical data and\ncompared to healthy women (n s109) and ovarian\ncancer patients (n s130).\nResults: With a median of 34.7 U/mL (range 18.1–\n385.0 U/mL) for CA 125 and 2.3 U/mL (range\n0.2–277.0 U/mL) for CA 72-4, serum tumor markers in\nBOT patients were significantly elevated as compared\nto healthy women with a median CA 125 of 13.5\nU/mL (range 4.0–49.7 U/mL) and median CA 72-4 of\n0.8 U/mL (range 0.2–20.6 U/mL). In addition, there\nwas a significant difference compared with ovarian\ncancer patients who showed a median CA 125 of\n401.5 U/mL (range 12.5–35,813 U/mL), but no differ-\nence was observed for CA 72-4 (median 3.9 U/mL,\nrange 0.3–10,068 U/mL). Patients with a pT1a tumor\nstage had significantly lower values of CA 125 but not\nof CA 72-4 compared with individuals with higher\ntumor stages (median CA 125 29.9 U/mL for pT1a vs.\n50.9 U/mL for )pT1a; p s0.014). There was a trend\nfor increased concentrations of CA 125 but not of CA\n72-4 in the presence of ascites, endometriosis or peri-\ntoneal implants at primary diagnosis. With respect to\nthe prognostic value of CA 125 or CA 72-4, CA 125\n*Corresponding author: Miriam Lenhard, MD, Department\nof Obstetrics and Gynecology, Ludwig-Maximilians-\nUniversity Munich, Campus Großhadern,\nMarchioninistraße 15, 80337 Munich, Germany\nPhone: q49-89-7095-0, Fax: q49-89-7095-6724,\nE-mail: Miriam.Lenhard@med.uni-muenchen.de\nReceived December 18, 2008; accepted March 2, 2009;\npreviously published online March 25, 2009\nwas significantly higher at primary diagnosis in\npatients who later developed recurrence (251.0 U/mL\nvs. 34.65 U/mL, p s0.012).\nConclusions: Serum CA 125 and CA 72-4 concentra-\ntions in BOT patients differ from healthy controls and\npatients with ovarian cancer. CA 125, but not CA 72-\n4, at primary diagnosis correlates with tumor stage\nand tends to be increased in the presence of ascites,\nendometriosis or peritoneal implants. Moreover, CA\n125 at primary diagnosis appears to have prognostic\nvalue for recurrence.\nClin Chem Lab Med 2009;47:537–42.\nKeywords: biomarker; CA 125; CA 72-4; ovarian bor-\nderline tumor (BOT); prognosis; tumor marker.\nIntroduction\nOvarian borderline tumors (BOT) account for\n10%–20% of epithelial ovarian tumors (1). Often\ndescribed as a tumor of low malignant potential, it is\nclassified as a separate entity by the International\nFederation of Gynecology and Obstetrics (2). It has an\nincidence of 4.8/100,000 per year (3), and an excellent\nclinical outcome reflected by 10-year survival rates of\n;90% (4). Recurrence rates according to the literature\nvary between 8% and 32% (5–9). Few studies have\nanalyzed risk factors for disease recurrence or prog-\nnosis (9–11). Since borderline tumors of the ovary\nhave been described as showing late recurrence (12),\nlong-term follow-up is required to assess prognosis.\nThere is little information on the prognostic value\nof preoperative tumor markers in BOT. It is known\nthat preoperative cancer antigen (CA) 125 concentra-\ntions are increased in fewer patients with BOT com-\npared to ovarian cancer (13). In ovarian cancer, the\nmagnitude of increase in CA 125 is related to tumor\nstage and histological subtype (14). In early ovarian\ncancer, CA 125 concentrations at initial diagnosis\nhave been shown to be of prognostic value for sur-\nvival (15). The aim of this study was to assess the\nprognostic value of preoperative CA 125 and CA 72-4\nin patients diagnosed with BOT.\nMaterials and methods\nPatients\nStudy group I Since different methods for measurement of\nCA 125 had been used over the long-time period that we\nevaluated, two different study groups were established.\nStudy group I comprised healthy women, BOT and ovarian\ncancer patients, and was used to validate the measurement\nof tumor markers using different testing systems.\nBereitgestellt von | Universitaetsbibliothek der LMU Muenchen\nAngemeldet | 129.187.254.47\nHeruntergeladen am | 14.11.13 15:27\n\n538 Lenhard et al.: Tumor markers in ovarian borderline tumors\nArticle in press - uncorrected proof\nIn addition, the concentration of tumor markers in BOT\npatients, patients with ovarian cancer and healthy women\nwere compared in this patient group. In total, this group con-\nsisted of 16 patients diagnosed with a BOT, 130 patients with\novarian cancer and 109 healthy women for whom blood\nserum samples were available. Statistical evaluation of this\ngroup assessed tumor marker concentrations, patient age,\nmenopause, tumor stage and histology.\nStudy group II All women diagnosed and treated for BOT\nbetween 1981 and 2008 at our institution were included in\nthe retrospective analysis. A total of 160 patients treated for\nBOT were identified. Of these 160 patients, tumor marker\nconcentrations had been measured preoperatively at our\ninstitution in 101 patients, who were assigned to study group\nII. For the remaining 59 patients, preoperative tumor marker\nmeasurements were either not performed or had been done\noutside our institution. Therefore, these patients were\nexcluded to ensure standardized analysis and comparability\nof results. In the retrospective evaluation, tumor marker con-\ncentrations were evaluated with respect to patient charac-\nteristics and clinical information including histology, tumor\nstage, endometriosis, ascites, menopausal status, relapse\nand survival.\nTumor markers Serum samples from patients included in\nstudy group I had been stored at –80 8C. CA 72-4 (Elecsys,\nRoche Diagnostics, Penzberg, Germany) and CA 125 (Archi-\ntect, Abbott Diagnostics, Chicago, US and Elecsys, Roche\nDiagnostics, Penzberg, Germany) were measured in patients\ndiagnosed with BOT (n s16), ovarian cancer (n s130) and\nhealthy women (n s109). CA 125 and CA 72-4 concentrations\nfor study group II had been measured at the time of primary\ndiagnosis using the kit in use at that time.\nHistology All patients underwent surgery by experienced\ngynecological surgeons at our institution. Typing and stag-\ning of tumors were performed by the Department of Patho-\nlogy according to the criteria of the International Federation\nof Gynaecologists and Obstetricians (FIGO) and the Interna-\ntional Union against Cancer (IUCC). Tumor, nodes, metas-\ntases (TNM) and FIGO stage, World Health Organization\n(WHO) grading and the presence of peritoneal implants were\nrecorded.\nFollow-up Clinical data, demographic, diagnostic and treat-\nment information were obtained primarily from the patients’\ncharts. The following parameters were recorded for each\npatient at initial diagnosis: age, menopausal status, and his-\ntory of endometriosis.\nDuring follow-up, patients were seen every 3 months fol-\nlowing initial diagnosis for a period of three years, then at\nsix-month intervals for an additional two years, and then\nonce a year. Patients were evaluated sonographically for\nsigns of relapse and tumor markers were measured at each\nfollow-up visit. If a relapse was suspected (e.g., a persisting\nsuspicious adnexal mass found at sonography or a contin-\nuous rise in tumor markers) surgery was performed to\nachieve a histological diagnosis. The occurrence of relapse,\ntime to relapse, death and survival time were recorded. Dis-\nease recurrence and survival were the primary outcomes\nassessed.\nStatistics Statistical analysis was performed using SAS\nV9.1 (SAS Institute Inc., Cary, NC, USA). Tumor marker con-\ncentrations are expressed as median and range. Differences\nbetween subgroups of group I and II were evaluated using\nthe Wilcoxon test. For comparison of relapse and survival\ntimes in group II, Kaplan-Meier curves were constructed.\nTwo groups were differentiated using median tumor marker\nvalues as cut-off points, and the x\n2 statistic of the log-rank\ntest was calculated to test for differences between survival\ncurves. For regression analysis, the PHREG procedure was\nperformed based on the Cox proportional hazard model.\nTumor marker values were transformed to the logarithm\nbase 2 scale as predictors. p-Values -0.05 were considered\nstatistically significant.\nResults\nStudy group I\nMedian age of patients at diagnosis of BOT was\n59.6 years (range 23.6–88.3 years), for ovarian cancer\n62.8 years (range 22.7–88.2 years). These reflect rep-\nresentative ages for diagnosis of an ovarian border-\nline or ovarian cancer. Median age for the group of\nhealthy women was 38.4 years (range 21.5–80.0\nyears). Due to the higher median age in the ovarian\ncancer patients and BOT group, there was a higher\nrate of postmenopausal women (81.3% in BOT, 78.5%\nin ovarian cancer patients vs. 19.2% in healthy wom-\nen). Histological stage was determined to be stage I\nin 15 (93.8%) and stage III in one (6.2%) of the BOT\npatients. For patients diagnosed with ovarian cancer,\n22 (16.9%) had stage I disease, stage II in 15 (11.5%),\nstage III in 83 (63.8%) and stage IV in 10 patients\n(7.7%) (Table 1).\nAll samples were tested for CA 125 using two dif-\nferent test systems (Architect, Abbott and Elecsys,\nRoche). Significantly different CA 125 concentrations\nwere observed between patients with a diagnosis of\novarian cancer, BOT, and healthy women. Results for\nBOT showed a median value of 34.7 U/mL (range\n18.1–385 U/mL) measured with the Architect and\n36.6 U/mL (range 17.3–332 U/mL) using the Elecsys\nsystem. Results for CA 125 in BOT patients, obtained\nusing either system, were comparable and not statis-\ntically different (p )0.05). However, for cancer\npatients, median CA 125 was 401.5 U/mL (range\n12.5–35,813 U/mL) with the Architect and 391.5 U/mL\n(range 13–27,070 U/mL) with the Elecsys system\n(p-0.001) (Table 1). Healthy women had a median CA\n125 of 13.5 U/mL (range 4.0–49.7 U/mL) using the\nArchitect and 11.9 U/mL (range 3.2–68.8 U/mL) using\nthe Elecsys system (p -0.001). Interestingly, for both\ntumor markers none of the patients diagnosed with\nBOT or ovarian cancer had CA 125 levels below 10\nU/mL, while more than 50% of healthy women\nshowed CA 125 levels below 10 U/mL.\nHealthy women had significantly lower CA 72-4,\nmedian 0.8 U/mL (range 0.2–20.6 U/mL), compared to\nBOT and ovarian cancer patients (p s0.03) (Table 1).\nThere was no significant difference between CA 72-4\nconcentrations in patients with BOT (median 2.3\nU/mL) and ovarian cancer (3.9 U/mL) (p s0.29).\nComparison of tumor marker concentrations meas-\nured in the same samples from individuals in group I\nusing the different test systems showed no significant\ndifferences. Thus, the different testing systems used\nfor tumor marker measurement in group II over the\nBereitgestellt von | Universitaetsbibliothek der LMU Muenchen\nAngemeldet | 129.187.254.47\nHeruntergeladen am | 14.11.13 15:27\n\nLenhard et al.: Tumor markers in ovarian borderline tumors 539\nArticle in press - uncorrected proof\nTable 1 Patient characteristics of study group I comparing patients with BOT (borderline ovarian tumor), Ov CA (ovarian\ncancer) and healthy women.\nPatient characteristics BOT Ov CA Healthy women\nn 16 130 109\nAge (median), years 59.6 62.8 38.3\nPremenopausal, % 18.7 21.5 80.2\nPostmenopausal, % 81.3 78.5 19.8\nStage I, n 15 22\nStage II, n 0 15\nStage III, n 1 83\nStage IV, n 0 10\nCA 125 U/mL (median, range)\nArchitect, Abbott 34.7 (18.1–385.0) 401.5 (12.5–35,813) 13.5 (4.0–49.7)\nElecsys, Roche 36.6 (17.3–332.0) 391.5 (13–27,070) 11.9 (3.2–68.8)\nCA 72-4 U/mL (median, range)\nElecsys, Roche 2.3 (0.2–277) 3.9 (0.3–10068) 0.8 (0.2–20.6)\nTable 2 Patient characteristics of study group II.\nPatients, n 101\nAge (median), years 53 years (range 18–88)\nMenopausal stage, %\nPremenopausal 61.5\nPostmenopausal 38.5\nHistology, %\nSerous 63.0\nMucinous 36.3\nEndometrioid 1.0\nTumor stage, %\npT1a 62.2\n)pT1a 37.8\nAscites, % 10.8\nPeritoneal implants, %\nAll 9.9\nInvasive 8.9\nEndometriosis, % 9.9\nFollow-up (median) years 6.3 \"4.6 years\n(minimum 3 months,\nmaximum 19.9 years)\nRelapse, % 5.0\nDeaths, % 5.0\nyears that this study encompassed should not have\nany effect on the retrospective data evaluation of\ngroup II study patients.\nStudy group II\nTumor marker measurements and surgery was per-\nformed on 101 patients with BOT. Mean (SD) follow-\nup time was 6.3 (4.6) years (minimum three months,\nmaximum 19.9 years). Relapse occurred during the\nfollow-up period in five patients (4.95%) with a mean\ntime to recurrence of 2.5 (16.0) years (minimum three\nmonths, maximum 4.6 years). Five deaths (4.95%)\noccurred, although it was not known if these were\ntumor-related. Median age at primary diagnosis was\n53 years (range 18–88 years) and 61.5% of patients\nwere premenopausal. Histology revealed a serous\ntumor in 63% of patients, mucinous in 36%, and endo-\nmetrioid in one patient. Table 2 shows that 62.2% of\nall patients were diagnosed at an early tumor stage\n(pT1a).\nIncreased tumor marker concentrations were found\nin 51.5% of BOT patients. Patients with increased CA\n125 and CA 72-4 did not show any statistical differ-\nence with regard to menopausal status or histological\nsubtype (p)0.05) (Table 3). Patients with tumor stage\npT1a had significantly lower values for CA 125 but not\nfor CA 72-4 compared to those with higher tumor\nstages (CA 125: 29.9 U/mL for pT1a vs. 50.9 U/mL for\nhigher stages; p s0.014; CA 72-4: 1.7 U/mL vs. 2.3\nU/mL; p s0.165).\nThere was a trend for increased concentrations of\nCA 125, but not of CA 72-4, in the presence of ascites\n(CA 125, p s0.289; CA 72-4, p s0.686) endometriosis\n(CA 125, p s0.116; CA 72-4, p s0.697) or peritoneal\nimplants (CA 125, p s0.057; CA 72-4, p s0.928) at pri-\nmary diagnosis.\nThe prognostic value of CA 125 was significantly\nhigher at initial diagnosis in patients who later devel-\noped recurrent disease (251.0 U/mL vs. 34.65 U/mL,\nps0.012). Similar findings were also observed for CA\n72-4 (p s0.093). Kaplan-Meier curves for CA 125 and\nCA 72-4 revealed a significant relationship between\nrelapse and elevated CA 125 (Log-rank test, CA 125:\ncut-off 35 U/mL, p s0.0368; CA 72-4: cut-off 1.9 U/mL,\nps0.0976) (Figures 1 and 2). Cox regression model\nanalysis showed the doubling of CA 125 to be asso-\nciated with a 2.261-fold risk of disease recurrence (CA\n125: p s0.0039, hazard ratio (HR) 2.26, 95% HR confi-\ndence interval (CI) 1.30–3.93; CA 72-4: p s0.1977, HR\n1.27, 95% HR CI 0.88–1.82). However, no statistically\nsignificant findings were found for overall survival.\nDiscussion\nInformation on the association of preoperative tumor\nmarker findings and BOT is very limited (16, 17). Stud-\nies of CA 125 have shown increased tumor marker\nconcentrations in BOT as well as in patients with ovar-\nian cancer (18). Our data confirm that serum CA 125\nand CA 72-4 in patients with BOT differ in median val-\nues from healthy controls and patients with ovarian\ncancer. The latter group generally shows the highest\nconcentration of CA 125 and CA 72-4; lowest concen-\ntrations seen in healthy women. Data from the liter-\nature suggest that the prevalence of BOT patients\nwith increased tumor marker concentrations varies\nbetween 15% and 50% (19). These data are further\nBereitgestellt von | Universitaetsbibliothek der LMU Muenchen\nAngemeldet | 129.187.254.47\nHeruntergeladen am | 14.11.13 15:27\n\n540 Lenhard et al.: Tumor markers in ovarian borderline tumors\nArticle in press - uncorrected proof\nTable 3 CA 125 and CA 72-4 concentrations according to menopausal stage, histology, tumor stage, presence of ascites,\nperitoneal implants and endometriosis.\nCA 125 U/mL (median, range) CA 72-4 U/mL (median, range)\nMenopausal status\nPremenopausal 36.9 (2.6–1996) 1.95 (0.4–396)\nPostmenopausal 29.5 (7.3–418) p s0.668 2.0 (0.2–396) p s0.406\nHistology\nSerous 35.2 (2.6–1996) 1.7 (0.2–396)\nMucinous 36.1 (7.0–418) p s0.647 2.3 (0.2–277) p s0.243\nEndometrioid 427.0 42.0\nTumor stage\npT1a 29.9 (2.6–454) 1.7 (0.2–230)\n)pT1a 50.9 (7.3–1996) p -0.01\na 2.3 (0.2–396) p s0.165\nAscites\nYes 62.8 (2.6–1996) 2.2 (0.5–396)\nNo 35.2 (7.0–418) p s0.029 1.9 (0.2–277) p s0.687\nImplantation\nYes 122.5 (7.3–1996) 2.2 (0.2–396)\nNo 35.3 (2.6–529) p s0.06 1.85 (0.4–277) p s0.929\nEndometriosis\nYes 98.6 (17.6–418) 1.7 (0.5–7.2)\nNo 35.3 (2.6–1996) p s0.12 2.0 (0.2–396) p s0.697\naStatistically significant.\nFigure 1 Relapse-free patients with reference to CA 125.\nFigure 2 Relapse-free patients with reference to CA 72-4.\nsupported by our study which showed tumor marker\nincreases in 51.5% of BOT patients. It has been pre-\nviously reported that CA 125 is often not released in\npatients with mucinous tumors (20), though our data\nshowed comparable results for mucinous and serous\ntumors.\nTo date, the diagnosis of a BOT cannot be made\nsolely with CA 125 and CA 72-4 measurements\nbecause of the considerable variability and overlap\nbetween patients with ovarian cancer and healthy\nindividuals. We found that CA 125, but not CA 72-4,\ncorrelates with tumor stage at initial diagnosis. Also\nCA 125 tends to be increased in the presence of asci-\ntes, endometriosis or peritoneal implants. Data from\nthe literature suggest that 80%–85% of patients with\nadvanced stages of ovarian cancer show increased\nconcentrations of CA 125, while only 50% with stage\nI disease show such increases (14, 21).\nOur findings may differ if results were interpreted\nwith respect to normal baseline values rather than\ncut-off thresholds. Normally, baseline CA 125 and CA\n72-4 measurements are not performed in healthy\nwomen, making it difficult to test this hypothesis.\nHowever, there are data showing that CA 125 levels\nrise over time in patients with BOT, before the tumor\nbecomes clinically evident and is diagnosed (18).\nSince we know that CA 125 and CA 72-4 concentra-\ntions are increased in patients with BOT, knowledge\nof a persistent increase in tumor marker concentra-\ntions in these women might be helpful in establishing\na diagnosis. In addition, we have shown that CA 125\ncan be useful as a good negative predictor since all\npatients diagnosed with BOT or ovarian cancer had\nCA 125 levels above 10 U/mL, but more than 50% of\nhealthy women showed CA 125 levels below 10 U/mL.\nThis may be especially useful when confronted with\nBereitgestellt von | Universitaetsbibliothek der LMU Muenchen\nAngemeldet | 129.187.254.47\nHeruntergeladen am | 14.11.13 15:27\n\nLenhard et al.: Tumor markers in ovarian borderline tumors 541\nArticle in press - uncorrected proof\nunclear sonographic imaging findings where CA 125\ncan be useful for identifying patients at low-risk for\nBOT or ovarian cancer.\nThe interpretation of increased tumor marker con-\ncentrations is still difficult because it is known to be\ninfluenced by inflammation, endometriosis, liver dis-\nease, and ovulation, and also differs in pre- and post-\nmenopausal women (13, 22). The high rate of\nfalse-positive results make interpretation of CA 125\nand CA 72-4, alone, difficult in gynecological patients\n(22). Therefore, combination with sonography and\nclinical exam remains essential for diagnosis and\ndecision making.\nAlthough, patients diagnosed with BOT generally\nhave a good prognosis, recurrence can occur. The\nrate of recurrence in BOT is rather low, with a relapse\nrate of 5% in this study group, compared to published\ndata showing rates of 15%–20% (23). At present, the\nidentification of patients at risk for recurrence of BOT\nremains uncertain. Morice et al. found patients with\ninvasive implants to have higher relapse rates (11).\nOur data show CA 125 elevation at initial diagnosis to\nbe of prognostic value for recurrence. Therefore, CA\n125 and CA 72-4 in addition to being helpful in the\ndiagnosis of BOT, might even be useful for the iden-\ntification of patients at risk for disease recurrence by\nallowing appropriate follow-up intervals to be estab-\nlished, since even late recurrence has been described\n(12).\nThe role of tumor markers for early detection of dis-\nease recurrence during clinical follow-up remains dif-\nficult. Rustin et al. found that an increase in serum CA\n125 to more than twice the upper limit of normal dur-\ning follow-up in patients with ovarian cancer after first\nline chemotherapy accurately predicts tumor relapse\n(24). Gotlieb et al., studying patients with BOT,\nshowed that increased concentrations of CA 125 can\nindicate relapse, although increases did not occur in\nall patients with relapse (16). Zanetta et al. described\nincreases in CA 125 above the cut-off in only 17% of\npatients at the time of relapse (25). This finding is in\nagreement with our data, as we also observed that\nnot all patients with recurrent disease showed an\nincrease in CA 125. However, it is not clear whether\nearly diagnosis of recurrent disease is of prognostic\nadvantage. Since better data are not available, clinical\nexamination, ultrasound and tumor marker measure-\nment remain the basis for clinical follow-up of\npatients with BOT.\nThe strength of this study is the long-term follow-\nup of patients (27 years), the high standard of surgery\nby gynecologic oncologists at a specialized academic\ninstitution and histopathologic review by expert gyne-\ncologic oncology pathologists. A limitation is the ret-\nrospective study design.\nConclusions\nSerum CA 125 and 72-4 in patients with BOT differ in\nmedian values from healthy controls and ovarian can-\ncer patients. CA 125, but not CA 72-4, correlates with\ntumor stage at initial diagnosis and tends to be\nincreased in the presence of ascites, endometriosis or\nperitoneal implants. In addition, CA 125 concentra-\ntions at initial diagnosis appear to have prognostic\nvalue for disease recurrence. However, better analytic\ntools for the detection of BOT are desirable.\nReferences\n1. Barakat RR. Borderline tumors of the ovary. Obstet\nGynecol Clin North Am 1994;21:93–105.\n2. Scully RE. World Health Organization classification and\nnomenclature of ovarian cancer. Natl Cancer Inst Mono-\ngr 1975;42:5–7.\n3. Trope C, Kaern J. Management of borderline tumors of\nthe ovary: state of the art. Semin Oncol 1998;25:372–80.\n4. Trimble CL, Trimble EL. Management of epithelial ovar-\nian tumors of low malignant potential. Gynecol Oncol\n1994;55:S52–61.\n5. Kennedy AW, Hart WR. Ovarian papillary serous tumors\nof low malignant potential (serous borderline tumors). 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Zanetta G, Rota S, Chiari S, Bonazzi C, Bratina G, Man-\ngioni C. Behavior of borderline tumors with particular\ninterest to persistence, recurrence, and progression to\ninvasive carcinoma: a prospective study. J Clin Oncol\n2001;19:2658–64.\n24. Rustin GJ, Nelstrop AE, Tuxen MK, Lambert HE. Defining\nprogression of ovarian carcinoma during follow-up\naccording to CA 125: a North Thames Ovary Group\nStudy. Ann Oncol 1996;7:361–4.\n25. Zanetta G, Rota S, Lissoni A, Meni A, Brancatelli G, Buda\nA. Ultrasound, physical examination, and CA 125 meas-\nurement for the detection of recurrence after conserva-\ntive surgery for early borderline ovarian tumors.\nGynecol Oncol 2001;81:63–6.\nBereitgestellt von | Universitaetsbibliothek der LMU Muenchen\nAngemeldet | 129.187.254.47\nHeruntergeladen am | 14.11.13 15:27","source_license":"public-domain-us","license_restricted":false}