Immunohistochemistry expression of targeted therapies biomarkers in ovarian clear cell and endometrioid carcinomas (type I) and endometriosis.

Ovarian clear cell and endometrioid carcinomas (type I) are thought to develop from endometriosis. ARID1A loss of expression is known to be related to the promotion of the endometriosis carcinogenesis. Despite the diverse origins and prognosis of type I and type II carcinomas, surgery followed by platinum-based chemotherapy is the mainstay of treatment for both. Limited knowledge about the expression of targeted therapies' biomarkers prevents the use of such markers as potential guides for tailored treatment. This study aimed to evaluate the expression of ARID1A gene and target therapies biomarkers (VEGF, PD-L1, and PARP-1) in ovarian clear cell and endometrioid carcinomas and endometriosis, and its relationship with prognosis. Forty-six ovarian clear cell and endometrioid carcinomas, and 24 endometriosis foci samples retrieved from the same surgical specimens were studied. ARID1A, VEGF, PD-L1, and PARP-1 immunohistochemistry expression was compared in carcinomas and endometriosis with regard to the clinicopathological features and prognosis. We found that endometriosis was associated with increased rates of diagnosis of cancer in the initial stages (P = .008). Different levels of expression of all biomarkers were detected in clear cell and endometrioid carcinomas and endometriosis. However, only the VEGF expression level showed a significant increase in the carcinoma group when compared with endometriosis (P = .0002). PARP-1 overexpression correlated with worse progression-free survival (P = .03) and overall survival (P = .01). In conclusion, endometriosis and ovarian clear cell and endometrioid carcinomas exhibited ARID1A loss of expression, and VEGF, PD-L1, and PARP-1 expression. PARP-1 overexpression in clear cell and endometrioid carcinomas was associated with early recurrence and worse overall survival.

Endometriosis-Associated Ovarian Cancer: Population Characteristics and Prognosis.

OBJECTIVE: The aim of this study was to analyze and compare the clinicopathologic features and prognosis of clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (EOC) associated or not with endometriosis. METHODS: This was a reconstituted cohort study from a single-institution Brazilian cancer center approved under review board no. 68150617.7.0000.5404 with 50 patients with CCOC and EOC diagnosed between 1995 and 2016, followed up until 2017. Clinicopathologic characteristics and survival outcomes were analyzed. RESULT(S): There were 23 women (46%) with CCOC and 27 with EOC (54%); 80% of those women had histologic confirmation of endometriosis; 42% were nulliparous, and 42% were premenopausal; and cancer antigen 125 was elevated in both International Federation of Gynecology and Obstetrics stages I-II disease (mean, 614.7 Ui/mL; range, 3-6030 Ui/mL) or International Federation of Gynecology and Obstetrics stages III-IV disease (mean, 2361.2 Ui/mL; range, 8-12771 Ui/mL). Women with EOC were 7 years younger than those with CCOC. When associated with endometriosis, CCOCs were more likely diagnosed at earlier stages. Endometrioid ovarian carcinoma and CCOC at initial stage and EOC at advanced stage share similar good prognosis. Univariate analysis showed that CCOC not associated with endometriosis has worse overall survival (OS). However, multivariate analysis showed that only abnormally elevated levels of cancer antigen 125 and advanced stage at diagnosis were significantly associated with reduced progression-free survival. Tumor stage remains the only prognostic factor for OS. CONCLUSIONS: The presence of coexisting endometriosis did not change the prognosis of EOC but was associated with better OS in patients with CCOC. Patients with CCOC and EOC at initial stages and EOC at advanced stages have a good prognosis; however, CCOC at advanced stages had a sooner recurrence and shorter OS.

Carcinomas de ovário associados à endometriose: expressão de marcadores proteicos de terapia alvo e prognóstico / Endometriosis-associated ovarian carcinomas: expression of protein biomarkers associated to target therapies and prognosis

Resumo: Introdução: endometriose é uma doença benigna, capaz de progredir extensamente e gerar clones atípicos. Considerada precursora dos carcinomas de células claras (CCOC) e endometrióide (EOC) de ovário, atualmente chamados carcinomas de ovário associados à endometriose (EAOC). Objetivos: comparar o perfil epidemiológico, a associação com endometriose e a expressão de marcadores imuno-histoquímicos para ARID1A, VEGF, PD-L1 e PARP-1 em mulheres com CCOC e EOC, e sua correlação com a sobrevida livre de progressão (SLP) e sobrevida global (SG). Métodos: estudo de coorte reconstituída, com 50 casos incluídos de CCOC e EOC tratados no CAISM-UNICAMP entre 1995 até 2016, acompanhados até 02/2017. Microarranjos de tecido com amostras de CCOC, EOC e endometriose foram corados com anticorpos monoclonais contra ARID1A, e para os biomarcadores proteicos VEGF, PD-L1, PARP-1 através de imuno-histoquímica. A expressão de ARID1A foi classificada (0 a 100) conforme a porcentagem de células não coradas. A expressão de VEGF, PD-L1 e PARP-1 foi classificada (0 a 300) conforme a multiplicação da porcentagem de células coradas por um fator da intensidade de expressão (ausente=0; fraco=1; moderado=2; forte=3). Idade ao diagnóstico; menopausa; índice de massa corpórea (IMC); CA-125; diagnóstico de endometriose; datas do diagnóstico, da progressão, do óbito e da última consulta foram recuperados dos prontuários. Comparação entre grupos foi realizada através de testes T e de ?2. A SLP (diferença de tempo entre o diagnóstico e a data de progressão) e a SG (diferença de tempo entre o diagnóstico e o óbito ou data da última data de consulta) foi avaliada através de curvas de Kaplan-Meyer e teste de Log-Rank ou regressão de COX. Resultados: 23 mulheres com CCOC (46%), e 27 com EOC (54%) foram incluídas; 80% tinham endometriose associada, 42% eram nulíparas, 42% eram pré-menopausa e CA125 foi elevado em todos estádios (FIGO I-II= média 614.7Ui/mL; FIGO III-IV= media 2361.2Ui/mL). A média de idade ao diagnóstico foi 7 anos menor em mulheres com EOC do que naquelas com CCOC. O CCOC foi mais diagnosticado em estágios iniciais quando associado à endometriose (p=0,03). O prognóstico dos EOC e CCOC em estádios iniciais foi semelhante (p=0,96). Os CCOC não associado à endometriose tiveram menor SG (p=0,04). A expressão de todos os biomarcadores esteve presente nos EAOC e na endometriose. O aumento da expressão de VEGF entre endometriose e câncer foi significativo (p=0,0002). A hiperexpressão de PARP-1 correlacionou-se negativamente com a SLP (p=0,03) e SG (p=0,01) em estádios iniciais. Conclusão: Os CCOC e EOC são comumente diagnosticados em estádios iniciais (FIGO I-II= 68%) e estão frequentemente associados à endometriose (80% dos casos). Quando associados à endometriose, os CCOC foram mais diagnosticados em estádios iniciais e tiveram SG maior. Houve elevada porcentagem de células com ARID1A mutado nos EAOC (>40%). VEGF se expressou mais intensamente nos CCOC e EOC que na endometriose, já a expressão de PD-L1 e de PARP-1 foi similar. Apenas a hiperexpressão de PARP-1 reduziu significativamente a SLP e a SG nos CCOC e EOC nos estádios iniciais(AU)

Abstract: Introduction: Endometriosis is a benign disease, able to progress widely and generate atypical clones. It is a precursor of clear cell ovarian carcinomas (CCOC) and endometrioid ovarian carcinomas (EOCs), now called endometriosis-associated ovarian carcinomas (EAOC). Objectives: To compare the epidemiological profile, association with endometriosis and the expression of immunohistochemical markers for ARID1A, VEGF, PD-L1 and PARP-1 in women with CCOC and EOC, and its correlation with progression-free survival (PFS) and overall survival (OS). Methods: A reconstituted cohort study with 50 cases of CCOC and EOC included. Cases were treated at CAISM-UNICAMP between 1995 and 2016, followed up until 02/2017. Tissue microarrays with CCOC, EOC and endometriosis samples were stained with monoclonal antibodies against ARID1A, and for VEGF, PD-L1, PARP-1 biomarkers by immunohistochemistry. The expression of ARID1A was classified (0 to 100) according to the percentage of unstained cells. The expression of VEGF, PD-L1 and PARP-1 was classified (0 to 300) multiplying the percentage of stained cells by an intensity of expression factor (absent=0, weak=1, moderate=2, strong=3). Age at diagnosis; menopause; BMI (body mass index); CA-125 levels; diagnosis of endometriosis; date of diagnosis, date of progression, date of death and date of last consultation were retrieved from the medical records. Comparison between groups was performed through T and ?2 tests. The PFS (difference in time between diagnosis and progression date) and OS (difference in time between diagnosis and death or the last date of consultation) was assessed using Kaplan-Meyer curves and Log-Rank test or COX multivariate models. Results: twenty-three women with CCOC (46%), and 27 with EOC (54%) were included; 80% had associated endometriosis, 42% were nulliparous, 42% were premenopausal, and CA125 was elevated at all stages (FIGO I-II = mean 614.7Ui / mL; FIGO III-IV = mean 2361.2Ui / mL). The mean age at diagnosis was 7 years lower in women with EOC than in those with CCOC. CCOC when associated with endometriosis were more diagnosed at early stages (p=0.03). The prognosis of EOC and CCOC at early stages was similar (p=0.96). CCOCs not associated with endometriosis had shorter OS (p=0.04). Expression of all biomarkers was present in the EAOC and endometriosis. The increase in VEGF expression between endometriosis and cancer was significant (p=0.0002). The overexpression of PARP-1 correlated negatively with PFS (p=0.03) and OS (p=0.01) at FIGO I-II stages. Conclusion: The diagnosis of women with EOC was made earlier than in those with CCOC. CCOC and EOC are commonly diagnosed in early stages (FIGO I-II - 68%) and were associated with endometriosis (80% of cases). When associated with endometriosis, clear cell carcinomas are more likely diagnosed at early stages, and the association of endometriosis with CCOC improves OS. There was a high percentage of cells with mutated ARID1A gene in EAOC (> 40%). VEGF was expressed more intensely in CCOC and EOC than in endometriosis, whereas expression of PD-L1 and PARP-1 was similar. Only the overexpression of PARP-1 significantly reduced PFS and OS in CCOC and EOC at early stages(AU)

Criteria for selection of laparoscopy for women with adnexal mass.

OBJECTIVES: We compared the indication of laparoscopy for treatment of adnexal masses based on the risk scores and tumor diameters with the indication based on gynecology-oncologists' experience. METHODS: This was a prospective study of 174 women who underwent surgery for adnexal tumors (116 laparotomies, 58 laparoscopies). The surgeries begun and completed by laparoscopy, with benign pathologic diagnosis, were considered successful. Laparoscopic surgeries that required conversion to laparotomy, led to a malignant diagnosis, or facilitated cyst rupture were considered failures. Two groups were defined for laparoscopy indication: (1) absence of American College of Obstetrics and Gynecology (ACOG) guideline for referral of high-risk adnexal masses criteria (ACOG negative) associated with 3 different tumor sizes (10, 12, and 14 cm); and (2) Index of Risk of Malignancy (IRM) with cutoffs at 100, 200, and 300, associated with the same 3 tumor sizes. Both groups were compared with the indication based on the surgeon's experience to verify whether the selection based on strict rules would improve the rate of successful laparoscopy. RESULTS: ACOG-negative and tumors≤10 cm and IRM with a cutoff at 300 points and tumors≤10 cm resulted in the same best performance (78% success=38/49 laparoscopies). However, compared with the results of the gynecology-oncologists' experience, those were not statistically significant. DISCUSSION: The selection of patients with adnexal mass to laparoscopy by the use of the ACOG guideline or IRM associated with tumor diameter had similar performance as the experience of gynecology-oncologists. Both methods are reproducible and easy to apply to all women with adnexal masses and could be used by general gynecologists to select women for laparoscopic surgery; however, referral to a gynecology-oncologist is advisable when there is any doubt.

[Laparoscopy for diagnosis and treatment of adnexal masses]. / Laparoscopia na abordagem inicial de tumores anexiais.

PURPOSE: To assess clinical factors, histopathologic diagnoses, operative time and differences in complication rates between women undergoing laparoscopy or laparotomy to diagnose and treat an adnexal mass and their association with laparoscopy failure. METHODS: In this prospective study, 210 women were invited to participate and 133 of them were included. Eighty-eight women underwent laparotomy and 45 underwent laparoscopy. Fourteen of the 45 laparoscopies were converted to laparotomy intraoperatively. We assessed whether age, body mass index (BMI), previous abdominal surgeries, CA-125, Index of Risk of Malignancy (IRM), tumor diameter, histological diagnosis, operative time and surgical complication rates differed between the laparoscopy group and the group converted to laparotomy and whether those factors were associated with conversion of laparoscopy to laparotomy. We also assessed surgical logs to evaluate the reasons, as stated by the surgeons, to convert a laparoscopy to laparotomy. RESULTS: In this research, 30% of the women had malignant tumors. CA-125, IRM, tumor diameter and operative times were higher for the laparotomy group than the laparoscopy group. Complication rates were similar for both groups and also for the successful laparoscopy and unsuccessful laparoscopy groups. The surgical complication rate in women with benign tumors was lower for the laparoscopy group than for the laparotomy group. The factors associated with conversion to laparotomy were tumor diameter and malignancy. During laparoscopy, adhesions a large tumor diameter were the principal causes of conversion. CONCLUSION: This study suggests that laparoscopy for the diagnosis and treatment of adnexal masses is safe and does not increase complication rates even in patients who need conversion to laparotomy. However, when doubt about the safety of the procedure and about the presence of malignancy persists, consultation with an expert gynecology-oncologist with experience in advanced laparoscopy is recommended. A large tumor diameter was associated with the necessity of conversion to laparotomy.

Laparoscopia na abordagem inicial de tumores anexiais / Laparoscopy for diagnosis and treatment of adnexal masses

OBJETIVO: Avaliar o uso da laparoscopia como método diagnóstico e terapêutico na abordagem inicial de tumores anexiais em população de risco para malignidade, bem como fatores clínicos associados à falha do método e conversão para laparotomia, e comparar taxas de complicação com pacientes cuja abordagem inicial se deu por laparotomia. MÉTODOS: Estudo prospectivo com 210 mulheres com exames de imagem prévios constando tumor anexial, das quais 133 foram incluídas. Destas, 45 foram submetidas à laparoscopia e 88, à laparotomia. Catorze das 45 cirurgias iniciadas por laparoscopia foram convertidas a laparotomia no intraoperatório. Foi avaliado se idade, índice de massa corporal (IMC), número de cirurgias abdominais prévias, CA-125, índice de risco de malignidade (IRM), diâmetro do tumor, duração da cirurgia e número de complicações cirúrgicas diferiram entre os grupos laparoscopia, laparoscopia com conversão à laparotomia e laparotomia. Foi também avaliado o motivo reportado pelos cirurgiões como falha da laparoscopia e a razão da conversão para laparotomia. RESULTADOS: A taxa de tumores malignos neste estudo foi de 30%. Houve diferença nos valores de CA-125, IRM e diâmetro do tumor entre os grupos laparoscopia e laparotomia. A duração da cirurgia foi maior no grupo de laparoscopias convertidas à laparotomia, porém as taxas de complicação cirúrgica foram semelhantes entre os grupos e, quando isolados os tumores benignos, as taxas de complicação cirúrgica da laparoscopia se mostraram inferiores à laparotomia. Dentre os fatores em estudo, apenas o tamanho do tumor esteve relacionado à conversão para laparotomia. CONCLUSÃO: Este estudo sugere que a abordagem inicial de pacientes com tumores ...

PURPOSE: To assess clinical factors, histopathologic diagnoses, operative time and differences in complication rates between women undergoing laparoscopy or laparotomy to diagnose and treat an adnexal mass and their association with laparoscopy failure. METHODS: In this prospective study, 210 women were invited to participate and 133 of them were included. Eighty-eight women underwent laparotomy and 45 underwent laparoscopy. Fourteen of the 45 laparoscopies were converted to laparotomy intraoperatively. We assessed whether age, body mass index (BMI), previous abdominal surgeries, CA-125, Index of Risk of Malignancy (IRM), tumor diameter, histological diagnosis, operative time and surgical complication rates differed between the laparoscopy group and the group converted to laparotomy and whether those factors were associated with conversion of laparoscopy to laparotomy. We also assessed surgical logs to evaluate the reasons, as stated by the surgeons, to convert a laparoscopy to laparotomy. RESULTS: In this research, 30% of the women had malignant tumors. CA-125, IRM, tumor diameter and operative times were higher for the laparotomy group than the laparoscopy group. Complication rates were similar for both groups and also for the successful laparoscopy and unsuccessful laparoscopy groups. The surgical complication rate in women with benign tumors was lower for the laparoscopy group than for the laparotomy group. The factors associated with conversion to laparotomy were tumor diameter and malignancy. During laparoscopy, adhesions a large tumor diameter were the principal causes of conversion. CONCLUSION: This study suggests that laparoscopy for the diagnosis and treatment of adnexal masses is safe and does not increase complication rates even in patients who need conversion to laparotomy. However, when doubt about the safety of the procedure and about the presence of malignancy persists, consultation with an expert gynecology-oncologist ...

Symptoms, CA125 and HE4 for the preoperative prediction of ovarian malignancy in Brazilian women with ovarian masses.

BACKGROUND: This manuscript evaluates whether specific symptoms, a symptom index (SI), CA125 and HE4 can help identify women with malignant tumors in the group of women with adnexal masses previously diagnosed with ultrasound. METHODS: This was a cross-sectional study with data collection between January 2010 and January 2012. We invited 176 women with adnexal masses of suspected ovarian origin, attending the hospital of the Department of Obstetrics and Gynecology of the Unicamp School of Medicine. A control group of 150 healthy women was also enrolled. Symptoms were assessed with a questionnaire tested previously. Women with adnexal masses were interviewed before surgery to avoid recall bias. The Ward Agglomerative Method was used to define symptom clusters. Serum measurements of CA125 and HE4 were made. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using standard formulae. RESULTS: Sixty women had ovarian cancer and 116 benign ovarian tumors. Six symptom clusters were formed and three specific symptoms (back pain, leg swelling and able to feel abdominal mass) did not agglomerate. A symptom index (SI) using clusters abdomen, pain and eating was formed. The sensitivity of the SI in discriminating women with malignant from those with benign ovarian tumors was 78.3%, with a specificity of 60.3%. Positive SI was more frequent in women with malignant than in women with benign tumors (OR 5.5; 95% CI 2.7 to 11.3). Elevated CA125 (OR 11.8; 95% CI 5.6 to 24.6) or HE4 (OR 7.6; 95% CI 3.7 to 15.6) or positive ROMA (OR 9.5; 95% CI 4.4 to 20.3) were found in women with malignant tumors compared with women with benign tumors. The AUC-ROC for CA125 was not different from that for HE4 or ROMA. The best specificity and negative predictive values were obtained using CA125 in women with negative SI. CONCLUSION: Women diagnosed with an adnexal mass could benefit from a short enquiry about presence, frequency and onset of six symptoms, and CA125 measurements. Primary care physicians can be thereby assisted in deciding as to whether or not reference the woman to often busy, congested specialized oncology centers.

Inclusão dos sintomas na discriminação entre tumores anexiais benignos e malignos / Inclusion of symptoms in the discrimination between benign and malignant adnexal masses

OBJETIVO: Avaliar a associação entre sintomas clínicos e malignidade em mulheres com tumores anexiais, submetidas à cirurgia. MÉTODOS: Estudo de corte transversal com coleta prospectiva, no qual foram incluídas 105 mulheres, atendidas em um hospital de ensino do Estado de São Paulo de novembro de 2009 a março de 2011, devido ao tumor anexial e à indicação de laparotomia/laparoscopia. Todas foram submetidas a uma entrevista estruturada sobre a ocorrência de 18 sintomas associados ao câncer de ovário. A entrevista incluiu gravidade, frequência e duração dos sintomas nos 12 meses prévios à primeira consulta. Também foram avaliados os níveis de CA125 e a classificação ultrassonográfica. Foi calculada para cada sintoma a razão de prevalência com intervalo de confiança de 95%. O padrão-ouro foi o resultado do exame anatomopatológico das peças cirúrgicas. RESULTADOS: Das 105 mulheres incluídas, 75 (71,4%) apresentaram tumores benignos e 30 (28,6%), malignos. Em mulheres com tumores malignos, os sintomas foram mais frequentes, dentre eles: inchaço abdominal (70%), aumento do volume abdominal (67%), dor pélvica (60%), irregularidade menstrual (60%), empachamento (53%), dor abdominal (50%), dor nas costas (50%) e saciedade precoce (50%). As mulheres com tumores benignos apresentaram essencialmente dor pélvica (61%), irregularidade menstrual (61%) e inchaço abdominal (47%). Os sintomas significativamente associados com malignidade foram: sensação de inchaço abdominal (RP=2,0; IC95% 1,01 - 3,94), aumento objetivo do volume abdominal (RP=2,16; IC95% 1,12 - 4,16), dor nas costas (RP=1,97; IC95% 1,09 - 3,55), empachamento (RP=2,25; IC95% 1,25 - 4,07), saciedade precoce (RP=2,06; IC95% 1,14 - 3,70), massa abdominal (RP=1,83; IC95% 1,01 - 3,30), dificuldade para deglutir (RP=1,98; IC95% 1,10 - 3,56) e sangramento pós-menopausa (RP=2,91; IC95% 1,55 - 5,44). A presença de dor pélvica, constipação, dispareunia, fadiga, dor abdominal, náusea e/ou vômito, irregularidade menstrual, perda de peso, diarreia e sinusorragia foram semelhantes nos dois grupos. CONCLUSÕES: Em mulheres com tumores anexiais com indicação cirúrgica, a avaliação pré-operatória dos sintomas pode auxiliar na predição da malignidade.

PURPOSE: To assess the association between clinical symptoms and the diagnosis of malignancy in women with adnexal tumors who underwent surgery. METHODS: Cross-sectional study, in which 105 women with adnexal tumors and indication for laparotomy/laparoscopy were included. All women were treated at a teaching hospital in the state of São Paulo between November 2009 and March 2011. All patients underwent a structured interview about the occurrence of 18 symptoms associated with ovarian cancer. The interview included the severity, frequency, and duration of these symptoms in the 12 months prior to the first medical consultation. The CA125 levels and the ultrasound classification of the tumors were also evaluated. We calculated for each symptom the prevalence ratio with 95% confidence intervals. The golden-standard was the result of the pathological examination of the surgical specimens. RESULTS: Of the 105 women included, 75 (71.4%) had benign tumors and 30 (28.6%) had malignant ones. In women with malignant tumors, the most frequent symptoms were: abdominal bloating (70%), increased abdominal size (67%), pelvic pain (60%), menstrual irregularity (60%), swelling (53%), abdominal pain (50%), backache (50%), and early repletion (50%). Women with benign tumors showed essentially pelvic pain (61%), menstrual irregularities (61%), and abdominal swelling (47%). Symptoms significantly associated with malignancy were: bloating (PR=2.0; 95%CI 1.01 - 3.94), increased abdominal size (PR=2.16; 95%CI 1.12 - 4.16), backache (RP=1.97; 95%CI 1.09 - 3.55), swelling (PR=2.25; 95%CI 1.25 - 4.07), early repletion (RP=2.06; 95%CI 1.14 - 3.70), abdominal mass (PR=1.83; 95%CI 1.01 - 3.30), eating difficulties (PR=1.98; 95%CI 1.10 - 3.56), and postmenopausal bleeding (PR=2.91; 95%CI 1.55 - 5.44). The presence of pelvic pain, constipation, dyspareunia, fatigue, abdominal pain, nausea or vomiting, menstrual irregularity, weight loss, diarrhea, and bleeding after intercourse was similar in both groups. CONCLUSIONS: In women with adnexal tumors including indication of surgical treatment, the preoperative evaluation of symptoms may help predicting malignancy.

[Inclusion of symptoms in the discrimination between benign and malignant adnexal masses]. / Inclusão dos sintomas na discriminação entre tumores anexiais benignos e malignos.

PURPOSE: To assess the association between clinical symptoms and the diagnosis of malignancy in women with adnexal tumors who underwent surgery. METHODS: Cross-sectional study, in which 105 women with adnexal tumors and indication for laparotomy/laparoscopy were included. All women were treated at a teaching hospital in the state of São Paulo between November 2009 and March 2011. All patients underwent a structured interview about the occurrence of 18 symptoms associated with ovarian cancer. The interview included the severity, frequency, and duration of these symptoms in the 12 months prior to the first medical consultation. The CA125 levels and the ultrasound classification of the tumors were also evaluated. We calculated for each symptom the prevalence ratio with 95% confidence intervals. The golden-standard was the result of the pathological examination of the surgical specimens. RESULTS: Of the 105 women included, 75 (71.4%) had benign tumors and 30 (28.6%) had malignant ones. In women with malignant tumors, the most frequent symptoms were: abdominal bloating (70%), increased abdominal size (67%), pelvic pain (60%), menstrual irregularity (60%), swelling (53%), abdominal pain (50%), backache (50%), and early repletion (50%). Women with benign tumors showed essentially pelvic pain (61%), menstrual irregularities (61%), and abdominal swelling (47%). Symptoms significantly associated with malignancy were: bloating (PR=2.0; 95%CI 1.01 - 3.94), increased abdominal size (PR=2.16; 95%CI 1.12 - 4.16), backache (RP=1.97; 95%CI 1.09 - 3.55), swelling (PR=2.25; 95%CI 1.25 - 4.07), early repletion (RP=2.06; 95%CI 1.14 - 3.70), abdominal mass (PR=1.83; 95%CI 1.01 - 3.30), eating difficulties (PR=1.98; 95%CI 1.10 - 3.56), and postmenopausal bleeding (PR=2.91; 95%CI 1.55 - 5.44). The presence of pelvic pain, constipation, dyspareunia, fatigue, abdominal pain, nausea or vomiting, menstrual irregularity, weight loss, diarrhea, and bleeding after intercourse was similar in both groups. CONCLUSIONS: In women with adnexal tumors including indication of surgical treatment, the preoperative evaluation of symptoms may help predicting malignancy.