Cell Cycle Regulator p27 Mediates Body Mass Index Effects in Ovarian Cancer in FIGO-stages I-II.

BACKGROUND/AIM: The aim of the present study was to evaluate the association between body mass index (BMI), the biomarker p27, and the clinical factors in FIGO-stages I-II ovarian cancer. PATIENTS AND METHODS: A total of 128 patients with ovarian cancer were included in the study. For testing differences in univariate analyzes we used the Pearson's Chi-square test and the log-rank test. For multivariate analyses the logistic regression and Cox regression models were used with recurrent disease and disease-free survival as endpoints, respectively. RESULTS: Patients with BMI ≤25 kg/m2 had a significantly better 5-year disease-free survival compared with patients with BMI >25 kg/m2 in the total series of patients (p=0.008), and in the series of patients (n=77) with non-serous tumors (p=0.047). Patients with p27-positive non-serous tumors had higher survival compared to patients with p27-negative non-serous tumors (p=0.020). CONCLUSION: The cell cycle regulator p27 mediates BMI effects in ovarian cancer in FIGO-stages I-II.

Clinical significance of growth factor receptor EGFR and angiogenesis regulator VEGF­R2 in patients with ovarian cancer at FIGO stages I-II.

The aim of the present retrospective cohort study was to investigate the prognostic effect of epidermal growth factor receptor (EGFR) and the angiogenesis regulator vascular endothelial growth factor receptor 2 (VEGF­R2) on disease-free survival (DFS) rate and recurrent disease, and their association with clinicopathological characteristics in 131 patients with International Federation of Gynecology and Obstetrics (FIGO) stages I-II epithelial ovarian cancer. The techniques of tissue microar-rays and immunohistochemistry were used for the positive detection of the markers. The frequency of positive staining in tumors for EGFR was 24% and for VEGF­R2 was 77%. Across the cohort, there was a total of 34/131 recurrences (26%) and the 5­year DFS rate was 68%. In a multivariate logistic regression analysis with recurrent disease as the endpoint, FIGO stage (OR=9.7), type (I/II) of tumor (OR=3.0) and VEGF­R2 status (OR=0.2) were all found to be independent predictive factors in the cohort of patients (n=131). For patients with non­serous tumors (n=78), the FIGO stage (OR=76), type (I/II) of tumor (OR=44), EGFR status (OR=0.05) and VEGF­R2 status (OR=0.008) were all significant and independent predictive factors. On comparing the four subgroups, in terms of concomitant EGFR and VEGF­R2 status, in a survival analysis, the subgroup of patients (n=21) with concomitant positive expression of EGFR and VEGF­R2 had a 5­year DFS rate of 100%. Therefore, the prognostic effect of EGFR and VEGF­R2 for recurrent disease and survival rates was confirmed by the above findings. Certain results in the present study were not in line with results from previous studies on the prognostic effect of EGFR and VEGF­R2. An increasing number of preclinical and clinical observations have shown that the process of angiogenesis remains to be fully elucidated. Therefore, one of the challenges for future ovarian cancer investigations is to identify which biomarkers may be used as predictive and prognostic markers.

The clinical and prognostic correlation of HRNPM and SLC1A5 in pathogenesis and prognosis in epithelial ovarian cancer.

OBJECTIVES: To evaluate the prognostic effect of the Heterogeneous nuclear ribonucleoprotein type M (HNRPM) and Solute carrier 1A5 (SLC1A5) in FIGO-stages I-II epithelial ovarian cancer. METHODS: A retrospective cohort study was designed to investigate the prognostic effect of HNRPM and SLC1A5, and the association with clinical-pathologic characteristics in 131 patients with FIGO-stages I-II epithelial ovarian cancer. Tissue microarrays were constructed and protein levels were assessed by immunohistochemistry (IHC). RESULTS: Positive HRNPM status was associated with positive staining for PUMA (P = 0.04), concomitant PUMA and p21 staining (P = 0.005), and VEGF-R2 (P = 0.003). Positive SLC1A5 staining was associated with positive staining of p27 (P = 0.030), PUMA (P = 0.039), concomitant PUMA and p27 staining, and VEGF-R2 (P = 0.039). In non-serous tumors (n = 72), the SLC1A5 positivity was associated with recurrent disease (P = 0.01). In a multivariable logistic regression analysis FIGO-stage (OR = 12.4), tumor grade (OR = 5.1) and SLC1A5 positivity (OR = 0.1) were independent predictive factors for recurrent disease. Disease-free survival (DFS) in women with SLC1A5-positive non-serous tumors was 92% compared with of 66% in patients with SLC1A5-negative non-serous tumors (Log-rank = 15.343; P = 0.008). In Cox analysis with DFS as endpoint, FIGO-stage (HR = 4.5) and SLC1A5 status (HR = 0.3) were prognostic factors. CONCLUSIONS: As the proteins HRNPM and SLC1A5 are associated with the cell cycle regulators p21 or p27, the apoptosis regulators PTEN and PUMA, and the VEGF-R2 it is concluded that both proteins have role in the pathogenesis of ovarian cancer. In patients with non-serous ovarian cancer SLC1A5 protects from recurrent disease, presumably by means of biological mechanisms that are unrelated to cytotoxic drug sensitivity.

The relationship of the angiogenesis regulators VEGF-A, VEGF-R1 and VEGF-R2 to p53 status and prognostic factors in epithelial ovarian carcinoma in FIGO-stages I-II.

The aim of this study was to evaluate prognostic effect of the angiogenesis regulators VEGF-R1, VEGF-R2 and VEGF-A for recurrent disease and disease-free survival (DFS), and their relation to the apoptosis regulator p53, in 131 patients with FIGO-stages I-II with epithelial ovarian cancer. For the detection of positivity of the markers the techniques of tissue microarrays and immunohistochemistry (IHC) were used. In tumors the frequency of positive staining for VEGF-R1 was 19%, for VEGF-R2 and VEGF-A, it was 77 and 70%, respectively. Positivity for p53 was detected in 25% of tumors. The total number of recurrences in the complete series was 34 out of 131 (26%) and 5-year disease-free survival (DFS) was 68%. Positive staining for VEGF-A (P=0.030), VEGF-R2 (P=0.011) and p53 (P=0.015) was found more frequently in type II tumors than in type I tumors. Patients with VEGF-R1 negative tumors had worse (P=0.021) DFS compared to patients with VEGF-R1 positive tumors. In two multivariate Cox analyzes with DFS as endpoint, FIGO-stage (HR=3.8), VEGF-R2 status (HR=0.4) and p53 status (HR=2.3), all were significant and independent prognostic factors. When the variables VEGF-R2 and p53 were replaced with the new variable VEGF-R2+p53-/other three combinations in one group, it was found that patients from that subgroup had 86% reduced risk of dying in disease (HR=0.24). Findings above, confirmed relationship between VEGF-R2 and VEGF-A and p53, respectively, with regard to recurrent disease and survival. Some findings from the present study are different from results from previous studies on the regulation of angiogenesis. Despite many trials with anti-angiogenic agents in the front line of ovarian cancer have shown to be positive for progression-free survival, no one has demonstrated an impact on overall survival. Therefore, one of the greatest challenges in ovarian cancer research, is to discover predictive and prognostic biomarkers.

Differences in Clinical and Biological Features Between Type I and Type II Tumors in FIGO Stages I-II Epithelial Ovarian Carcinoma.

OBJECTIVE: The objective of this study was to compare immunohistochemical profile for the apoptosis regulators p53, C-MYC, bax, PUMA, and PTEN and the cell cycle regulatory proteins p21 and p27, as well as clinical factors between types I and II tumors. METHODS: In total, 131 patients in FIGO (International Federation of Gynecology and Obstetrics) stages I-II were divided into 2 groups of patients after type I tumors (n = 79) and type II tumors (n = 52). Differences in the immunohistochemical profile for the cell cycle-related proteins, detected by tissue microarrays and immune-histochemistry, were compared. For statistical tests, the Pearson χ test and the logistic regression model were used. All tests were 2-sided, and the level of statistical significance was P ≤ 0.05. RESULTS: In multivariate logistic regression analysis with recurrent disease as endpoint, FIGO stage (odds ratio [OR], 4.7), type I/II tumors (OR, 3.8), body mass index (BMI) (OR, 3.5), and p53 status (OR, 4.2) all were found to be independent predictive factors. In 2 different multivariate logistic regression analyses with type I/II tumors as endpoint, both p53p21 (OR, 2.9) and p27 status (OR, 3.0) were associated with type II tumors. Differently, C-MYC status (OR, 0.4) was associated with type I tumors. Furthermore, age (OR, 1.04), BMI (OR, 0.4), and recurrent disease (OR, 4.3) all were associated to type II tumors. In survival analysis, there was a trend (P = 0.054) toward better disease-free survival for patients with type I tumors. CONCLUSIONS: Concomitant positivity for p53 and negativity for p21, positivity for p27, and negativity for C-MYC in an epithelial ovarian tumor might strengthen the diagnostic option of type II tumor ovarian carcinoma. Patients with type II tumors were older, had lower BMI, and had more often recurrent disease than patients with type I tumors.

Napsin A as a marker of clear cell ovarian carcinoma.

BACKGROUND: Clear cell carcinomas are aggressive tumors with a distinct biologic behaviour. In a genome-wide screening for genes involved in chemo-resistance, NAPA was over-expressed in cisplatin-resistant cells. The NAPA (protein) Napsin A was described to promote resistance to cisplatin by degradation of the tumor suppressor p53. METHODS: Totally 131 patients were included in this study all in FIGO-stages I-II; 16 were clear cell tumors which were compared with 40 Type I tumors and 75 type II tumors according to the markers Napsin A, p21, p53 and p27 and some clinical features. For detection of the markers tissue microarrays and immunohistochemistry were used. RESULTS: Positivity for Napsin A was detected in 12 (80%) out of the 15 clear cell tumors available for analysis compared with 3 (4%) out of the Type I and II tumors in one group (p<0.001). Differences in p21 status, p53 status, and p21+p53- status were striking when clear cell tumors were compared with Type I, Type II, and Type I and II tumors in one group, respectively. The p21+p53-status was associated to positive staining of Napsin A (p=0.0015) and clear cell morphology (p=0.0003). In two separate multivariate logistic regression analyses with Napsin A as endpoint both clear cell carcinoma with OR=153 (95% C.I. 21-1107); (p<001) and p21+p53- status with OR=5.36 (95% C.I. 1.6-17.5); (p=0.005) were independent predictive factors. ROC curves showed that AUC for Napsin A alone was 0.882, for p21+p53- it was 0.720 and for p21+p53-Napsin A+AUC was 0.795. Patients with clear cell tumors had lower (p=0.013) BMI than Type I patients and were younger (p=0.046) at diagnosis than Type II patients. Clear cell tumors had a higher frequency (p=0.039) of capsule rupture at surgery than Type I and II tumors. CONCLUSIONS: Positivity of Napsin A in an epithelial ovarian tumor might strengthen the morphological diagnosis of clear cell ovarian carcinoma in the process of differential diagnosis between clear cell ovarian tumors and other histological subtypes.

Association of p21, p21 p27 and p21 p53 status to histological subtypes and prognosis in low-stage epithelial ovarian cancer.

AIM: The objective of this study was to evaluate the prognostic value of p21 alone and in combination with p53 or p27 for different histological subtypes of epithelial ovarian cancer and disease-free survival. PATIENTS AND METHODS: The specimens were obtained at primary surgery from a series of 129 ovarian carcinomas in FIGO stages I-II. The technique of tissue microarray and immunohistochemistry was used for detection of positivity of the markers. RESULTS: Positive staining for p21, p27 and p53 was detected in 36%, 58% and 25% of cases, respectively. The p21 status, p27 status and concomitant p21 p27 and p21 p53 status in four subgroups were related to histological subtypes (p=0.016, p=0.036, p=0.004 and p=0.001). Mucinous tumors mostly stained negatively for p27 and concomitantly negatively for p21 and p53. Clear cell tumors generally stained positively for p21 and p27 but negatively for p53. Serous tumors usually stained concomitantly negatively for p21 and positively for p53. In a multivariate Cox regression analysis, FIGO stage, p21 p53 and p53 status were independent prognostic factors for disease-free survival. CONCLUSION: A subgroup, constituting 25/129 (19%) of the patients with predominantly serous tumors with concomitant p21 negativity and p53 positivity had a poor survival. Another subgroup of 11/129 (9%) patients with non-serous tumors with concomitant p21 and p27 positivity had excellent survival.

Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease.

BACKGROUND: Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome. METHODS: Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified. RESULTS: The most significant differences (p < 0.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8 Mbp (19 genes) and 51.5-53.0 Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56 Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56 Mbp) was significantly (p < 0.01) associated with loss of TP53 function. CONCLUSIONS: The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome.

Prognostic impact of concomitant p53 and PTEN on outcome in early stage (FIGO I-II) epithelial ovarian cancer.

INTRODUCTION: The objective of the study was to evaluate the prognostic effect of p53, PTEN, and concomitant p53 PTEN status on clinicopathologic features, recurrent disease, and disease-free survival (DFS) of 131 patients in FIGO stages I to II with epithelial ovarian cancer. METHODS: The technique of tissue microarray and immunohistochemistry was used for the detection of positivity of the biologic markers p53 and PTEN. RESULTS: In the complete series, the 5-year DFS rate was 68%, and the overall survival rate was 71%. Positive staining for p53 and PTEN was detected in 25% and 22% of cases, respectively. Positivity of p53 was associated with tumor grade in the total series but not in the subgroup of serous tumors. In survival analysis, there was worse survival (P = 0.003) in the group of patients with p53-positive tumors compared with the group of patients with p53-negative tumors with DFS of 62% and 82%, respectively. Furthermore, DFS was 15% for the subgroup of patients with concomitant p53-positivity and PTEN-negativity of tumors compared with DFS of 62% for others in 1 group (p53+PTEN+, p53-PTEN+, p53-PTEN-) at 100 months. The difference was highly significant (P = 0.006). FIGO stage (odds ratio = 8.0) and p53 PTEN status (odds ratio = 0.6) were predictive factors for tumor recurrences in a logistic regression and prognostic factors with hazard ratios (HRs) of 4.0 and 0.6, respectively, in a multivariate Cox regression analysis. In a separate Cox regression analysis, FIGO stage (HR = 3.6) and p53 status (HR = 2.0) were prognostic factors for DFS. For serous tumors (n = 51) recurrent disease was associated with FIGO stage (P = 0.013), and p53 loss (P = 0.029) but not with FIGO grade (P = 0.169). CONCLUSIONS: p53 status divides ovarian carcinomas into 2 subgroups after prognosis, also in serous tumors. Presence of PTEN in p53-positive tumors seems to protect from bad prognosis and absence of PTEN seems to worsen prognosis in early stages.

Prognostic impact of p53, p27, and C-MYC on clinicopathological features and outcome in early-stage (FIGO I-II) epithelial ovarian cancer.

INTRODUCTION: The objective of the study was to evaluate the prognostic effect of p53, p27, and C-MYC on clinicopathological features, recurrent disease, and disease-free survival (DFS) of 131 patients with ovarian cancer in International Federation of Gynecology and Obstetrics (FIGO) stages I-II. METHODS: The technique of tissue microarray and immunohistochemistry was used for detection of positivity/overexpression of the biological markers p53, p27, and C-MYC. RESULTS: In the complete series, the 5-year and overall survival rates were 68% and 71%, respectively. Positive staining for p53, p27, and C-MYC was detected in 25%, 57%, and 76% of cases, respectively. Positivity of p53, p27, concomitant p53-p27, C-MYC, and C-MYC-p27 status were associated with tumor grade. Positivity of p27 and concomitant p53-p27 were related to serous tumors. In survival analysis, DFS was related to p53, combined p53-p27, and combined p53-C-MYC status. Significant predictive factors for tumor recurrences were the FIGO stage (odds ratio [OR] = 9.8), status of node sampling (OR = 0.2), and p53 status (OR = 3.7) in a logistic regression analysis. In a multivariate Cox regression analysis, FIGO stage (hazard ratio [HR] = 4.3) and p53 status (HR = 3.0) were significant prognostic factors for DFS. In a separate Cox regression analysis, FIGO stage (HR = 2.0) and concomitant p53-p27-C-MYC status (HR = 0.3) were independent prognostic factors for DFS. It was possible to identify a subgroup, constituting 30% of the patients, who had excellent survival with tumors of concomitant p53 negativity, p27 positivity, and C-MYC positivity apart from the clinicopathological factors. Patients in this subgroup were longtime survivors with DFS of 92% at 5 and 9 years. CONCLUSIONS: The results of this study strongly suggest that patients with p53-positive tumors (alone/or combined with p27 and/or C-MYC) had significantly worse survival (DFS) compared with patients with p53-negative tumors. Patients with p53-positive tumors continued to have recurrences after the 5-year follow-up and die in disease.

Body mass index as a prognostic factor in epithelial ovarian cancer and correlation with clinico-pathological factors.

OBJECTIVE: To find out if body mass index (BMI) was associated with clinico-pathological features and prognosis in epithelial ovarian cancer (EOC). DESIGN: Retrospective cohort study. SETTING: Patients with EOC, who underwent primary surgery and postoperative chemotherapy in the Orebro Medical Region, Sweden, 1994-2003. SAMPLE: A total of 446 patients with stage I-IV EOC, who underwent primary surgery and chemotherapy with information of values of height and weight at the start of chemotherapy were eligible. METHODS: Patients were stratified by BMI according to guidelines set forth by the World Health Organization. Pearson's chi-squared test was used for univariate analyses. The level of statistical significance was p < 0.05. MAIN OUTCOME MEASURES: The survival curves were generated by using the Kaplan-Meier method, and in multivariate analyses the Cox regression model was used with cancer-specific survival as the end point. RESULTS. Of the patients, 5% were underweight (BMI < 18.5), 55% were of ideal body weight (BMI 18.5-25), 25% were overweight (BMI 25-30) and 15% were obese (BMI > 30). Among patients with serous tumors a significant (p = 0.01) worse survival was found in the subgroup of underweight (BMI < 18.5) patients compared with patients in the other BMI groups. In multivariate analysis only FIGO-stage and age were independent and significant prognostic factors. CONCLUSION: Overweight and obese patients did not have worse survival than normal weight and underweight patients. The prognostic impact of BMI on survival was only noted for underweight patients with serous tumors.

Borderline ovarian tumors in Sweden 1960-2005: trends in incidence and age at diagnosis compared to ovarian cancer.

The aim of the study was to investigate long-term trends in the incidence of borderline tumors and ovarian cancer in Sweden during 1960-2005, based on data from the population-based Swedish Cancer Register. We identified 6,288 patients with borderline ovarian tumors and a total of 34,977 cases of ovarian cancer during the study period. The age-standardized incidence of borderline ovarian tumors increased from 1.0 to 5.3 per 100,000 women-years from 1960-1964 to 2000-2005 and the incidence of ovarian cancer increased from 16.4 to 19.7 per 100,000 women-years from 1960-1964 to 1980-1989 and then declined to 16.6 per 100,000 women-years to the period 2000-2005. Borderline ovarian tumors comprised 15% of all primary ovarian neoplasms and the proportion increased from 8.3 to 23.6% during the study period. The median age at diagnosis for patients with borderline ovarian tumors and ovarian cancer was 55.2 and 61.6 years, respectively. In women younger than 40 years, 34% of all primary ovarian malignancies consisted of borderline ovarian tumors. For the 5 birth cohorts evaluated, the peaks of incidence occurred in stepwise younger age for each younger birth cohort for both borderline tumors and ovarian cancer. The increasing incidence of borderline ovarian tumors could be explained by an increase in diagnostic activity and by a lack of protective effect of oral contraceptive use. The decline in invasive tumors could be explained by a combination of factors, where the contribution of each is uncertain: shifting exposure to risk factors, a protective effect of oral contraceptive use, and increased detection of and removal of precancerous lesions.

Adjuvant chemotherapy with carboplatin and taxane compared with single drug carboplatin in early stage epithelial ovarian carcinoma.

The objective of the present study was to compare recurrence-free survival (RFS) in early stages (FIGO stages I-II) of epithelial ovarian cancer after adjuvant chemotherapy with carboplatin and a taxane (113 patients) and with carboplatin alone (27 patients). The distribution of clinical and pathological prognostic factors as well as type of primary surgery were comparable in the two groups. Recurrence rate was 21% and RFS was 79% in the series of patients treated with taxane-based chemotherapy and 19% and 81%, respectively, in the series of patients who received single drug carboplatin. Thus, no significant differences were recorded. The major toxicities in the present study were myelosuppression (46%) and neuro-toxicity (26%). Neuro-toxicity was more frequently (P=0.007) recorded and of higher grade (P=0.011) for patients in the carboplatin-taxane series compared with patients in the carboplatin series. RFS for patients in FIGO-stage I was 85% and for patients in FIGO-stage II only 47%. In a multivariate logistic regression analysis of predictive factors for tumor recurrence in the complete series (n=140) the FIGO stage was the only independent and significant (P=0.0006) predictive factor with an odds ratio of 6.4 (95% CI: 2.2-18.9) for stage II versus IA-C. Age, tumor grade and type of adjuvant chemotherapy (+/- taxane) were not significant predictive factors. In the present study, although based on a limited number of patients, we could not find any improvement in recurrence rate or recurrence-free survival for patients treated with a carboplatin-taxane combination regimen compared with patients treated with carboplatin monotherapy. The spectrum of side effects was also in favor of the monotherapy regimen. Further, larger randomized studies are needed to give a final and fully conclusive answer to this question.

Prognostic factors for surgical outcome and survival in 447 women treated for advanced (FIGO-stages III-IV) epithelial ovarian carcinoma.

The objectives of this population-based, retrospective study, was to find predictive factors for surgical outcome and long-term survival in 447 patients with epithelial ovarian cancer in FIGO-stages III-IV treated during 1975-1993. The median overall survival rate of this series was 18 months, the 5-year cancer-specific survival rate was 18%, and the 5-year overall survival rate, 16%. In a logistic regression analysis, type of surgeon was the strongest (P=0.006) predictive factor for surgical outcome after the age of the patient. The optimal debulking rate was 36% for gynecologic oncologists, 29% for general gynecologists, 24% for combined gynecologist and obstetrician with the third level of specialization, and 4% for general surgeons. Optimal debulking (no visible tumor or residual tumor <2 cm) was achieved in 26% of the cases. Predictive factors of the outcome of cytoreduction were FIGO-stage (P=0.007), histological subtype (P=0.016), and tumor grade (P=0.046) in univariate analyses. In a Cox multivariate analysis the most important prognostic factor for overall survival was the amount of residual cancer (P=0.000001) before age, grade and stage. Therefore, to achieve optimal surgical outcome and optimal overall survival rate the primary surgery of advanced ovarian cancer should be performed by gynecologic oncologists or by gynecologists specially trained in gynecologic cancer surgery.

Non-genital tract metastases to the ovaries presented as ovarian tumors in Sweden 1990-2003: occurrence, origin and survival compared to ovarian cancer.

OBJECTIVE: The aim of this register study was to determine occurrence of non-genital ovarian metastasis detected by gynecologic surgery presented as ovarian neoplasm in Sweden from 1 January 1990 to 31 December 2003. Origin of metastases and time of detection in relation to surgery were recorded. Age at diagnosis, survival for ovarian metastasis compared to ovarian cancer and prognostic factors were evaluated. METHODS: Utilizing the population-based Swedish In-Patient Registry, Cancer Registry and Causes of Death Registry, we identified 255 cases with non-genital tract metastases to the ovaries detected at gynecological surgery. During the study period, 10,955 newly diagnosed cases of ovarian cancer were reported to the Swedish Cancer Registry. RESULTS: The proportion of ovarian metastases detected at surgery of all ovarian neoplasm increased from 1.7% to 3.0% during the study period. The patients with ovarian metastasis of non-GI origin were younger than patients with primary ovarian cancer. The most common primary diseases were breast cancer (29%), colon cancer (27%) and gastric cancer (16%). Ovarian metastasis of GI origin preceded primary diagnosis in 51% of patients but for women with disease of non-GI origin the primary diagnosis was made in 18% of patients after surgery. Five-year survival for patients with ovarian metastasis of GI origin was 11% and it was 24% if metastases were of non-GI origin. Five-year survival for women with ovarian metastases from breast cancer was 26%. In a multivariate analysis, GI surgery at primary surgery for ovarian metastasis was unfavorable prognostic factor. Diagnosis of primary disease known before surgery, primary disease of non-GI or unknown origin and operation at university hospital all had favorable prognostic impact for overall survival. CONCLUSIONS: Detection of non-genital ovarian metastasis at gynecologic surgery is associated with poor prognosis, and prognosis is worse in tumors with GI origin and if the primary is not detected prior to surgery. The results indicate that a thorough patient evaluation is very important before surgery for suspected ovarian neoplasm.

Is adjuvant radiotherapy in early stages (FIGO I-II) of epithelial ovarian cancer a treatment of the past?

External abdomino-pelvic irradiation after primary surgery in early stages of epithelial ovarian carcinoma has been used as adjuvant therapy. The aims of this study were to evaluate efficacy and tolerability of abdomino-pelvic radiotherapy in ovarian carcinomas and to find predictive factors for recurrent disease. From January 1979 to December 1993, 215 patients with FIGO stage IA-IIC epithelial ovarian carcinoma were treated with postoperative radiotherapy. Whole-abdominal irradiation or lower abdomino-pelvic irradiation were used. The dose of specification was 20 Gy to the upper part of the abdominal cavity and 40 Gy to the lower part of the abdomen and the pelvic region. Primary cure was achieved in 210 patients (98%). During the period of follow-up, 79 tumor recurrences (38%) were recorded. Abdomino-pelvic metastases were most frequent (22%). The overall 5-year and 10-year survival rate for the complete series was 60 and 41%, respectively. In a multivariate analysis, FIGO-stage, histopathological type and tumor grade were independent prognostic factors with recurrent-free survival as the end-point. Among the histopathological subtypes, the highest survival rate (80%) was found for the subgroup of 24 patients with clear cell carcinomas. Early radiation reactions of any type were noted in 85% of the cases. The incidence of severe late bowel toxicity was 12% and, in 11 patients (5%), surgery was necessary due to late radiation complications of the intestine. In conclusion, adjuvant abdomino-pelvic radiotherapy is a treatment option in early stages of ovarian carcinoma together with chemotherapy. However, further studies are needed to find the subgroup of patients who specifically might benefit from radiotherapy in this setting.

Clinical and biological characteristics of clear cell carcinomas of the ovary in FIGO stages I-II.

Clear cell carcinoma of the ovary is considered to be a specific subtype among the epithelial ovarian malignancies. To characterize clear cell carcinomas in early FIGO stages (I-II) with regard to clinical and biological properties, a retrospective study was performed to compare these tumors with other histological subtypes. From a complete series of 226 patients with epithelial ovarian carcinomas in FIGO stages I-II, 28 patients with clear cell carcinomas were selected and the clinical and biological characteristics of these tumors were compared with the remaining non-clear cell carcinomas. All patients underwent primary staging laparotomy followed by adjuvant radiotherapy or chemotherapy. The apoptosis regulators p53, bcl-2 and bax, and the growth factor receptors EGFR and HER-2/neu were analyzed by immunohistochemical techniques and DNA analysis was performed by flow cytometry. Clear cell carcinomas stained negative for p53 significantly more often than other histological subtypes. Positive EGFR staining was seen more frequently in serous carcinomas than in the clear cell carcinomas. Aneuploid DNA status was seen more frequently in clear cell carcinomas than in other histological subtypes and tetraploid tumors made up 50% of the non-diploid tumors. Clear cell tumors were frequently (64%) found in FIGO stages IC and IIC and this was more common than for non-clear cell tumors. No difference was found in the rate of tumor recurrences or survival for patients with clear cell and non-clear cell carcinomas. Clear cell carcinomas of the ovary should be regarded as a separate entity among the epithelial ovarian carcinomas and they differ with regard to both clinical and biological characteristics when compared with non-clear cell tumors.