Prognostic Factors for Uterine Sarcoma and Carcinosarcoma: Insights from a 10-Year Follow-Up Study.

BACKGROUND Uterine sarcomas and carcinomas are rare tumors and treatment outcomes are far from expected. We investigated the prognostic significance of selected serum biomarkers and the impact of some clinical and tissue factors on overall survival (OS) at 10-year follow-up. MATERIAL AND METHODS The material for analysis was a group of 34 patients with uterine sarcomas and 18 with carcinomas. Immunohistochemistry was performed to determine Ki 67, p53 and ER and PR. Concentrations: CA 125, IL8, VEGF, SFTL1, VEGF R2, sTNFRI and MMP-9 were determined in the serum of patients before treatment and in the control group. RESULTS The most frequently elevated levels observed of sTNF RI in 94% and VEGF in 62%. On the ROC curve analysis, sTNF RI and VEGF concentrations showed the highest sensitivity. Patients with striated cell sarcoma, smooth cell sarcoma and high-grade rhabdomyosarcoma had the worst prognosis. Patient age, FIGO stage and expression of Ki67, p53, ER and PR, CA 125 (p<0.038) and IL-8 (p<0.024) were statistical prognostic factors for OS. However, in multivariate analysis, serum levels of: CA 125 concentration (p<0.045), age (p<0.010) and p53 expression (p<0.014) were found to be significant independent prognostic factors. CONCLUSIONS A 10-year follow-up of patients with uterine sarcoma indicates that age above 60 years at diagnosis and high p53 expression and elevated CA125 levels before treatment can be independent prognostic factors. The high diagnostic sensitivity of sTNF RI and VEGF suggests the possibility of using these biomarkers in the early diagnosis of uterine sarcomas.

Fertility-Sparing Management May Be Considered in Young Women with Uterine Sarcoma.

Uterine sarcomas occur very rarely in young women. Hysterectomy, which is a standard treatment, may not be acceptable for those patients, especially nulliparous women. Fertility-sparing management may be an alternative. The aim of the study was to assess fertility-sparing management in patients with uterine sarcoma. Eleven patients were eligible for the study. Histopathologic types of the tumor included: adenosarcoma (n = 3), low-grade endometrial stromal sarcoma (n = 3), low-grade myofibroblastic sarcoma (n = 1), leiomyosarcoma (n = 1), leiomyosarcoma myxoides (n = 1), rhabdomyosarcoma (n = 1), high grade endometrial stromal sarcoma (n = 1). The mean age of the patients at the time of diagnosis was 27.4 years (range: 17-35) and the average follow-up 61 months (range: 12-158). Six patients received adjuvant treatment: megestrol (n = 5) and chemotherapy (n = 1). Recurrence was diagnosed in five cases. Median time to recurrence was 35 months (range: 8-90). Three patients conceived spontaneously following treatment and gave at least one live birth. In total, five full-term pregnancies were recorded and five healthy children were born. Fertility-sparing management may be considered in some patients with uterine sarcoma; however, it may not be appropriate in high-grade endometrial stromal sarcoma. Patients with adenosarcoma may have a low chance of childbearing.

Overall survival (OS) in patients after chemotherapy for cervical cancer in Poland in years 2008-2015.

OBJECTIVES: To analyze cervical cancer prevalence as well as treatment methods, and its effects and assessment of overall survival of patients after chemotherapy for cervical cancer in Poland. MATERIAL AND METHODS: Data were collected from the registry of the National Health Fund (the only public payer in Poland). The data of patients treated in 2008-2015, who were shown to the payer with the diagnosis of malignant neoplasm of cervix (C53 according to the ICD-10 classification), were included in the analysis. The annual and eight-year prevalence rates were calculated. The overall survival was calculated for patients treated with chemotherapy. RESULTS: In the analyzed period (2008-2015), 83,100 women were diagnosed with C53, of which 33,300 (40%) were reported in the group of hospital treatment. The median age of patients was 59 years (58.8 ± 12.87). The highest prevalence rate was observed in 2008 (16.94 patients/100,000 inhabitants). The highest annual and period (2008-2015) prevalence rates patients per 100,000 inhabitants were observed in the Podlaskie (17.03 and 115.53 respectively) and Pomorskie (14.19 and 101.43 respectively) voivodeships and the lowest in Dolnoslaskie voivodeship (10.47 and 78.87 respectively) and Podkarpackie voivodeship (10.79 and 71.29 respectively). Mean survival time was 55.12 months and its median 45.46 months. Annual survival time was observed in 76.79% of patients, 2-year in 60.61%; 3-year in 53.08% and 5-year in 46.65%. CONCLUSIONS: In the years 2008-2015 in Poland, the incidence of cervical cancer was even 4 times higher than the EU average, and the mortality was as much as 70% higher than the average for EU countries.

Analysis of incidence and overall survival of patients with vulvar cancer in Poland in 2008-2016 - implications for cancer registries.

OBJECTIVES: To analyze the incidence and overall survival rate of patients with vulvar cancer in Poland, based on the reporting data from the National Health Fund. MATERIAL AND METHODS: The incidence of vulvar cancer in Poland in 2008-2016 (9-year follow-up period) by voivodship and the number of patients undergoing combined hospital treatment were analyzed. For the group of patients treated systemically, overall survival (OS) probability was calculated using the Kaplan-Meier estimation method. RESULTS: In the period 2008-2016 in Poland, the diagnosis of malignant neoplasm of the vulva (C51% group) was made in 29,702 patients. The mean annual prevalence rate per 100,000 inhabitants was 8.3 ± 1.2 for Poland. The largest numbers of patients were reported in Mazowieckie and Slaskie voivodeships and the lowest in Opolskie and Podlaskie voivodeships. The median overall survival of patients treated with the combined method in 2008-2016 in Poland was 64.7 months (95% Cl: 58.0-70.0). One-year survival rate was observed in 77.6% of patients, 2-year in 64.4%, 3-year in 58%, over 5 years - 54.22%. CONCLUSIONS: In the years 2008-2016 in Poland, based on the data reported to the National Health Fund, the incidence of vulvar cancer was 4 times higher than the statistics of the National Cancer Registry, the WHO or the USA, which indicates either substantive or reporting errors. In Poland, 54% of patients treated with the combined therapy survive over 5 years which is a much lower result compared to highly developed countries.

Molecular classification of endometrial carcinoma, is it the new era of precision medicine?

For many years endometrial cancer has been subdivided into oestrogen - dependent (type I) and oestrogen - independent (type II), according to classical Bokhman classification. Histopathological evaluation including type and grade of tumour, along with clinical factors have been considered as very important prognostic factors that impact treatment decision. However, histologically similar tumours may have different outcomes. Recent molecular findings and new histopathological parameters have given new concept on risk stratification. The Cancer Genome Atlas Research Network (TCGA) of tumours have brought new insights into endometrial cancer management. Four molecular subgroups have been described: POLE ultramutated (POLE mut), p53 mutant (p53abn), mismatch repair deficient (MMRd) and non-specific molecular profile (NSMP). This new subdivision has been recently introduced in the European risk stratification system.

Prognosis of the patients suffered from uterine carcinosarcoma from rural and urban areas.

OBJECTIVES: Uterine carcinosarcoma is a very aggressive neoplasm. Patients' median age at diagnosis ranges from 62 to 67 years. The aim of this study was to compare treatment results and prognostic factors for residents of urban and rural areas suffering from uterine carcinosarcoma. MATERIAL AND METHODS: Clinical outcomes of 58 uterine carcinosarcoma patients treated in one institution were assessed: 25 residents of rural and 33 of urban areas. All the patients were treated by using surgery followed by chemotherapy (48 pts) or radiotherapy (10 pts). Standard chemotherapy regimen comprised of paclitaxel 175 mg/m2 and carboplatin on day one at area under curve (AUC) six every 21 days. Radiotherapy was performed by combined treatment - tele and brachytherapy. External beam pelvic radiation therapy (EBRT) once a day, five days a week with a daily fraction size of 1.8 Gy over five weeks at cumulative dose 50.4 Gy was the first part of adjuvant treatment. High-dose-rate (HDR) brachytherapy at dose 22.5 Gy was the second part of radiotherapy. RESULTS: A strong correlation between tumor diameter and the presence of lymph node metastasis was observed. Tumor size greater then 4.5 cm correlated with presence of node involvement and this parameter was statistically significant (p = 0.015). There was no significant correlation between other analyzed clinical factors and overall survival. In the period 2004-2010 43.5% (10/23) and 50% (14/28) of rural and urban residents, respectively, died due to carcinosarcoma progression. CONCLUSIONS: Uterine carcinosarcoma patients in rural and urban areas seem to have similar outcomes.

Contemporary principles of diagnostic and therapeutic management in cervical and ovarian neuroendocrine tumors.

Enhancing knowledge about neuroendocrine neoplasms causes the need to improve management of these tumors. Although these tumors are rare in clinical practice, their biological diversity makes both diagnostics and therapy a challenge for contemporary oncology. The article discusses the latest developments in the diagnostic procedures and methods of treatment of the cervical and ovarian neuroendocrine tumors. Algorithms are presented to understand the differences in therapeutic management in these malignancies.

Retrospective analysis of the diagnostic effectiveness of the sentinel lymph node biopsy (SLNB) in vulvar cancer.

OBJECTIVES: Inguinal lymphadenectomy used in the treatment of vulvar cancer often results in complications, such as lymphoedema or abnormal wound healing. Aim of this study was assessment of the diagnostic effectiveness of the sentinel lymph node biopsy (SLNB) procedure in patients treated due to vulvar cancer. MATERIAL AND METHODS: Eighty-four patients diagnosed with squamous cell vulvar carcinoma (FIGO I-IV) underwent preoperative lymphoscintigraphy with technetium 99 to map sentinel lymph node. During surgery sentinel lymph nodes were identified and resected, followed by complete bilateral groin lymphadenectomy. RESULTS: Sentinel lymph nodes were mapped with lymphoscintigraphy and biopsied in 84.3% and 90.1% of patients, respectively. False negative predictive value (FNPV) was 9.1% and false negative rate (FNR) was recorded in 16.7% of cases. Patients in advanced stages (FIGO III and IV) had significantly lower rate of lymphatic mapping compared to those in stage I and II (OR = 0.148, p = 0.022). Detection of sentinel lymph node in lymphoscintigraphy for tumor grade 2 and 3 was nearly eight times lower than for grade 1 cancers, however without statistical significance (OR = 0.126, p = 0.058). CONCLUSIONS: The use of SLNB should be limited to vulvar cancer patients in early clinical stages.

Plasminogen Activator Inhibitor Type 1 in Blood at Onset of Chemotherapy Unfavorably Affects Survival in Primary Ovarian Cancer.

Plasminogen activator inhibitor type 1 (PAI-1) belongs to the family of the plasminogen activator system. PAI-1 stimulates fibrinolysis and also promotes tumor progression. The aim of this study was to evaluate the prognostic value of blood plasma PAI-1 content in patients with epithelial ovarian cancer who start the first-line chemotherapy. PAI-1 content was measured in the blood of 61 patients with epithelial ovarian cancer at onset of first-line chemotherapy. The patients were further stratified into the low PAI-1 group (≤20 ng/mL; 33 patients) and the high PAI-1 group (>20 ng/mL; 28 patients). We found that the greater plasma PAI-1 content was associated with a significantly lower probability of a 5-year-long survival compared to that when PAI-I content was lower (45.5% vs. 69.5%, respectively; p = 0.04). However, the risk of cancer recurrence within 5 years failed to differ appreciably. A multivariate analysis revealed that the lower PAI-1 plasma content was an independent factor of longer overall survival (death risk ratio of 0.36, 95%CI = 0.16-0.79; p < 0.01). We conclude that PAI-1 is yet another biomarker of survival in patients with ovarian cancer.

The assessment of overall survival (OS) after adjuvant chemotherapy for patients with malignant endometrial cancer in Poland.

OBJECTIVES: In 2013 malignant endometrial cancers have amounted to 7.3% of all cancers diagnosed among women in the report by the Polish National Cancer Registry Raw prevalence rate amounted to 28.7, whereas standardised prevalence rate 15.6 per 100 000 population. Among the causes of death, these cancers amounted to 3% and were ranked ninth on the list of the most common causes of oncologic mortality of women. In the year 2013 a total of 1243 women died of malignant endometrial cancers. A stable increase of malignant endometrial cancer incidence has been observed for 2 decades. Despite that fact, the increase of the mortality incidence is at a much lower level, which demonstrates the much higher effectiveness of the treatment of such cancers. The recording rate of the malignant endometrial cancer mortality amounts to 95%, so the presented absolute numbers are reliable. Examining the clinical stages of malignant endometrial cancers, we can establish that approx. 85% of them are diagnosed at stage I or II according to the FIGO classification. Patients with advanced stages of cancer represent less than 15%. MATERIAL AND METHODS: retrospective analysis of endometrial body cancer prevalence data for the entire population of Poland, assessment of malignant endometrial cancer prevalence in the years 2008-2015 and overall survival probability in the population of patients undergoing adjuvant chemotherapy. RESULTS: The number of patients with a diagnosed malignant endometrial cancer within the studied period in Poland remains on a stable level (2008 - 30.6 thousand patients, 2015 - 40.2 thousand patients). Among all listed patients with the indica-tion of C54 each year approx. 20% enters hospital treatment. System therapy with chemotherapy drugs was used in approx. 1-2% of patients treated in hospitals. The average age of the patients was 64.9 years, and the median age 65 years. The num-ber of observations was 2085, including 1088 censored observations. The average survival for the sample under study was 30.67 month (SD = ± 0.6); median survival time was 23.93 month. The number of censored observations was 1088 (52.16%). Probable survival of 1 year is achieved by 67.57% of patients, 2 years by 49.73%, 3 years by 40.68%, above 5 years 30.77%. CONCLUSIONS: The incidence of endometrial cancer in Poland in the years 2008-2015 continues to grow at 5% upward trend (in Europe 3.4-5.9). In Poland in 2012, crude incidence rate for cancer of the uterus was 29.8 and did not differ significantly from the results in countries such as Finland, Slovakia, Sweden, Belgium and Bulgaria. The overall survival after adjuvant chemotherapy for patients with malignant endometrial cancer in Poland shows considerable differences depending on the region of the country.

Results of optimal debulking surgery with bowel resection in patients with advanced ovarian cancer.

BACKGROUND: The surgical treatment of patients with advanced-stage ovarian cancer is based on maximal cytoreduction with widening the debulking on the extra-ovarian tissues and infiltrated organs. The purpose of the study was to assess the outcome after optimal cytoreduction with partial bowel resection and to find the risk factors of relapse. Another goal was the quantitative and qualitative assessment of intra- and postoperative complications in the studied group. METHODS: The analysis of debulking procedures with intestinal resection and postoperative period in 33 ovarian cancer patients, The International Federation of Gynecology and Obstetrics (FIGO) stages III and IV, was performed. RESULTS: The optimal cytoreduction defined as less than 1.0 cm residual disease was achieved in all patients including the following: 26 patients (78.8%) with no macroscopic residual disease, 4 patients (12.1%) with the largest residual tumor less than 0.5, and 3 patients (9.1%) with 0.5 cm to less than 1.0 cm residual disease. The rectosigmoid resection was the most common surgical procedure (n = 27). The risk of relapse was significantly higher in subjects who had the macroscopic residual tumor left during the primary operation (57.1 vs. 11.5%, P = 0.035). A primary bowel tumor size was another predictor of relapse. The maximum tumor diameter was significantly larger (14.9 ± 6.7 cm vs. 10.3 ± 4.7 cm, P = 0.047) in patients who developed the relapse. CONCLUSIONS: As presented in the article, our outcomes and other authors' observations indicate that debulking surgery with bowel resection in patients with advanced ovarian cancer brings good results. Complications connected with bowel surgery are to be accepted. The interesting thing is that a primary bowel tumor size was a predictor of relapse.

[Recurrent ovarian cancer--qualification and results of surgical treatment]. / Nawrotowy rak jajnika--kwalifikacja i wyniki leczenia operacyjnego.

INTRODUCTION: Complete tumor cytoreduction seems to be beneficial for platinum-sensitive women with recurrent ovarian cancer (ROC). Selection of patients who might have a chance for complete debulking constitutes a real challenge. Several predictive models defining a chance for complete cytoreduction and help in patient selection for surgery have been developed. OBJECTIVES: The aim of the study was to evaluate the effectiveness of selected models in one clinical center and the impact of complete resection on treatment outcome. MATERIAL AND METHODS: A total of 17 patients with ROC, diagnosed at least 6 months after first-line chemotherapy were recruited for the study. The inclusion criteria were based on the AGO-score (DESKTOP I trial). The group were retrospectively analyzed based on the predictive model International Collaborative Cohort Score (Tian- score). The end point was the percentage of complete cytoreduction. Also, postoperative complications and progression-free survival (PFS) were evaluated. RESULTS: Out of 17 patients who meet the criteria of the the AGO-score, complete debulking was achieved in 13 (76.47%) cases. Comparing the results of the Tian-score, 12 (100%) patients who were considered to be at 'low-risk of surgical failure' were debulked optimally In addition, complete debulking was achieved in 1 patient from the high-risk group. In all optimally operated patients, the number of changes detected during pre-operative imaging was ≤ 3. In 11 patients after complete cytoreduction there was another relapse. The median of PFS was 16 months. CONCLUSIONS: The applied predictive models have proven to be effective in selecting patients who will benefit from surgical treatment of ROC.

[Splenectomy as a part of debulking surgery in patients with advanced ovarian cancer]. / Splenektomia jako czesc operacji cytoredukcyjnej u pacjentek z zaawansowanym rakiem jajnika.

OBJECTIVES: The aim of the study was the assessment of perioperative complications in patients with advanced ovarian cancer who underwent splenectomy to achieve optimal debulking. MATERIAL AND METHODS: We analyzed eight debulking procedures with splenectomy and the postoperative period in ovarian cancer patients, FIGO stage III/B-IV. Preoperative diagnostics included multidetector computed tomography (MDCT) or diffusion-weighted echo-planar magnetic resonance (MR-DWI). The following factors were analyzed: size of the removed tumor, size of remains left, blood loss, packed red blood cell transfusion, quantity and reason for reoperations, pancreatic amylase concentrations in the drainage fluid, wound infection, fever over 38 degrees C, and length of hospitalization. RESULTS: Complete debulking was achieved in 8 patients, including 5 cases with no macroscopic residual lesions and 3 patients with lesion diameter of < 10 mm. Median operative time was 175 min. There was one case of reoperation caused by perforation of the stomach wall (histologically confirmed stress ulcer). Median blood loss was 1050 ml and the rate of packed red blood cells transfusion was 75%. Elevated amylase levels in the drainage fluid was noted in 6 patients. Amylase concentration was greater than 5 times the normal serum value during the first postoperative day. After postoperative day 3 it was lower than normal serum range. There were no cases of postoperative fever wound infections, or deaths. The length of hospitalization was 6 days. CONCLUSIONS: Splenectomy as a part of cytoreductive surgery for advanced ovarian cancer may contribute to achieving complete debulking and bring benefits, especially in cases with no macroscopic residual disease. The risk of intra- and postoperative complications related to splenectomy seems to be acceptable.

Uterine tumors resembling ovarian sex cord tumors, a clinicopathologic study of six cases.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) cause difficulties, both with respect to diagnosis as well as to the nomenclature. They belong to the group of low-grade malignant neoplasms, and their clinical course likely depends on the percentage of the sex cord-like component. Morphologically, they can be divided into type I and type II with less or more than 50% of sex cord-like areas, respectively. Six patients with an age range of 24 to 63 years underwent the treatment for primary UTROSCT at the Cancer Center and Institute of Oncology in Warsaw, Poland, between 2000 and 2011. In addition to the surgery, 4 patients were treated with gestagens. Biopsies or excisions from the tumors were examined microscopically and immunohistochemically. Two cases were classified as type I, and 4 cases, as type II tumors. The tumor size ranged from 3 to 24 cm. The sex cord component varied from 25% to 70%. By immunohistochemical examination, the sex cord-like component was calretinin positive, whereas the stromal component was positive for CD10 and negative for h-caldesmon in all the cases studied. In addition, progesterone receptor positivity was found in all the cases, and 4 tumors were positive for smooth muscle actin, cytokeratin AE1/3, and inhibin. No recurrences were noted in any of the 6 patients over 3 to 14.5 years of follow-up period. A correct subclassification of sarcomas of UTROSCT type is of crucial importance because most patients with this rare neoplasm respond well to gestagen therapy and have a good prognosis, compared with other uterine stromal sarcomas.

Differentiation of ovarian cancers from borderline ovarian tumors on the basis of evaluation of tumor vascularity in multi-row detector computed tomography--comparison with histopathology.

OBJECTIVE: The aim of this study was to evaluate the feasibility of multi-detector row computed tomography (MDCT) in the differentiation between borderline ovarian tumors and ovarian cancer on the basis of tumor morphology and specific features of tumor vascularity in correlation with the results at pathology. METHODS: A triphasic MDCT protocol was used for the analysis of tumor vascularity. The following features were taken into account: (1) The number of vessels in papillary projections, solid-tissue component, and septa (2 vs >2), (2) serpentine and chaotic configuration of vessels, (3) presence of microaneurysms, and (4) presence of arteriovenous microfistulas. Masses with at least 3 of 4 features were considered ovarian cancer (group A) and masses with 2 features or less as borderline tumor (group B). Radiological findings were compared with results of postoperative pathology. RESULTS: Pathologic vessels were found in all 56 patients. Thirty-two patients were included in group A and 24 in group B. The results of pathology were as follows: in group A: 31 malignant tumors, including 31 ovarian carcinomas and 1 benign cystadenoma; in group B: 22 borderline ovarian tumors, 1 benign cystadenoma, and 1 ovarian cancer. CONCLUSIONS: Morphological evaluation of tumor vascularity in MDCT seems to be an efficient method of differentiating between borderline ovarian tumors and ovarian carcinomas. Because of a small number of cases in the current study, a further research seems justified to confirm our results. The presented MDCT-angiographic criteria showed high sensitivity (97%) and specificity (96%) in differentiation of borderline ovarian tumors and ovarian cancers as compared with pathology. The presented CT-angiographic criteria of malignancy showed an excellent interobserver agreement.

microRNAs in uterine sarcomas and mixed epithelial-mesenchymal uterine tumors: a preliminary report.

Uterine sarcomas and mixed epithelial-mesenchymal uterine tumors are a heterogeneous group of rare tumors for which there are very few diagnostic markers available. As aberrant microRNA (miRNA) expression patterns represent putative diagnostic cancer markers, we aimed to identify miRNA expression profiles of the major uterine sarcoma subtypes and mixed epithelial-mesenchymal tumors of the uterus. Eighty-eight miRNAs were assessed by quantitative RT-PCR in cancerous and non-cancerous tissue samples collected from 29 patients with endometrial sarcoma, leiomyosarcoma, and mixed epithelial-mesenchymal tumors. Tumor and control samples significantly (P < 0.05) differed in the expression of miR-23b, miR-1, let-7f, and let-7c in endometrial sarcomas, and miR-1, let-7c, miR-133b, let-7b, miR-143, let-7a, let-7d, let-7e, let-7g, miR-222, let-7i, and miR-214 in mixed epithelial-mesenchymal tumors. All the significantly changed miRNAs were down-regulated in the malignant tissues as compared to their normal counterparts. This may suggest their tumor suppressor role in these malignancies. No statistically significant changes in miRNA expression levels were found between leiomyosarcoma tumors and controls. The identified miRNAs warrant further studies as valuable candidate markers for the differential diagnosis of uterine sarcomas from benign uterine lesions and between uterine sarcoma subtypes.

The promoter methylation and expression of the O6-methylguanine-DNA methyltransferase gene in uterine sarcoma and carcinosarcoma.

O6-methylguanine-DNA methyltransferase (MGMT) gene promoter hypermethylation is observed in a number of solid tumors and is correlated with the silencing of MGMT expression. In glioblastoma patients treated with the alkylating agent temozolomide, MGMT gene methylation status was shown to have predictive value in terms of prolonged overall survival. Recently, temozolomide has demonstrated promising activity in the treatment of soft tissue sarcomas, including those of the uterus. The tissue specimens involving tumor samples and normal uterine fragments were obtained from nine patients with smooth muscle uterine sarcoma, 11 with stromal uterine sarcoma and 17 with mixed uterine tumors. MGMT gene promoter methylation was analyzed by combined bisulfite restriction analysis (COBRA) while its expression levels were assessed using the real-time reverse transcription polymerase chain reaction (qRT-PCR). MGMT promoter methylation was observed in 27% of all tumor samples analyzed. When stratified by the disease type, 55.5% (5/9) of smooth muscle sarcomas, 23.5% (4/17) of mixed uterine tumor tissues and 9% (1/11) of stromal sarcomas showed MGMT methylation. The MGMT promoter methylation was associated with lower levels of gene expression in tumors when compared with those with an unmethylated promoter (P=0.0232) or normal tissues (P=0.0141). To conclude, MGMT promoter methylation and downregulation of gene expression is observed in a fraction of carcinosarcomas and non-epithelial malignant tumors of corpus uteri. The assessment of MGMT promoter methylation status may potentially identify patients who would benefit from temozolomide treatment.

[Smooth muscle tumor of uncertain malignant potential (STUMP)--clinico-pathomorphological analysis of the cases and literature review]. / Guz gladkomiesniowy o nieokreslonym potencjale zlosliwosci (STUMP)--analiza kliniczno-patomorfologiczna przypadków oraz przeglad pismiennictwa.

OBJECTIVES: This retrospective study was designed to evaluate the clinical and pathological features and outcomes of patients diagnosed with uterine smooth muscle tumor of uncertain malignant potential (STUMP). MATERIAL AND METHODS: Ten patients diagnosed with uterine STUMP and seen between 2008 and 2011 at the Memorial Cancer Center--Institute of Oncology in Warsaw were identified using the institution databases. Variables of interest included histopathological details, age at diagnosis, types of treatment and recurrence rate. RESULTS: The mean age at diagnosis was 41 years (range 25-56 years). The mean follow-up time was 16 months (range 4-29 months). Diameter of the tumors ranged from 3 to 29 cm. Uterine bleeding was the second most frequent symptom observed in this cohort In three cases conservative procedure was performed, whereas in other patients hysterectomy was performed. No recurrence was observed during the follow-up period. In all tumors mitoses were less than 10 per 10/hpf, atypia of middle or severe type, and in 3 cases necrosis was observed. In half of the tumors expression of TP53 was found, and value of MIB 1 was estimated at 2-35%. CONCLUSIONS: STUMP should be diagnosed by experienced pathologists due to the fact that they are often misdiagnosed as leiomyosarcomas. Clinical behavior of these tumors allows to consider a conservative management in patients wishing to preserve fertility

[Long-term outcome analysis in the treatment of granulosa cell tumors]. / Retrospeanaliza wyników leczenia ziarniszczaka jajnika.

INTRODUCTION: Granulosa cell tumors of the ovary (GCT) are derived from the sex cords and the ovarian stroma. Their natural history however is indolent with a very favorable long-term prognosis. Their extreme rarity represents a limitation in our understanding of their natural history management, and prognosis. MATERIAL AND METHODS: Retrospective analysis of patient documentation treated for GCT between 1988-2008 at the Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw, was performed. Clinical and pathological features of the study group, as well as methods and results of the treatment were analyzed. RESULTS: Medical documentation of 148 patients was analyzed. The majority of patients was classified as FIGO stage 1 (87.5%). Surgery was performed as primary treatment in all cases. Forty eight patients (32,6%) were held for observation stays, whereas 57.1% were qualified to receive adjuvant treatment: chemo- or radiotherapy. Mean progression free survival was 133.5 months (11.1 years) and was significantly longer in patients treated with the chemotherapy regimen when compared to radiotherapy (148 vs. 91 months respectively; p = 0.028). Overall survival was 173,7 months and was significantly longer in patients treated with adjuvant chemotherapy vs. RTH (165 vs. 121 months; p = 0.068). Recurrence of the disease was associated with poorer prognosis. CONCLUSIONS: GCTs are potentially curable neoplasms of the ovary with low treatment failure rates. Quick diagnosis and appropriate treatment in centers experienced in ovarian cancer surgery are the necessary conditions to obtain good results. The stage of the disease remains the most important prognostic factor chemotherapy with the use of bleomycine etoposide and cisplatin should be considered in patients who require adjuvant treatment.

Evaluation of selected ultrasonographic parameters and marker levels in the preoperative differentiation of borderline ovarian tumors and ovarian cancers.

OBJECTIVES: In young patients with borderline tumors the fertility-sparing treatment is indicated, thus the preoperative investigation is important. The aim of this study was to perform a comparative assessment of sensitivity and specificity of selected ultrasonographic and clinical parameters for the diagnoses of borderline tumors and ovarian cancers. METHODS: We retrospectively analyzed 57 patients who underwent surgical treatment in the Maria Sklodowska-Curie Memorial Cancer Center from Jan 01, 2008 to Dec 31, 2009. Ovarian cancers were diagnosed in 41 patients, and borderline ovarian tumors in 16 patients. Statistical model was developed to determine independent predictive factors that would be useful in preoperative differentiation between both tumors. The model included the following factors: menopausal status, tumor morphology, wall thickness (including outgrowths), septal thickness, echogenicity, resistive index, serum CA-125 level, and free fluid in the peritoneal cavity. RESULTS: Based on the statistical model developed, independent predictive factors in the differentiation between ovarian cancers and borderline tumors included the menopausal status (P=0.005), tumor echogenicity (P=0.047) and the presence of free fluid in the Douglas pouch (P=0.043). With the cutoff value of 13 (with scores below 13 indicating a borderline ovarian tumor, and scores of ≥13 indicating ovarian cancer), sensitivity was 90.2% and specificity was 87%. CONCLUSIONS: Our proposed model of preoperative evaluation has a sensitivity of 90% in the differentiation between ovarian cancers and borderline tumors. When combined with intraoperative findings, it allows optimal surgical therapeutic decisions to be made in patients with borderline ovarian tumors.