Analiza wyników fałszywie ujemnych subiektywnej oceny ultrasonograficznej guzów jajnika

Objectives: Currently transvaginal ultrasonography is the most effective method for ovarian tumor malignancy prediction. The aim of the study was to estimate the risk of false negative results in subjective interpretation of the ultrasound examination of ovarian tumors according to menopausal status. Material and methods: 318 women (210 pre and 108 post menopause) with adnexal masses were diagnosed preoperatively between 2004 and 2010. Subjective assessment of tumor characteristics was conducted by experienced ultrasound examiner. Tumors were divided into groups of: “certainly benign” (n=84), “probably benign” (n=116), “uncertain” (n=61), “probably malignant” (n=47), and “certainly malignant” (n=10). The percentage of false negative results was calculated among the first two groups according to menopausal status. Results: There were 91 malignant and 227 benign adnexal masses diagnosed in histopathological evaluation. There was one false negative result of subjective interpretation of ultrasound findings in postmenopausal women – 1.6% (1/64). She was a 63-year-old woman with bilateral solid ovaries sized: 4.2x3.1cm and 4.6x2.5 cm in ultrasound evaluation, where serous adenocarcinoma was diagnosed. There were three false negative results in premenopausal women – 2.2% (3/136). The first was a 34-year-old woman with a cyst with the appearance of ground glass of 19 x11cm in size where endometrioid ovarian adenocarcinoma was diagnosed. The second woman was a 32-year-old with a bilocular cyst 8x4.5cm diagnosed with borderline mucinous tumor. The third patient was a 21-year-old woman with unilocular-solid cyst 4.2x3.2cm where histopathological examination revealed borderline serous tumor. Conclusions: Subjective ultrasound evaluation of adnexal masses has high specificity but even in the group of tumors considered benign in premenopausal as well as postmenopausal women malignancy can be found. This occurs slightly more often before menopause.Cel pracy: Obecnie ultrasonografia przezpochwowa jest najbardziej efektywną metodą prognozowania złośliwości nowotworów jajnika. Celem pracy była ocena ryzyka wystąpienia wyników fałszywie ujemnych subiektywnej interpretacji badania ultrasonograficznego pacjentek z guzami jajnika w świetle ich statusu menopauzalnego. Materiał i metody: Analizie poddano 318 kobiet (210 przed i 108 po menopauzie) z rozpoznanymi i leczonymi operacyjnie guzami jajnika w latach 2004 - 2010. Subiektywna ocena cech guza została wykonana przez doświadczonego ultrasonografistę. Guzy podzielono na grupy: „na pewno niezłośliwe” (n=84), „prawdopodobnie niezłośliwe” (n=116), „niepewne” (n=61), „prawdopodobnie złośliwe” (n=47) i „na pewno złośliwe” (n=10). Odsetek wyników fałszywie ujemnych oszacowano na podstawie dwóch pierwszych powyższych grup w zależności od statusu menopauzalnego badanych pacjentek. Wyniki: W wyniku badania histopatologicznego rozpoznano 91 złośliwych i 227 niezłośliwych guzów jajnika. Wykazano jeden wynik fałszywie ujemny subiektywnej oceny ultrasonograficznej w grupie kobiet po menopauzie - 1,6% (1/64). Pacjentka miała 63 lata, w ocenie ultrasonograficznej obustronnie lite jajniki wielkości: 4,2x3,1cm i 4,6x2,5 cm, u której rozpoznano gruczolakoraka surowiczego. Wykazano trzy wyniki fałszywie ujemne u kobiet przed menopauzą - 2,2% (3/136). Pierwsza pacjentka miała 34 lata, w usg zmianę sugerującą torbiel endometrialną, wielkości 19 x11cm, u której rozpoznano gruczolakoraka endometrialnego. Druga kobiet miała 32 lata, dwukomorową torbiel o wymiarach 8x4,5cm, u której rozpoznano guz śluzowy o granicznej złośliwości. Trzecia pacjentka miała 21 lat, torbiel jednokomorową 4,2x3,2cm z wyroślami endofitycznymi oraz w badaniu histopatologicznym guz surowiczy o granicznej złośliwości. Wnioski: Subiektywna ocena ultrasonograficzna guzów jajnika ma wysoką wartość prognostyczną, ale nawet w grupie nowotworów uznanych za „niezłośliwe” zarówno u kobiet przed jak i po menopauzie może zostać rozpoznany ostatecznie nowotwór złośliwy jajnika. Nieznacznie częściej sytuacja taka występuje u kobiet przed menopauzą

Cytoplasmic and membranous receptor-binding cancer antigens expressed on SiSo cells (RCAS1) immunoreactivity in epithelial ovarian cancer cells represent differing biological function of RCAS1

Introduction. Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a selective suppressor of the immune response that has been linked to the evasion of immune surveillance by cancer cells. However, the exact prognostic impact of RCAS1 on epithelial ovarian cancer (EOC) has not been fully elucidated. The main aim of our study was to evaluate the influence of RCAS1 immunoreactivity (RCAS1-Ir) in EOC cells and in tumor stroma cells on patient overall survival. We also focused on RCAS1-Ir and the structure of the tumor stroma. Material and methods. RCAS1-Ir was evaluated by means of immunohistochemistry in 67 patients with EOC. We distinguished cytoplasmic and membranous immunoreactivity patterns. Results. We found that high cytoplasmic RCAS1-Ir in cancer cells was associated with more than a two-time shortened period of overall survival. Membranous RCAS1-Ir in cancer cells, as well as in tumor stroma macrophages and fibroblasts, did not correlate with patient survival. RCAS1-Ir in the cytoplasm of cancer cells was positively correlated with the degree of tumor stroma infiltration by fibroblasts and macrophages, but not with RCAS1-Ir in these cells. On the other hand, membranous RCAS1-Ir in cancer cells was positively correlated with RCAS1-Ir in fibroblasts and macrophages, but not with their quantity. Conclusions. Due to their different impacts on patient prognosis and tumor stroma structure, it seems that cytoplasmic and membranous RCAS1-Ir in EOC cells may have different biological functions

High tumor cell vimentin expression indicates prolonged survival in patients with ovarian malignant tumors

Objectives: The main aims of the study were to investigate the expression of vimentin and its correlation with the overall survival (OS) of patients with malignant ovarian tumors, and the correlation between vimentin expression and tumor stroma characteristics. Material and methods: The study focused on 94 malignant ovarian tumors that had been collected from women who were treated in the Department of Gynecology and Oncology of the Lukaszczyk Oncological Center, Bydgoszcz, Poland. Vimentin expression was assessed in both the cancer cells (expression intensity and quantitative analysis) and the tumor stroma (expression intensity). Vimentin expression was analyzed according to both stromal cellularity and the clinicopatho- logical features of the disease. Results: Both high cancer cell vimentin expression intensity and high quantitative vimentin expression (up to and includ- ing 30% of cells) indicated a significantly prolonged OS. Low vimentin stromal expression was associated with prolonged OS, although the difference did not reach the level of significance. High tumor cell vimentin expression intensity was as- sociated with significantly higher vimentin stromal expression. High vimentin expression in the tumor stroma indicated a significantly higher cellularity of the tumor stroma. Vimentin expression in cancer cells and the tumor stroma were not dependent on the histopathological type, the tumor grade or the FIGO stageof the disease. Conclusions: High cancer cell vimentin expression is associated with an improved OS of patients with malignant ovar- ian tumors. The expression of vimentin in ovarian malignancies may influence the structure of the tumor stroma

The potential predictive value of serum sRCAS1 levels for overall survival in endometrial cancer

Objectives: The main aim of the study was to evaluate the impact of levels of serum soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) on the overall survival (OS) rates in patients with endometrial cancer. Furthermore, we analyzed sRCAS1 levels according to the clinicopathological characteristics of the disease.  Material and methods: The study group comprised 43 patients who were being treated for endometrial cancer. We included 10 low-risk, 20 intermediate-risk and 13 high-risk endometrial cancers using the criteria of the European Society for Medical Oncology (ESMO), the European Society for Radiotherapy & Oncology (ESTRO) and the European Society of Gynaecological Oncology (ESGO). Serum sRCAS1 levels were obtained before and after surgery. Serum sRCAS1 levels were assessed using the ELISA method.  Results: In our univariate analysis, both the pre- and post-surgery high sRCAS1 groups of patients with endometrial cancer indicated a shortened OS. However, in our multivariate analysis, when patients’ age and disease-related risk was taken into consideration, only the post-surgery sRCAS1 levels remained as independent prognostic factors of a poor OS. Pre-treatment serum sRCAS1 levels were statistically significantly higher than post-surgery sRCAS1 levels; however, the difference between pre- and post-surgery sRCAS1 levels did not influence the patients’ OS rate. Pre- and post-surgery sRCAS1 levels did not differ according to tumor grade, stage of the disease or the disease-related risk group.  Conclusions: High post-surgery serum sRCAS1 levels seem to be an independent indicator of shortened overall survival in patients with endometrial cancer.

Cechy ultrasonograficzne oraz poziom CA125 w hormonalnie czynnych guzach jajnika

Objectives: Subjective ultrasonographic assessment is currently considered to be the best method of differentiation between various types of ovarian tumors. The aim of the study was to evaluate selected ultrasonographic features and CA125 levels of hormonally active ovarian tumors. Material and methods: A total of 1135 women with ovarian tumors were diagnosed between 2006 and 2014 at the Division of Gynecologic Surgery, Poznan University of Medical Sciences. Within these tumors, there were 60 hormone-secreting ovarian tumors, including: 20 granulosa cell tumors, 28 fibrothecomas, 10 dysgerminomas, 2 struma ovarii, and 9 metastatic ovarian tumors. The tumors were evaluated by ultrasonography according to the International Ovarian Tumor Analysis group criteria. Additionally, we evaluated serum CA125 levels in all patients. Results: Granulosa cell tumors occurred most frequently as large unilocular-solid cysts, moderately to highly vascularized, with low-resistance vascularization. Dysgerminomas were predominantly large unilocular-solid cysts or purely solid tumors, with minimal to moderate low-resistance vascularization. Fibrothecomas were solid masses with minimal, high-resistance vascularization. Struma ovarii occurred as small, solid masses with abundant, highresistance vascularization. Metastatic ovarian tumors presented mainly as multilocular-solid tumors with strong, low-resistance vascularization. Papillary projections were most frequently observed in metastatic tumors and granulosa cell tumors in 56% and 50% of the cases respectively, although only half of granulosa cell tumors papillary projections exceeded 3 mm. Elevated CA125 levels were found only in metastatic ovarian tumors. Conclusions: Hormonally active ovarian tumors present several ultrasonographic features which may facilitate preoperative diagnosis.Cel pracy: Subiektywna ocena ultrasonograficzna jest obecnie uważana za najlepszą metodę różnicowania poszczególnych typów guzów jajników. Celem pracy była ocena wybranych cech ultrasonograficznych guzów oraz poziomu CA125 w surowicy u pacjentek z hormonalnie czynnymi guzami jajnika. Materiał i metody: Analizie poddano 1135 kobiet z rozpoznanymi guzami jajnika w latach 2006 do 2014, leczonych w Klinice Ginekologii Operacyjnej Uniwersytetu Medycznego w Poznaniu. Rozpoznano 60 hormonalnie czynnych guzów jajnika w tym: 20 ziarniszczaków, 28 włókniakootoczkowiaków, 10 rozrodczaków i 2 wola jajnikowe. Do badania włączono również 9 guzów przerzutowych jajnika. Guzy były oceniane w badaniu ultrasonograficznym według kryteriów grupy International Ovarian Tumor Analysis i w surowicy pacjentek zmierzono stężenie CA125. Wyniki: Ziarniszczaki występowały zazwyczaj jako jednokomorowe torbiele z elementem litym o umiarkowanym lub silnym niskooporowym unaczynieniu, włókniakootoczkowiaki najczęściej były dużymi guzami litymi, o minimalnym unaczynieniu o charakterze wysokooporowym. Rozrodczaki występowały z podobną częstością jako jednokomorowe torbiele lub lite guzy, z umiarkowanym lub silnym unaczynieniem o charakterze niskooporowym. Guzy przerzutowe przyjmowały najczęściej formę guza wielokomorowego z elementem litym. Wyrośla endofityczne były najczęściej obserwowane w guzach przerzutowych oraz ziarniszczakach, odpowiednio w 56% i 50% przypadków, aczkolwiek tylko połowa wyrośli endofitycznych ziarniszczaków była większa niż 3 mm. Podwyższony poziom CA125 występował tylko w przypadku guzów przerzutowych jajnika. Wnioski: Guzy jajnika hormonalnie czynne posiadają kilka cech ultrasonograficznych, które mogą ułatwiać diagnozę przedoperacyjną

Salinomycin – a breakthrough in the treatment of ovarian cancer?

It is believed that cancer stem cells are the primary cause of cancer chemotherapy resistance, metastasis and relapse. The cancer stem cells form a small population of cells present in the tumor (accounting for less than 2% of the tumor mass) and have properties which enable them to survive chemo- and radiotherapy. These cells have the ability to self-renew, do not undergo apoptosis, display overexpression of the ALDH1A1 enzyme and ABC genes which encode transport proteins, and furthermore make use of various signaling pathways (Wnt, Notch, Hedgehog). Cancer stem cells may be identified and isolated from the tumor based on the characteristic biomarkers (CD44+, CD133+, CD117+, BMi1, Oct-4, nestin). It has been demonstrated that salinomycin, an antibiotic obtained from Streptomyces albus, eliminates cancer stem cells, which are resistant to treatment with cytostatics. Salinomycin causes apoptosis of these cells through a number of mechanisms, including the disruption of the Na+/K+ ion balance in biological membranes, inhibition of the Wnt pathway and resistance to transporters, increase in the activity of caspases, activation of the MAPKp38 pathway and inhibition of the nuclear transcription factor NF-κB. Salinomycin has an effect on many types of cancer. It may turn out to be a breakthrough in the therapy of chemotherapy-resistant cancers

The expression of Platelet-derived Growth factor receptors (PDGFRs) and their correlation with overall survival of patients with ovarian cancer

Objectives: The main aim of the study was to investigate the expression of Platelet-Derived Growth Factor Receptors alpha (PDGFR-alpha) and beta (PDGFR-beta) in malignant and benign ovarian tumors. We performed an analysis of the correlation of PDGFRs expression and stage of the disease, tumor grade and histopathological type of epithelial ovarian cancer (EOC). Additionally, we evaluated patient prognosis according to PDGFR expression.  Material and methods: Our study group was composed of 52 samples of EOCs, 35 samples of benign ovarian tumors (BOTs), and 21 samples of unchanged ovaries (UOs). The samples were collected from patients who had been operated on in the Division of Gynecological Surgery of the Poznan University of Medical Sciences.  Results: PDGFR-alpha was found to be expressed more frequently in cancer cells of EOCs, when compared with tumor cells of BOTs and epithelium of UOs. On the other hand, PDGFR-alpha receptors were present less frequently in the stroma of EOCs, when compared with the stroma of BOTs and UOs. Comparing the studied groups, there were no statistically significant differences in the expression of PDGFR-beta. The expression of both PDGFRs was not related to the FIGO stage, grade or histopathological type of EOCs. The expression of the PDGFR-beta receptor in cancer cells was associated with an improved overall survival among patients with EOCs. Patient prognosis was not affected by either PDGFR-alpha expres- sion or by PDGFR-beta tumor stroma expression.  Conclusions: The expression of PDGFR-alpha is significantly different when comparing EOCs, BOTs and UOs. However, the prognosis of EOC only seems to be affected by PDGFR-beta expression in cancer cells.

Expression of B7–H4 in endometrial cancer and its impact on patients’ prognosis

Objectives: The aim of the study was to evaluate the B7–H4 expression in endometrial cancer cells and to investigate its relationship with patient prognosis and clinicopathological features of the disease. Material and methods: We performed a single-center, retrospective cohort study that included endometrial cancer patients treated between 2012 and 2019. B7–H4 expression in specimens obtained from 63 patients was examined by immunohistochemical staining. The evaluation of B7H4 immunoreactivity was assessed using Immunoreactivity Scoring (IRS) system. Results: B7–H4 reactivity was observed in all, except one, endometrial cancer patients (98%). Staining intensity: no reaction in one case, weak in 16 (24%) patients, moderate in 25 (37%), and strong in 22 (35%). Twenty-nine (46%) patients showed B7–H4 immunoreactivity in more than 60% of cells, while, in 18 (29%) cases and 16 (25%) patients, the percentages were 30–60% and < 30% respectively. Median IRS was 2 (range 0–6). We found a significantly worse overall survival (OS) rate for patients with high versus low B7–H4 IRS (p = 0.03), however, in multivariate analysis, the difference in patient survival was close to the significance level (p = 0.052). B7–H4 expression was not related to histopathological type of the tumor, tumor grade, lymph node metastases, or the FIGO stage of the disease. Conclusions: Our result suggests that B7–H4 expression might be a useful prognostic factor in endometrial cancer