Effect of tumor-infiltrating T-lymphocytes on the aggressiveness of epithelial ovarian tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5053-5053
Author(s):  
Ines Vasconcelos ◽  
Sven Olek ◽  
Katharina Gellhaus ◽  
Tim Schwachula ◽  
Ioana Braicu ◽  
...  

5053 Background: Borderline ovarian tumors (BOT) are a low-grade form of ovarian malignancy with significantly less aggressive behavior than epithelial ovarian cancer (EOC). Since there is neither convincing scientific evidence nor a marker capable of predicting BOT’s behavior, we analyzed the role of immune tolerance in differential disease outcome. EOC and BOT were chosen due to similar disease etiology, despite different disease courses. Increased numbers of T-cell subpopulations infiltrate malignant tumors, so we used epigenetic tests to determine the prevalence of regulatory T-cells (Treg) and overall-T-Lymphocytes (oTL) in EOC and BOT. Methods: The ovarian cancer samples were provided by the European multicentric OVCAD study. The BOT samples were obtained from Tumor Bank Ovarian Cancer at Charité Campus Virchow (Germany). Samples and clinical data were prospectively collected and documented using validated SOPs. DNA was bisulphite-converted and forwarded to methylation-specific RT-PCR for CD3 and FOXP3 loci. Results: We evaluated 90 high-grade EOC, 12 BOT with invasive implants and 25 non-invasive BOT samples. Higher oTL-values correlate with mortality (p=0.008) and recurrence (p<0.001), while higher Treg levels correlate with recurrence (p=0.028). Patients with non-invasive BOT have lower oTL (p=0.019) and Treg (p=0.0005) levels than patients with invasive BOT and EOC, while BOT (both invasive and non-invasive) patients have lower Treg-to-oTL ratios than EOC patients (p=0.0005). Finally, oTL levels associate with overall survival in EOC (p=0.042). Conclusions: We observed a strict correlation between tumor-type, Treg and oTL levels, as well as Treg-to-oTL ratio. This is in agreement with our hypothesis that disease aggressiveness is associated with the amount tumor-infiltrating lymphocytes and may provide the explanation for differing disease courses in EOC and BOT.

2021 ◽  
Vol 75 ◽  
pp. 292-296
Author(s):  
Patrycja Sosnowska-Sienkiewicz ◽  
Piotr Nogal ◽  
Dawid Gawron ◽  
Korneliusz Wójcik ◽  
Danuta Januszkiewicz-Lewandowska ◽  
...  

Background: The aim of this study was to evaluate the incidence and histological type of lesions affecting the ovaries and to analyze employed methods of invasive treatment. Materials&Methods: Medical records of patients who were treated surgically for ovarian tumors in the years 2015 -2019 were reviewed. The study group was comprised of 31 female patients. Results: During 5 years time, there were 31 girls in the age from 3 months to 17 years hospitalized in the department. The mean age was 11 years. Histopathological examination was performed in all of these cases. 12 patients were diagnosed with malignant lesion, 19 with benign lesion. The most commonly diagnosed malignant tumors were a dysgerminoma and a mixed germ cell tumor. In the group of benign lesions, the most frequent tumor type was mature teratoma. The first occurring symptom was abdominal pain. Some of the lesions were diagnosed accidentally during ultrasonography. The diagnostics was expanded depending on the size of the tumor, staging and clinical condition of the patient. All the patients were treated surgically, 16 of them underwent laparoscopic surgery. Torsion of the ovary or oviduct was observed in 3 cases. Chemotherapy was introduced in 8 cases as complementary treatment. Conclusions: The most commonly diagnosed tumor was mature teratoma. Ultrasonography is the most frequent method of the ovaries’ examination. Ovarian lesions are characterized by non-specific clinical symptoms, which is associated with prevalent incidental detection during ultrasonography.


2013 ◽  
Vol 3 (5) ◽  
pp. 397-402 ◽  
Author(s):  
D Ghartimagar ◽  
A Ghosh ◽  
G KC ◽  
S Ranabhat ◽  
OP Talwar

Background: Ovarian cancer accounts for 3% of all cancers in females. About 80% of these are benign, and they occur mostly in young women between 20 and 45 years. Borderline tumors occur at slightly older ages while incidence of malignant tumors increases with age, occurring predominantly in perimenopausal and postmenopausal women. About 190,000 new cases and 114,000 deaths from ovarian cancer are estimated to occur annually worldwide. The aim of the study was to fi nd the incidence of surface ovarian tumor in a tertiary referral centre. Materials and methods: This was a retrospective study carried out in the department of pathology, Manipal Teaching Hospital from January 2001 to December 2012. Specimens were received from the same and other hospitals. Records were retrieved from the departmental data bank and were analyzed. Results: : A total of 310 cases of ovarian tumors have been reported in the same period. Among them, 180 cases were of surface epithelial origin and out of which 24 cases had bilateral tumors. Benign tumors comprised of 148 cases, 6 were borderline and 44 were malignant. Among these, the commonest was serous cystadenoma (98 cases) and the least common was malignant Brenner (2 cases). Combined or mixed tumor was seen in 9 cases. Conclusion: : In our study surface epithelial tumors comprised 58% of all ovarian tumors. In both benign and malignant cases, serous tumor was the commonest followed by mucinous tumors. Journal of Pathology of Nepal (2013) Vol. 3, No.1, Issue 5, 397-402 DOI: http://dx.doi.org/10.3126/jpn.v3i5.7868


2017 ◽  
Vol 27 (2) ◽  
pp. 252-257
Author(s):  
Gloria Cordeiro Vidal ◽  
Sabrina Croce ◽  
Frédéric Guyon ◽  
Guillaume Babin ◽  
Denis Querleu

ObjectiveThe aim of this study was to document the need of including the perigastric area when performing omentectomy in patients with stage III to IV serous epithelial ovarian tumors.Patients and MethodsPatients undergoing omentectomy in the setting of surgery for advanced epithelial serous ovarian cancer between February and September 2015 were included. Patients with macroscopic involvement of the perigastric area, nonepithelial serous tumors, and recurrences of ovarian cancer were excluded. The perigastric area was isolated and comprehensively processed for pathological examination.ResultsTwenty-four patients were included. Six patients underwent primary debulking surgery, and 18 patients underwent an interval debulking surgery. The mean number of pathologic blocks in the perigastric area was 24 (range, 8–41). Microscopic involvement of the perigastric omentum area was found in 62.5% of the cases. One patient had a low-grade serous carcinoma, with microscopic involvement of the perigastric area. Among the 23 patients with a high-grade serous carcinoma, 10 (83%) of 12 patients with a gross involvement of the rest of the omentum had a microscopic involvement of the perigastric area. The presence of microscopic disease in the perigastric arcade was found in 4 (36.3%) of 11 patients with a macroscopically normal omentum.ConclusionsIn this study, evidence is given that total omentectomy including the perigastric area is a necessary component of complete cytoreductive surgery in advanced ovarian cancer, whatever the macroscopic appearance of the omentum.


2004 ◽  
Vol 11 (2) ◽  
pp. 315-321 ◽  
Author(s):  
I Rzepka-G√≥rska ◽  
A Chudecka-G≈Çaz ◽  
B Kosmowska

The aim of this work was to compare mean concentrations of gonadotropins in serum and fluid from malignant and benign ovarian tumors. We enrolled 126 patients diagnosed with malignant epithelial tumors (n=40), borderline epithelial tumors (n=14), benign cystadenomas (n=28) and simple cysts (n=44) of the ovary. Premenopausal and postmenopausal subgroups were formed in each group. The concentration of FSH and LH was measured in serum and tumor fluid and the serum/tumor fluid ratio was calculated. The results in each group were compared and the sensitivity, specificity, positive and negative predictive values were determined. Mean concentrations of both gonadotropins in ovarian cancer fluid were significantly higher than in the remaining groups (P ranged from <0.005 to <0.0001). Mean serum/fluid ratios were lowest in ovarian cancer (FSH=2.91, LH=4.19). Our findings support the hypothesis that gonadotropins are involved in ovarian carcinogenesis and suggest that gonadotropin serum/tumor fluid ratios could be of value in the differential diagnosis of functional and organic cysts of the ovary.


2021 ◽  
Vol 50 (1) ◽  
pp. 69-73
Author(s):  
A. A. Tsypurdeeva ◽  
A. F. Urmancheeva ◽  
D. R. Zeldovich ◽  
E. F. Kira

To study the possibilities of laparoscopy in diagnosis of malignant ovarian tumors 635 patients at different stages of the disease were examined. High informing characteristics make it possible to recommend laparoscopy as a method of improved diagnostics of tumors in smallpelvic with the aim of early revealingof malignant tumors, morphologic verification and evaluation of tumor extensiveness, diagnosis of preclinical recurrent tumors in case of diverse results of non-invasive monitoring methods.


Author(s):  
Diego Salas-Benito ◽  
Enrique Conde ◽  
Ibon Tamayo-Uria ◽  
Uxua Mancheño ◽  
Edurne Elizalde ◽  
...  

Abstract Background: Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) may benefit from the use of selective markers, such as programmed cell death protein 1 (PD-1), for tumor-specific T-cell enrichment, as well as predictive biomarkers that help identify those patients capable of rendering tumor-reactive TIL products. We have investigated this in ovarian cancer (OC) patients as candidate for TIL therapy implementation. Methods: PD-1- and PD-1+ CD8 TILs were isolated from resected ovarian tumors and, after polyclonal expansion, TIL products were tested against autologous tumor cells. Reactivity was assessed by IFNg production (ELISPOT) and upregulation of CD137. Baseline tumor samples were examined using flow cytometry, multiplexed quantitative immunofluorescence, Nanostring technology, for gene expression profile (GEP) analyses, as well as a next generation sequencing gene panel, for tumor mutational burden (TMB) calculation, to identify those features that distinguished patients with tumor-reactive and non-tumor-reactive TIL products.Results: Tumor-reactive TILs were detected in half of patients and were exclusively present in cells derived from the PD-1+ fraction. Flow-cytometric studies revealed that fresh tumors from patients rendering tumor-reactive TILs presented a significantly higher frequency of CD137+ cells within the PD1+CD8+ subset. Multiplexed immunofluorescence supported this finding, which was particularly striking in intraepithelial CD8 TILs. Baseline GEP analysis showed that patients rendering tumor-reactive TILs exhibited a significantly higher T-cell inflamed signature. Despite no correlation between TMB and GEP, both parameters stratified tumors, with patients with higher TMB and/or T-cell inflamed signature score rendering tumor-reactive TILs. Conclusion: We have demonstrated that PD-1 identifies autologous-tumor specific CD8 T cells infiltrating ovarian tumors and have uncovered predictive factors that identify OC patients who are likely to render tumor-reactive cells from PD-1+ TILs. These findings have important implications for improving the efficacy of TIL therapy in OC.


2021 ◽  
Author(s):  
Arturas Dobilas ◽  
Charlotte Thålin ◽  
Håkan Wallén ◽  
Christer Borgfeldt

Abstract Background Inflammation is a hallmark of cancer, and emerging light is being shed on the neutrophil release of nuclear chromatin, referred to as neutrophil extracellular traps (NETs) in cancer and cancer associated thrombosis. The NET-specific marker citrullinated histone H3 (H3Cit) has been found to be elevated in plasma from patients with malignancies, suggesting the potential of NET markers, such as H3Cit, as novel cancer biomarkers. Objective To determine the levels of plasma H3Cit in blood in women with adnexal masses. Subjects and Method s: Peripheral blood samples were obtained preoperatively from 199 patients admitted for primary surgery of adnexal masses 2015–2017. Patients were grouped according to tumor type and stage of cancer. Plasma levels of H3Cit-DNA, cell free DNA (cfDNA) and the clinically implemented tumor marker cancer antigen 125 (CA125) were determined with ELISA. Results Plasma levels of H3Cit-DNA and cfDNA were not elevated in women with borderline or malignant ovarian tumors compared with women with benign tumors. Increased plasma levels of CA125 were detected in borderline and ovarian cancer stage I and stage II-IV compared with benign ovarian tumor patients (ptrend<0.001). In Cox regression analysis high levels of Ca 125 dichotomized at 326 IU/ml (median) showed worse overall survival hazard ratio 1.9 (95 % C.I. 1.03–3.36; p = 0.038). No differences were found in the survival analyses in malignant ovarian tumors analyzing the cfDNA and H3Cit-DNA levels. Conclusion This study did not find any association nor prognostic association between the plasma levels of the NET marker H3Cit and ovarian cancer patients.


2004 ◽  
Vol 14 (1) ◽  
pp. 89-93 ◽  
Author(s):  
A. M. Makhlouf ◽  
M. M. Fathalla ◽  
M. A. Zakhary ◽  
M. H. Makarem

ObjectivesTo investigate the expression of sulfatides in the tissue homogenates of malignant ovarian tumors, benign ovarian tumors, and control tissues and to study the relation between this marker and other clinico-pathological criteria such as the tumor type, grade of differentiation, surgical stage and ovulatory years.DesignCross-sectional study.SettingDepartment of Obstetrics and Gynecology and Department of Biochemistry, Assuit university hospital.SubjectsForty-six patients had malignant ovarian tumors. Sixteen patients had benign ovarian neoplasm. Thirty patients, with normal ovaries, represented the control group.MethodsA sample of the tumor or from the normal ovary (the control group) was sent for histopathological and biochemical examination. Sulfatides were measured by a rapid and sensitive spectrophotometric method.ResultsThere was a significant rise in benign tumors [median and range 43 (38–53)], than in the control group, 21 (18–31), P-value = 0.000. In malignant tumors, the median value of sulfatides was significantly higher than in benign tumors [127 (71–193), P-value = 0.000]. Sulfatides were significantly higher in patients with more ovulatory years and tumors of advanced stages (stage III/IV) and poor differentiation.ConclusionsSulfatides may play a role in the pathogenesis of benign and malignant ovarian tumors. It may also predict advanced stages in patients who are apparently early stage. It is also a candidate to study of their association with response to chemotherapy.


Author(s):  
George Pados ◽  
Dimitrios Zouzoulas

Borderline ovarian tumors (BOTs) are a specific subgroup of ovarian tumors and are characterized by cell proliferation and nuclear atypia without invasion or stromal invasion. They are usually more present in younger people than the invasive ovarian cancer and are diagnosed at an early stage and thus have a better prognosis. Histologically, borderline tumors are divided into serous (50%), mucosal (46%), and mixed (4%). The serous tumors are bilateral in 30% of the cases and are accompanied by infiltrations outside the ovary in 35% of the cases. These infiltrations may be non-invasive or invasive depending on their microscopic appearance and may affect treatment. Surgery is the approach of choice, and laparoscopic surgery, with the undeniable advantages it offers today, is the “gold standard.” All the surgical steps required to properly treat borderline tumors, at both diagnostic and therapeutic levels, can be safely and successfully be applied laparoscopically. Manipulations during surgery should be limited, and biopsies for rapid biopsy should be done within an endoscopic bag.


2014 ◽  
Vol 24 (Supp 3) ◽  
pp. S9-S13 ◽  
Author(s):  
Charlie Gourley ◽  
John Farley ◽  
Diane M. Provencher ◽  
Sandro Pignata ◽  
Linda Mileshkin ◽  
...  

AbstractLow-grade serous ovarian cancer is a recently described histological subtype of ovarian cancer that is clinically and molecularly distinct from the 4 other main histological subtypes (high-grade serous, clear cell, endometrioid, and mucinous). In particular, it differs from high-grade serous ovarian cancer in that it presents at a much younger age, is more indolent, and is relatively chemoresistant. Very few clinical trials have been performed exclusively in this tumor type; and as such, specific data guiding optimal management are limited.


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