Malignant Ovarian Germ Cell Tumors Research Articles

[Clinical analysis of 12 cases of ovarian yolk sac tumor].

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 μg/L) were significantly higher than normal (<25 μg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

Malignant ovarian and testicular germ cell tumors: Common characteristics but different prognoses.

Both ovarian and testicular germ cell tumors (GCTs) arise from the primordial germ cell and share many similarities. Both malignancies affect mainly young patients, show remarkable responsiveness to cisplatin-based therapy, and have an excellent prognosis, which also highlights the importance of minimizing long-term side effects. However, certain differences can be noted: The spreading of the disease differs, and the staging system and treatment recommendations are dissimilar. Moreover, the prognosis for ovarian GCTs is significantly inferior to that for testicular cancer, as exemplified in this review comparing the survival in Swedish patients diagnosed with testicular (1995-2022) and ovarian (1990-2018) GCTs. The 5-year overall survival in ovarian GCTs was 85.2%, versus 98.2% for testicular GCTs. How can this be explained? One reason may be the difference in knowledge, experience, and evidence because the incidence rate of testicular cancer is more than 15 times that of ovarian GCTs. Given the rarity of the disease in women and the lack of established guidelines, a comprehensive understanding of the disease and treatment decisions is challenging. The main objective of this review is to derive insights from testicular GCTs (seminoma and non-seminoma) by reviewing etiological, tumor biological, and clinical knowledge, and to thereafter suggest actions for ovarian GCTs based on this. We hypothesize that by adopting specific treatment strategies from testicular GCTs-including de-escalating adjuvant chemotherapy for low-risk patients and implementing more standardized and intensive treatment protocols in cases of relapse-we can improve the prognosis and minimize long-term side effects in ovarian GCT patients.

Component Patterns and Survival Outcomes in Patients with Mixed Malignant Ovarian Germ Cell Tumors: A Retrospective Cohort Study

AimsTo evaluate the component patterns and risk stratification in patients with mixed malignant ovarian germ cell tumors (mMOGCT). MethodsA retrospective study of 70 mMOGCT patients treated in our hospital between 2000 and 2022 was conducted. The recurrence-free survival (RFS), disease-specific survival (DSS), and risk stratification systems based on scoring the identified prognostic factors were assessed. ResultsYolk sac tumor component was the most common type (80%), followed by dysgerminoma (50%), immature teratoma (40%), embryonic carcinoma (27.1%), and chorionic carcinoma (15.7%). The 5-year RFS and DSS rates were 77.9% and 87.9%, respectively. International federation of gynecology and obstetrics (FIGO) stage III-IV (RR 3.253, P = 0.029) and normalization of tumor marker (TM) ≤ 3 cycles of chemotherapy (RR 6.249, P = 0.017) were risk factors for RFS and DSS, respectively. Significant DSS (RR 8.268, P = 0.006) was also noted between patients who had normalized TM ≤ 4 and ≥5 cycles of chemotherapy. FIGO stages I–II and stages III–IV were scored as 0 and 2, respectively. AFP normalization ≤3, 4, and ≥5 cycles of chemotherapy were scored as 0, 1, and 4, respectively. A total score of 0, 1–2, and ≥3 stratified patients into low-risk (43 patients), intermediate-risk (13 patients), and high-risk groups (14 patients), respectively. Patients in three risk stratifications manifested significant differences in DSS (P = 0.010) but not in RFS (P > 0.05). ConclusionDistinct different component patterns existed among mMOGCT patients, and predicting survival outcomes in a universal model was challenging.

The role of surgeon specialty in management and survival of malignant ovarian germ cell tumors: A population-based study

ObjectivesThe aim of this study is to describe management and survival in adult patients with malignant ovarian germ cell tumors (MOGCT) undergoing surgery by general gynecologists (GG) versus gynecologic oncologists (GO). MethodsThis is a population-based retrospective cohort study, including patients (age ≥ 18 years old) with MOGCT identified in the provincial cancer registry of Ontario, (1996–2020). Baseline characteristics, surgical and chemotherapy treatment were compared between those with surgery by GG or GO. Cox proportional hazards (CPH) model was used to determine if surgeon specialty was associated with overall survival (OS). ResultsOverall, 363 patients were included. One-hundred and sixty (44%) underwent surgery by GO and 203 (56%) by GG. There were higher rates of stage II-IV in the GO group (27.5% vs 3.9%, p < 0.001, and higher proportion of chemotherapy (64.4% vs 37.4%, p < 0.0001).Five-year OS was 90% and 93% in the GO vs GG groups, respectively (p = 0.39). CPH model showed factors associated with increased risk of death were older age at diagnosis (HR 1.09, 95% CI 1.07–1.12) and chemotherapy (HR 3.12, 95% CI 1.44–6.75). Surgeon specialty was not independently associated with all-cause death (HR 1.04, 95% 0.51–2.15, p = 0.91). ConclusionsIn this group of MOGCT, 5-year OS was not significantly different between patients having surgery by GO compared to GG. Nevertheless, survival rates were lower than expected in the GG group despite their low-risk features. Further exploration is warranted regarding the reasons for this and whether patients with suspected MOGCT may benefit from early assessment by GO for optimal management.

Outcome of patients with stage I immature teratoma after surveillance or adjuvant chemotherapy.

Immature teratomas are rare malignant ovarian germ cell tumours, typically diagnosed in young women, where fertility-sparing surgery is the treatment of choice. The role of adjuvant chemotherapy in stage I disease remains controversial. We evaluated the impact of surveillance versus chemotherapy on the recurrence rate in stage I immature teratomas. We collected a single centre retrospective series of patients with stage I immature teratomas treated with fertility-sparing surgery at San Gerardo Hospital, Monza, Italy, between 1980 and 2019. Potential risk factors for recurrence were investigated by multivariate logistic regression. Of the 74 patients included, 12% (9/74) received chemotherapy, while 88% (65/74) underwent surveillance. Median follow-up was 188 months. No difference in recurrence was found in stage IA/IB and IC immature teratomas [10% (6/60) vs. 28.6% (4/14) (P=0.087)], grade 1, grade 2, and grade 3 [7.1% (2/28) vs. 14.3% (4/28) vs. 22.2% (4/18) (p=0.39)], and surveillance versus chemotherapy groups [13.9% (9/65) vs. 11.1% (1/9)) (p = 1.00)]. In univariate analysis, the postoperative approach had no impact on recurrence. The 5-year disease-free survival was 87% and 90% in the surveillance and chemotherapy groups, respectively; the overall survival was 100% in both cohorts. Our results support the feasibility of surveillance in stage I immature teratomas. Adjuvant chemotherapy may be reserved for relapses. However, the potential benefit of chemotherapy should be discussed, especially for high-risk tumours. Prospective series are warranted to confirm our findings. To date, no consensus has been reached regarding the role of adjuvant chemotherapy in stage I immature teratomas of the ovary. Some studies suggest that only surveillance is an acceptable choice. However, guidelines are not conclusive on this topic. No difference in terms of recurrence was observed between the surveillance and the adjuvant chemotherapy group. All patients who relapsed were successfully cured with no disease-related deaths. Adjuvant chemotherapy should be appropriately discussed with patients. However, it may be reserved for relapse according to our data.

Ovarian Yolk Sac Tumors: Is Fertility Preservation Possible?

Abstract Yolk sac tumors make up 14% to 20% of all malignant ovarian germ cell tumors. Serum alpha-fetoprotein (AFP) levels are elevated in a significant number of patients and are useful for monitoring the response to treatment and for post-treatment surveillance. Surgery is required for diagnosis, staging, and treatment. The first case is a 12-year-old girl presented with abdominal pain. The ultrasonography (US) showed a huge pelvic tumor. AFP level was high (1000 mg/ml). Right salpingo-oophorectomy and pelvic lymphadenectomy were done. Histopathology reported yolk sac tumor of ovary. She received 3 courses of bleomycin, etoposide, cisplatin (BEP). The second case is a 25-year-old G1AB1 presented with pelvic pain and distension. The US showed a huge pelvic tumor in the right abdominopelvic region. AFP level was high (1000 mg/ml). Right salpingo-oophorectomy, omentectomy, and appendectomy were done. Histopathology reported yolk sac tumor of ovary. The patient received four cycles of BEP protocol; AFP level decreased to 10 mg/ml after the four cycles of chemotherapy. The third case is a 21-year-old girl presented with abdominal pain. The US showed a huge pelvic tumor in the right adnexa. AFP level was high (8700 mg/ml). Right salpingo-oophorectomy and pelvic lymphadenectomy were done. Yolk sac tumor is rare in children and it could be cured usually. In this study, we described three patients with ovarian yolk sac tumors and their fertility preservation treatments.These cases has reminded that in young age with high AFP levels and rapidly growing ovarian mass, diagnosis of the yolk sac tumor has to be kept in mind.

Effectiveness and safety of nintedanib in prevention of pulmonary fibrosis induced by bleomycin in malignant ovarian germ cell tumour: study protocol for a randomised, double-blind, placebo-controlled trial

IntroductionBleomycin is a crucial and irreplaceable chemotherapy regimen for malignant ovarian germ cell tumours (MOGCTs) but its toxicities especially pulmonary fibrosis have limited the dose of treatment efficacy and decreased...

Excellent Outcomes in Children, Adolescents, and Young Adults with Ovarian Germ Cell Tumors Treated by Either Reduced- or Standard-Dose Bleomycin.

To investigate the outcomes of children, adolescents, and young adults (AYAs) with malignant ovarian germ cell tumors (MOGCTs), we analyzed the data of 61 patients aged ≤39 years diagnosed with MOGCT between 2006 and 2022. Among 59 patients who received chemotherapy after initial diagnosis, 57 received BEP (standard dose of bleomycin with 30 units per week, n = 13) or bEP (reduced dose of bleomycin with 15 units/m2 on day 1, n = 44). The 5-year overall survival (OS) and event-free survival (EFS) rates were 98.3% and 84.9%, respectively. Reduced bleomycin dose did not adversely affect survival. Normalization of tumor markers within 3 months after surgery was significantly associated with better EFS (p < 0.01). Of the 59 surviving patients, 8 experienced surgery-related menopause, while 49 demonstrated menstrual recovery. After completion of chemotherapy, there was no significant difference in pulmonary function regarding bleomycin dose, and no overt nephrotoxicity. Approximately 60% and 25% of survivors experienced peripheral neuropathy at the end of chemotherapy and after 1 year, respectively (p < 0.01). Children and AYAs with MOGCT have favorable survival rates with minimal long-term toxicity, which are not influenced by a reduced bleomycin dose. Rapid normalization of tumor markers is associated with improved outcomes.

Fertility outcomes following surgery and multiagent chemotherapy in malignant ovarian germ cell tumor survivors: a survey study

ObjectiveTo assess fertility outcomes in long-term survivors of malignant ovarian germ cell tumors treated with fertility-sparing surgery with or without additional chemotherapy.MethodsWomen diagnosed and treated for malignant ovarian germ cell...

Clinicopathological Features and Survival Trends of Non-Epithelial Ovarian Cancer: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database

Introduction: Owing to their low incidence, no reliable statistics about prognostication derived from large sample sizes have been reported of malignant ovarian germ cell tumors (MOGCTs) and sex cord-stromal tumors (SCSTs). The present study aimed to investigate the clinicopathological prognostic factors and the survival trends of MOGCTs and SCSTs. Materials and Methods: Patients with MOGCTs and SCSTs were recorded in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2000 and 2019. Clinical, demographic, and treatment characteristics were compared between groups of MOGCTs and SCSTs. Cox risk regression analysis and Kaplan-Meier survival curves were used to compare overall survival (OS) and cancer-specific survival (CSS) and to assess the prognostic factors. Results: Information about 2,506 patients with MOGCTs and 1,556 patients with SCSTs was extracted from the SEER database, respectively. Aged <40 years and single were more common in patients with MOGCTs than in those with SCSTs. The vast majority of patients with MOGCTs and SCSTs underwent surgery (98.1% vs. 94.5%; p < 0.001), and women with MOGCTs were more likely to receive chemotherapy than women with SCSTs (56.1% vs. 32.2%; p < 0.001). For both patients before and after propensity-score matching, the 5-year OS rates of patients with SCSTs were lower than those of patients with MOGCTs (p < 0.05). In multivariate Cox regression analysis, both age and surgery were independent predictors of OS in patients with MOGCTs and SCSTs. FIGO staging was an independent predictor of CSS in MOGCT patients. Tumor size and chemotherapy were also independent predictors of CSS in patients with SCSTs. Conclusion: Compared to patients with SCSTs, those with MOGCTs tended to be younger and had a higher OS and CSS. Adjuvant chemotherapy after surgery did not prolong OS and CSS in patients with SCSTs.

Critical elements in the operative management of pediatric malignant ovarian germ cell tumors

Performance of the appropriate operation is highly important to ensure that any patient with a suspected ovarian germ cell tumor receives optimal therapy that prioritizes cure while simultaneoulsy minimizing risk of short and long-term toxicities of treatment. The following critical elements of any operative procedure performed for a suspected pediatric or adolescent ovarian germ cell tumor are reviewed: 1. Complete resection of the tumor via ipsilateral oophorectomy while avoiding tumor rupture and spillage, and 2. Performance of complete intraperitoneal staging at the time of initial tumor resection.

Fertility-sparing approach to malignant ovarian germ cell tumors - Oncologic and obstetric outocome: A retrospective study.

To evaluate oncologic (such as disease-free and overall survival) and obstetric outcomes in patients diagnosed with malignant ovarian germ cell tumors (MOGCTs). Patients diagnosed with MOGCTs between March 2007 and February 2022 were evaluated and patients who underwent fertility sparing surgery were included in this retrospective study. The obstetric and oncologic outcomes were evaluated by collecting data up until the patient's last follow-up visit from the hospital records and patient files. The study was approved by Başkent University Institutional Review Board (KA23/124). Seventy FSS patients were included in this study. The median age of the patients was 22.5 years (range: 11-37). The median follow-up time was 92.0 months (10-189). Immature teratoma was the most common histological subtype (32.9%). Bilateral involvement was detected in only one patient with immature teratoma (1.4%). The 5-year DFS rates of immature teratoma, dysgerminoma, yolk sac, and mixed germ cell histologic types were 91.1%, 94.1%, 82.4%, and 88.9%, respectively (P: 0.716). The 5-year OS rates of the same histologic types were 95.7%, 100%, 88.2%, and 88.9%, respectively (P = 0.487). All patients (100%) had a regular menstrual cycle after the completion of adjuvant treatment. The mean time between the last chemotherapy and menstruation was 4.38 months. To date, a total of 34 patients tried to conceive after the completion of disease treatment. A total of 23 (67.6%) patients conceived, resulting in 27 live births in 22 (100%) patients. Fertility preservation should be the first treatment option in MOGCTs in young patients due to the unilateral involvement of the disease and its chemosensitive nature.

Systematic Review of the Survival Outcomes of Neoadjuvant Chemotherapy in Women with Malignant Ovarian Germ Cell Tumors.

Randomized clinical trials assessing the efficacy of neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer have predominantly included women with high-grade serous carcinomas. The response rate and oncological outcomes of NACT for malignant ovarian germ cell tumors (MOGCT) are poorly understood. This study aimed to examine the effects of NACT on women with MOGCT by conducting a systematic review of four public search engines. Fifteen studies were identified, and a further descriptive analysis was performed for 10 original articles. In those studies, most women were treated with a bleomycin, etoposide, and cisplatin regimen, and one to three cycles were used in most studies. Four studies comparing NACT and primary debulking surgery showed similar complete response rates (n = 2; pooled odds ratio [OR] 0.90, 95% confidence interval [CI] 0.15-5.27), comparable overall survival (n = 3; 87.0-100% versus 70.0-100%), disease-free survival (n = 3; 87.0-100% versus 70.0-100%), recurrence rate (n = 1; OR 3.50, 95%CI 0.38-32.50), and adverse events rate from chemotherapy between the groups. In conclusion, NACT may be considered for the management of MOGCT; however, possible candidates for NACT use and an ideal number of NACT cycles remain unknown. Further studies are warranted to validate the efficacy of NACT in advanced MOGCT patients.

Characterizing Lymphovascular Invasion in Pediatric and Adolescent Malignant Ovarian Nongerminomatous Germ Cell Tumors: A Report from the Children's Oncology Group

BackgroundLymphovascular invasion (LVI) has been identified as a poor prognostic factor for a variety of tumors; however, its significance in malignant ovarian germ cell tumors (MOGCT) in pediatric and adolescent patients is not well described. We aim to clarify the significance of LVI in the subset of patients with nongerminomatous MOGCT. MethodsRecords of patients 0–20 years of age with MOGCT enrolled on Children's Oncology Group study AGCT0132 were reviewed. Patients with documented presence or absence of LVI in either institutional or central review pathology reports were included. ResultsOf 130 patients with MOGCTs, 83 patients had of the presence or absence of LVI documented in their pathology report. 42/83 patients (50.6%) were found to have LVI present. The estimated odds of having LVI was higher in patients with stage II and III disease, 11 years and older and with the presence of choriocarcinoma. Event-free survival (EFS) and overall survival (OS) remained high in patients with LVI. Approximately 50% of patients with a documented LVI status in either institutional pathology report or central review were found to have LVI. ConclusionsThe presence of LVI was higher in tumors with adverse risk factors including higher stage and age greater than 11 years. While LVI was not associated with EFS or OS in the intermediate risk group, further work is necessary to determine the effect of LVI on long-term disease-free survival. We, therefore, recommend routinely incorporating LVI status into institutional pathology reports for pediatric and adolescent patients with MOGCT. Level of EvidenceIII.

Prognostic factors and clinic-pathologic characteristics of ovarian tumor with different histologic subtypes-a SEER database population study of 41,376 cases.

Ovarian cancer is considered the leading cause of cancer-related deaths among all gynecological malignancies and a significant reason for mortality in women. This cohort study aimed to explore the survival trends of malignant ovarian tumors (MOT), cancer antigen 125 (CA125) level, and clinicopathological prognostic factors of MOT by histological subtype. Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 41,411 MOT cases diagnosed between January 2005 and December 2014 were extracted. According to the histological classification of MOT, four categories were included: epithelial ovarian carcinoma (EOC), malignant ovarian germ cell tumors (MOGCTs), malignant ovarian sex cord-stromal tumors (MOSCSTs) and ovarian neuroendocrine tumors (ONTs). We analyzed disease-specific survival (DS) and overall survival (OS) among the four categories, and their histological subtypes. Kaplan-Meier method was used to estimate survival curves, and log-rank test was used to evaluate differences between curves. Univariate and multivariate Cox proportional hazards models were applied to evaluate the prognostic impact of MOT. Significant predictors related to improved OS were younger age, low grade, early FIGO stage and localized SEER stage, while positive/elevated CA125 level was a risk factor. For MOGCT and MOSCST, 3-, 5- and 10-year DS rate estimates were all >80%, followed by ONT around 70%. Malignant epithelial cancer showed low DS rate at 3-year (70.7%), 5-year (58.7%), and 10-year (47.3%). EOC patients had the worst outcome, whereas MOGCT cases had the most favorable survival. Positive/elevated CA125 level led to poor prognosis. Furthermore, younger age, low grade, early FIGO stage and localized SEER stage were significant predictors for improved OS.

Pitfalls of Ovarian Dysgerminoma

This is a narrative review based on published articles, using the following criteria: key words “ovarian dysgerminoma” and “MRI (Magnetic Resonance Imaging)”; PubMed access; full-length English articles since inception to May 2023; original studies and case reports/series. Exclusion criteria were ovarian tumors other than dysgerminomas, non-English papers, nonhuman studies, and reviews. Dysgerminomas are the most common ovarian malignant germ cell tumors, accounting for 1-2% of all primary ovarian neoplasms.

Premature ovarian insufficiency caused by the treatment of ovarian malignant mixed germ cell tumor: a case report

Background: Premature ovarian insufficiency (POI) will bring women early and long-term adverse consequences, including estrogen deficiency-related symptoms (hot flashes, sweating, decreased libido, insomnia, etc.) and significantly increases the risk of chronic diseases including Alzheimer's disease, cardiovascular disease and osteoporosis, along with increased risk of early death. More importantly, POI has greater harm to women’s fertility. Mostly the causes of POI are unknown. Most important are iatrogenic factors such as radiotherapy, chemotherapy and surgery, which increase the risk of POI.

Clinical Challenges in the Management of Malignant Ovarian Germ Cell Tumours.

Nonepithelial ovarian cancers (NEOC) are a group of rare malignancies, including germ cell tumours (GCT) and sex cord-stromal tumours (SCST), along with small-cell carcinomas and sarcomas. GCTs represent 2-5% of ovarian cancers, with a yearly incidence of 4:100,000, and they usually affect young women and adolescents. Precursory germ cells of the ovary form the basis of GCT. They are histologically classified into primitive GCT, teratomas, and monodermal and somatic-type tumours associated with dermoid cysts. A primitive GCT can be either a yolk sac tumour (YST), dysgerminoma, or mixed germ cell neoplasm. Teratomas are either mature (benign) or immature (malignant). Given that malignant GCTs occur rarely compared to epithelial ovarian tumours (EOC), greater focus is required in their diagnosis and treatment. In this article, we review the epidemiology, clinical manifestations, diagnosis, and molecular biology, along with the management and therapeutic challenges.

Expression of p16 Tumor Suppressor Protein in Malignant Ovarian Germ Cell Tumors; Immunohistochemical Study.

Malignant ovarian germ cell tumors represent small percentage of malignant ovarian neoplasms but they affect significantly young age group. To investigate the immunohistochemical expression of p16 tumor suppressor protein in malignant ovarian germ cell tumors. Twenty-two malignant ovarian germ cell tumors (five dysgerminoma, eight immature teratoma, and nine yolk sac tumors), twenty mature cystic teratoma tumors and twenty normal ovarian tissue were immunohistochemically stained with p16 monoclonal antibody. Ki67 immunohistochemical staining was done for malignant ovarian germ cell tumors to assess proliferation. We found that p16 tumor suppressor protein is overexpressed in all malignant ovarian germ cell tumors in both nuclear and cytoplasmic locations compared to control and to mature cystic teratoma (p-value <0.001). Cytoplasmic p16 expression was significantly correlated to Ki67 proliferation index in malignant ovarian germ cell tumors (p-value = 0.033, r = 0.445). Overexpression of p16 in malignant ovarian germ cell tumors denotes that dysfunction of the cyclin dependent kinase pathway is involved in tumorigenesis of malignant ovarian germ cell tumors.

Cancer Stem Cell Markers Are Differentially Expressed in Malignant Ovarian Germ Cell Tumors.

The objective of this study was to analyze the expression and potential clinical role of cancer stem cell (CSC) markers in malignant ovarian germ cell tumors (MOGCT). CD34, CD44, and SOX2 protein expression by immunohistochemistry was analyzed in 49 MOGCT from patients treated in Norway during the period 1980-2011. Expression was analyzed for association with tumor type and clinicopathologic parameters. Tumors were diagnosed as dysgerminoma (DG; n=15), immature teratoma (IT; n=15), yolk sac tumor (YST; n=12), embryonal carcinoma (n=2), and mixed MOGCT (n=5). Tumor cell CD34 expression was significantly more common in YST, whereas stromal expression was only seen in IT (both P <0.001). CD44 was infrequently expressed, most often focally, in tumor cells, particularly in YST ( P =0.026). CD44 was widely expressed in leukocytes, most prominently in DG. SOX2 was most frequently expressed in IT, with predominantly focal expression in some YST and uniform absence in DG ( P <0.001). Stromal CD34 ( P =0.012) and tumor cell SOX2 expression ( P =0.004) were negatively associated with the involvement of the ovarian surface, presumably due to the low incidence of this event in IT. No significant association was found between CSC marker expression and other clinicopathologic parameters, including age, laterality, tumor diameter, and FIGO stage. In conclusion, CSC markers are differentially expressed in various MOGCT types, suggesting differences in the regulation of cancer-related processes. Expression of CD34, CD44, and SOX2 does not appear to be associated with clinical parameters in this patient group.