Role of inhibin B in detecting recurrence of granulosa cell tumors of the ovary in postmenopausal patients

IntroductionSeveral biomarkers have been proposed for the detection of recurrences in adult-type granulosa cell tumors of the ovary. Here we validate the value of inhibin B in detecting recurrences and investigate its role in guiding follow-up examinations and treatment strategies in postmenopausal patients with ovarian adult-type granulosa cell tumors.MethodsData from 140 patients with a diagnosis of adult-type granulosa cell tumor of the ovary referred to the European Institute of Oncology of Milan from January 1996 to March 2016 were retrospectively collected. Among these, we selected data from 47 postmenopausal women for whom serial inhibin B measurements and related imaging examinations were performed according to the follow-up program, with a total of 315 serum inhibin B samples, together with the corresponding clinical examination, and 180 imaging examinations, confirming the presence or absence of macroscopic disease.ResultsAt a cut-off of 7 pg/mL, inhibin B levels were significantly correlated with the presence/absence of disease (p<0.01), with a sensitivity of 98.8% (95% confidence interval (CI) 95.8% to 99.9%) and a specificity of 88.9% (95% CI 82.6% to 93.5%). Further, inhibin B was positively correlated with the size of the lesion, and levels were significantly higher in patients with larger lesions also at a cut-off size of 3 cm (total diameter). Logistic regression showed that 15.6 pg/mL, 44.6 pg/mL, and 73.6 pg/mL inhibin B corresponded to 25%, 50%, and 75% probability of having an abnormal computer tomography scan, respectively.ConclusionsOur results confirmed that inhibin B is a sensitive and specific marker for adult-type granulosa cell tumors of the ovary that may be used during follow-up for detection of recurrences. Moreover, it could guide clinicians in the decision regarding when to perform imaging, avoiding redundant interventional tests in the absence of clinical suspicion.

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The clinical utility of serum anti-Müllerian hormone in the follow-up of ovarian adult-type granulosa cell tumors-A comparative study with inhibin B

International Journal of Cancer ◽

10.1002/ijc.29532 ◽

2015 ◽

Vol 137 (7) ◽

pp. 1661-1671 ◽

Cited By ~ 29

Author(s):

Anniina Färkkilä ◽

Sanna Koskela ◽

Saara Bryk ◽

Henrik Alfthan ◽

Ralf Bützow ◽

...

Keyword(s):

Comparative Study ◽

Granulosa Cell ◽

Clinical Utility ◽

Inhibin B ◽

Adult Type ◽

Granulosa Cell Tumors

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Adult type granulosa cell tumor in adult testis: report of a case and review of the literature

Rare Tumors ◽

10.4081/rt.2011.e37 ◽

2011 ◽

Vol 3 (4) ◽

pp. 117-119 ◽

Cited By ~ 12

Author(s):

Zhao Song ◽

David J. Vaughn ◽

Zhanyong Bing

Keyword(s):

Alkaline Phosphatase ◽

Granulosa Cell ◽

Epithelial Membrane Antigen ◽

Granulosa Cell Tumor ◽

Cell Tumor ◽

Review Of The Literature ◽

Adult Type ◽

Adult Testis ◽

Granulosa Cell Tumors ◽

Hmb 45

Granulosa cell tumors can be classified into juvenile and adult types and more commonly occur in ovaries. Adult testicular granulosa cell tumors are extremely rare and only 29 cases of adult type have previously been reported. We report here a 28-year old Caucasian man with a left testicular adult type granulosa cell tumor. The tumor measured 2.6×2.6×2.5 cm and was mitotically active (10/10 HPF). Immunohistochemical stains showed the tumor diffusely positive for inhibin and vimentin, and negative for epithelial membrane antigen, cytokeratins, synaptophysin, HMB-45, OCT-4, placental-like alkaline phosphatase and lymphoid markers. The reported granulosa cell tumors in adult testis were briefly reviewed.

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FOXL2 Mutations in Granulosa Cell Tumors Occurring in Males

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2011-0355-oa ◽

2012 ◽

Vol 136 (7) ◽

pp. 825-828 ◽

Cited By ~ 27

Author(s):

Joema F. Lima ◽

Long Jin ◽

Ana Rose C. de Araujo ◽

Michele R. Erikson-Johnson ◽

Andre M. Oliveira ◽

...

Keyword(s):

Granulosa Cell ◽

Leydig Cell ◽

Granulosa Cell Tumor ◽

Cell Tumor ◽

Testicular Tumors ◽

Adult Type ◽

Male Adult ◽

Granulosa Cell Tumors ◽

Juvenile Granulosa Cell Tumor ◽

Leydig Cell Tumors

Context.—Granulosa cell tumors comprise less than 5% of ovarian tumors in women and are much rarer in men, with only about 20 cases reported, to our knowledge. Recently, a somatic mutation of FOXL2 was reported in virtually all adult-type granulosa cell tumors in women. Objective.—To investigate FOXL2 mutations in granulosa cell tumors occurring in males. Design.—Five cases of an adult-type granulosa cell tumor from males were selected from the files of the Mayo Clinic. Nine other testicular tumors (1 juvenile granulosa cell tumor, 5 Leydig cell tumors, and 3 Sertoli-Leydig cell tumors) were evaluated for comparison. Inhibin immunostain was performed in all cases. DNA was extracted from formalin-fixed, paraffin-embedded tissue, followed by polymerase chain reaction and direct sequencing of FOXL2. Results.—All 5 cases had classic histopathologic features of the adult-type granulosa cell tumor. Inhibin was diffusely positive in all cases. FOXL2 402C→G (C134W) was identified in 40% (2 of 5) of the male, adult-type granulosa cell tumors. Of the 2 tumors positive for the mutation, 1 occurred in the testis of a man, and the other one affected the abdominal ovaries of a phenotypically male patient. All other testicular tumors were negative for the mutation. Conclusions.—The FOXL2 402C→G (C134W) mutation is also present in adult-type granulosa cell tumors occurring in men, although in a smaller proportion when compared with the rates reported in women. FOXL2 mutational analysis can be a helpful in the diagnosis of granulosa cell tumors of the testis.

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A long-term follow-up study of 176 cases with adult-type ovarian granulosa cell tumors

Gynecologic Oncology ◽

10.1016/j.ygyno.2011.10.015 ◽

2012 ◽

Vol 124 (2) ◽

pp. 244-249 ◽

Cited By ~ 51

Author(s):

Hsu-Dong Sun ◽

Hao Lin ◽

Mei-Shan Jao ◽

Kung-Liahng Wang ◽

Wen-Shiung Liou ◽

...

Keyword(s):

Granulosa Cell ◽

Adult Type ◽

Follow Up Study ◽

Granulosa Cell Tumors ◽

Ovarian Granulosa Cell ◽

Long Term Follow Up

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Granulosa cell tumor of the ovary: a clinicopathological study of six cases

Journal of Pathology of Nepal ◽

10.3126/jpn.v1i2.5400 ◽

1970 ◽

Vol 1 (2) ◽

pp. 96-99 ◽

Cited By ~ 2

Author(s):

RC Adhikari ◽

A Jha ◽

G Shayami

Keyword(s):

Granulosa Cell ◽

Teaching Hospital ◽

Tumor Size ◽

Granulosa Cell Tumor ◽

Cell Tumor ◽

University Teaching ◽

Malignant Neoplasms ◽

Patient Profile ◽

Granulosa Cell Tumors

Background: Ovarian granulosa cell tumors are rare malignant neoplasms that originate from the sexcord stromal cells of the ovary. The study aims to collate data of all granulosa cell tumors diagnosed in Tribhuvan University Teaching Hospital over the last 3 years and to describe the incidence, patient profile, ultrasonographic and histopathologic findings in our local context. Materials and Methods: A total of 6 (5%) granulosa cell tumors, diagnosed in Tribhuvan University Teaching Hospital during the period from April 2008 to March 2011. The patient’s age, symptoms, radiological findings, type of surgery performed, tumor size and follow-up status were evaluated. Results: All 6 patients were diagnosed as adult granulosa cell tumor, three of which were postmenopausal (50%) and remaining there was premenopausal. The symptoms recorded were uterine bleeding, abdominal pain, distention and mass. Grossly, in 3 cases granulosa cell tumors were solid and firm, in 2 cases solid and cystic and 1 case is predominantly cystic. Histologically, variety of patterns including diffuse, trabecular, cords, tubular, nesting and Call-Exner bodies were found. Nuclear grooves were observed in all cases. Follow up on 2 patients revealed no evidence of recurrence. Conclusion: This study supports the view that most granulosa cell tumors are diagnosed in stage I and there is good correlation between radiological and gross findings in terms of tumor size and solid or cystic status. Keywords: Granulosa cell tumor; Ovary; Histopathological findings DOI: http://dx.doi.org/10.3126/jpn.v1i2.5400 JPN 2011; 1(2): 96-99

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An alternative miRISC targeting a coding mutation site in FOXL2 links to granulosa cell tumor

10.1101/2020.02.18.954487 ◽

2020 ◽

Author(s):

Eunkyoung Shin ◽

Hanyong Jin ◽

Dae-Shik Suh ◽

Yongyang Luo ◽

Hye-Jeong Ha ◽

...

Keyword(s):

Granulosa Cell ◽

Molecular Basis ◽

Granulosa Cell Tumor ◽

Cell Tumor ◽

Adult Type ◽

Mutation Site ◽

Selective Degradation ◽

Granulosa Cell Tumors ◽

Highly Correlated ◽

Mirna Targeting

ABSTRACTRecent evidence suggests that animal microRNAs (miRNAs) can target coding sequences (CDSs); however, the pathophysiological importance of such targeting remains unknown. Here, we show that a somatic heterozygous missense mutation (c.402C>G; p.C134W) in FOXL2, a feature shared by virtually all adult-type granulosa cell tumors (AGCTs), introduces a target site for miR-1236, which induces haploinsufficiency of the tumor-suppressor FOXL2. This miR-1236-mediated selective degradation of the variant FOXL2 mRNA is preferentially conducted by a distinct miRNA-loaded RNA-induced silencing complex (miRISC) directed by the Argonaute3 (AGO3) and DHX9 proteins. In both patients and mouse model of AGCT, the inversely regulated variant FOXL2 abundance with the miR-1236 levels was highly correlated with malignant features of AGCT. Our study provides a molecular basis for understanding the conserved FOXL2 CDS mutation-mediated etiology of AGCT, revealing the existence of a previously unidentified mechanism of miRNA-targeting disease-associated mutations in the CDS by forming a non-canonical miRISC.

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Adult Granulosa cell tumor: A small mass producing troublesome morbidity to a woman

Journal of Bahria University Medical and Dental College ◽

10.51985/jbumdc2018030 ◽

2018 ◽

Vol 08 (02) ◽

pp. 126-128

Author(s):

Khalida Nasreen ◽

Samreen Iqbal

Keyword(s):

Granulosa Cell ◽

Abdominal Mass ◽

Granulosa Cell Tumor ◽

Small Mass ◽

Cell Tumor ◽

Adult Type ◽

Granulosa Cell Tumors ◽

Large Size ◽

Present Case Study

Granulosa cell tumors are sex-cord stromal tumor ofovary, a rare neoplasmaccounting for approximately 3-5% of all ovarian malignancies. Hormone producing tumor, a total of 95% of all GCTs are adult type and of large size. A majority of women present with abdominal mass and diagnosis made on histopathology. While small size symptoms producing Granulosa cell tumors are rare and it’s a rare virilizing tumor of adolescents. Adult Granulosa cell tumor is a clinically and molecularly unique subtype of ovarian cancer. The present case study reports on a case of a small size Granulosa cell tumor producing postmenopausal bleeding in 56-year-old woman.

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Inhibin B in diagnosis and monitoring of granulosa-cell tumors of ovary

Modern Oncology ◽

10.26442/18151434.2020.2.200121 ◽

2020 ◽

Vol 22 (2) ◽

pp. 116-118

Author(s):

Nina V. Lyubimova ◽

Almaz M. Beishembaev ◽

Yurii S. Timofeev ◽

Kirill I. Zhordania ◽

Nikolai E. Kushlinskii

Keyword(s):

Blood Serum ◽

Granulosa Cell ◽

Biochemical Marker ◽

Analysis Data ◽

Inhibin B ◽

Biologically Active ◽

Enzyme Linked Immunosorbent Assay ◽

Adult Type ◽

Rare Type ◽

Granulosa Cell Tumors

Introduction. Granulosa cell tumors of ovary (GCTO) rare type of malignant ovarian neoplasms formed from granulosa cells of the follicles capable to produce biologically active substances, including inhibin B. The purpose of this study is evaluation of clinical significance of inhibin B analysis in blood serum of patients with adult type of GCTO primary disease, relapse and during remission after treatment. Materials and methods. The study included 134 patients with GCTO, 15 patients with benign ovarian tumors and 82 healthy women. Inhibin B was determined in blood serum with standard enzyme-linked immunosorbent assay Inhibin B Gen II ELISA (Beckman Coulter, USA) in the microplate format. Results. The analysis data indicates a high sensitivity of inhibin B in the diagnosis of primary GCTO (92.3%) and in relapse (92.7%) with a specificity 100%. An increase of inhibin B before the clinical manifestation of relapse (for 212 months) confirms its significance as an effective biochemical marker for GCTO monitoring. Conclusion. Inhibin B can be used as effective biochemical marker of primary and GCTO and its relapses.

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