A Prospective Study of Inhibin in Granulosa Cell Tumors of the Ovary

Jobling, Tom; Mamers, Pamela; Healy, David; MacLachlan, Vivien; Burger, Henry; Quinn, Michael J.; Rome, Robert M.; Day, Arthur J.

doi:10.1006/gyno.1994.1291

Cited by 106 publications

(49 citation statements)

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“…Human tissue samples Ovarian granulosa cell tumors and normal ovarian tissue were obtained initially for a study of serum inhibin levels in ovarian tumors 12,13 and subsequently for studies of the molecular pathogenesis of granulosa cell tumors. 5,[14][15][16][17][18][19] Normal ovarian tissue was obtained from premenopausal women who had undergone elective hysterectomy with oophorectomy for a range of conditions not associated with ovarian malignancy (Supplementary Table 1).…”

Section: Melbournementioning

confidence: 99%

The FOXL2 C134W mutation is characteristic of adult granulosa cell tumors of the ovary

et al. 2010

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Granulosa cell tumors of the ovary represent B5% of malignant ovarian cancers. It has recently been reported that 95-97% of adult granulosa cell tumors carry a unique somatic mutation in the FOXL2 gene. We undertook this study to verify the presence of the FOXL2 Cys134Trp mutation in two geographically independent cohorts of granulosa cell tumors and to examine the expression pattern of FOXL2 in these tumors. A total of 56 tumors with the histological diagnosis of adult granulosa cell tumor from two centers, Melbourne and Helsinki, were examined for the presence of the mutation using direct sequence analysis. Two granulosa cell tumor-derived cell lines, COV434 and KGN, three juvenile granulosa cell tumors and control tissues were also examined. The expression of the FOXL2 gene was determined using quantitative RT-PCR and/or immunohistochemistry. We found that 52 of the 56 adult granulosa cell tumors harbor the mutation, of which three were hemi/homozygous. Of the four cases with wild-type FOXL2 sequence, reappraisal suggests that three may have been misclassified at primary diagnosis. The KGN cells were heterozygous for the mutation, whereas the COV434 cells had a wildtype FOXL2 genotype. The expression levels of FOXL2 were similar across the adult granulosa cell tumors and the normal ovary controls; one mutation-negative granulosa cell tumor had high FOXL2 mRNA levels, whereas the COV434 cells and two of the three juvenile granulosa cell tumors lacked the expression of FOXL2. Our data provide confirmation of the frequent presence of the FOXL2 C134W mutation in adult granulosa cell tumors and demonstrate that the mutation is not associated with altered FOXL2 expression. The mutation analysis may be a useful tool to differentiate particularly between cell-rich diffuse granulosa cell tumors and mitotically active sex cord-stromal tumors. This unique FOXL2 mutation appears to be characteristic of adult granulosa cell tumors.

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Section: Melbournementioning

confidence: 99%

The FOXL2 C134W mutation is characteristic of adult granulosa cell tumors of the ovary

et al. 2010

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“…Pituitary secretion of FSH, but not LH, is suppressed by inhibin [2,23]. Inhibin is a gonadal glycoprotein hormone, and it is secreted by the granulosa cells of several species [6,9,10,16,19]. The inhibin dimer is composed of an α-subunit and one of two β-subunits.…”

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confidence: 99%

Localization of Inhibin .ALPHA.-, .BETA.A- and .BETA.B-Subunits and Aromatase in Ovarian Follicles with Granulosa Theca Cell Tumor (GTCT) in 6 Mares

Hoque

Derar

Senba

et al. 2003

The Journal of Veterinary Medical Science

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ABSTRACT. To clarify the morphological and immunohistochemical characteristics in mares with granulosa theca cell tumor (GTCT), the localization of inhibin subunits (α, βA, βB) and aromatase in the granulosa cell layers and theca layers in the ovarian follicles were determined by immunohistochemical staining. The follicles were obtained from the ovaries of 6 mares with GTCT and 4 normal mares as controls. Immunohistochemically, inhibin α-subunit was localized in the granulosa cells of all follicles showing different sizes in all GTCT cases and βA-subunit was localized in two GTCT cases in all sized follicles. But inhibin βB-subunit and aromatase were not localized in GTCT cases. On the other hand, inhibin α-, βA-, and βB-subunits and aromatase were localized in the large and medium sized follicles, but inhibin βA-and βB-subunits and aromatase were not stained in the small sized follicles in normal cases. These findings suggest that some mares with GTCT can secrete dimeric inhibin (inhibin A), but all GTCT cases cannot secrete inhibin B. By the results of aromatase staining it is clear that testosterone is not converted into estradiol due to the lack of aromatase in the GTCT follicles.

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“…Jobling et al has shown more detailed survey of the usefulness of Inhibin measurements in the follow-up of 27 patients with granulose cell tumours, which was subsequently confirmed by Boggess et al and Petraglia et al 14 Healy et al showed that serum total Inhibin was also elevated in 70% of mucinous epithelial cancers, but much less frequently in serous and endometrioid subtypes of ovarian epithelial carcinoma. 15 In the present study, combined CA125 and serum Inhibin was found to be raised in 70% of benign and 100% of malignant cases.…”

Section: Discussionmentioning

confidence: 85%

Combined use of CA 125 and Inhibin as tumor marker for detection of ovarian cancer in comparison to CA 125 or Inhibin alone

Dubbewar¹,

Pathak²,

Biswas³

et al. 2017

Int J Reprod Contracept Obstet Gynecol

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Background: Ovarian cancers are diagnosed at an advanced stage. Early diagnosis is the key to reduce death from ovarian cancer. The present study is an effort to assess the suitability of combined test using CA 125 and Inhibin for early diagnosis of ovarian cancer as compared to CA125 or Inhibin alone.Methods: Fifty women with clinical suspicion of ovarian malignancy attending Gynae OPD were enrolled. All of these women were subjected to estimation of CA 125 and Inhibin levels prior to surgical intervention. A value of 35 IU/ml was taken as positive for CA 125. For Inhibin, 10.5 pg/ml was taken as cut off for premenopausal patients, whereas, any detectable assays were taken as positive for postmenopausal patients. The results were analyzed after establishing final histopathology of the disease.Results: Out of 50 patients recruited, 30 (60%) were found to have carcinoma ovary and 20 (40%) were found to have benign diseases. Out of 30 cases of carcinoma ovary, CA125 was raised in 81% of cases and Inhibin was raised in 78% of cases. For detection of carcinoma ovary, CA 125 was found to have a sensitivity of 90% and specificity of 60% with a positive predictive value of 77% and negative predictive value of 80% which were statistically significant. Sensitivity and specificity of serum Inhibin for the same was 86.6% and 20% respectively. The positive and negative predictive value were 61.9% and 50%, which were not statistically significant. Sensitivity and specificity of combined CA125 and Inhibin were 100% and 30% respectively. The positive and negative predictive value were 68.1% and 100% respectively, which were statistically significant.Conclusions: Combined use of CA125 and Inhibin has got better sensitivity and specificity in detection of ovarian cancer in comparison to CA 125 or Inhibin used alone.

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A Prospective Study of Inhibin in Granulosa Cell Tumors of the Ovary

Cited by 106 publications

References 0 publications

The FOXL2 C134W mutation is characteristic of adult granulosa cell tumors of the ovary

The FOXL2 C134W mutation is characteristic of adult granulosa cell tumors of the ovary

Localization of Inhibin .ALPHA.-, .BETA.A- and .BETA.B-Subunits and Aromatase in Ovarian Follicles with Granulosa Theca Cell Tumor (GTCT) in 6 Mares

Combined use of CA 125 and Inhibin as tumor marker for detection of ovarian cancer in comparison to CA 125 or Inhibin alone

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