Ovarian Granulosa Cell Tumors in Childhood

Merras‐Salmio, Laura; Vettenranta, Kim; Möttönen, Merja; Heikinheimo, Markku

doi:10.1080/088800102753541297

Cited by 61 publications

(61 citation statements)

References 41 publications

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“…GCTs are also highly vascularized and hemorrhagic and may present as large abdominal masses with acute abdominal pain (1). The median age of diagnosis in the adult subtype of GCT is 50-54 years, while the more uncommon juvenile subtype (5%) is diagnosed in children and adolescents (3,4). Generally, GCTs are diagnosed at an early stage and are considered to have relatively good prognosis with more than 90% 5-year survival rate (1).…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Färkkilä¹,

Anttonen²,

Pociuviene³

et al. 2011

European Journal of Endocrinology

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Objective: Ovarian granulosa cell tumors (GCTs) are hormonally active sex cord stromal tumors accounting for 3-5% of all ovarian cancers. These tumors are generally diagnosed at an early stage but there is a high risk of recurrence, associated with high mortality. Treatment of recurrent GCTs is difficult, and biologically targeted treatment modalities are lacking. GCTs are highly vascularized, and angiogenic factors most probably play a role in their pathology. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis, but in GCTs, the role of VEGF and its receptors VEGFR-1 (FLT1) and VEGFR-2 (KDR) remains largely unknown. Our objective is to study the expression of VEGF and its receptors in human GCTs. Methods: We analyzed GCTs from 106 patients for the expressions of VEGF and its receptors utilizing tumor tissue microarray, tumor mRNA, and patient serum samples. Results: We found that VEGF and its main biologically active receptor VEGFR-2 were highly expressed in primary and recurrent GCTs, when compared with normal granulosa-lutein cells. The expression of VEGF correlated positively to tumor microvessel density and to VEGFR-2 expression at the protein (P!0.05) and mRNA (P!0.05) levels. In contrast to VEGFR-2, the expression of VEGFR-1 was weak. Tumor VEGF protein expression was not prognostic for recurrence, however, we found high levels of circulating VEGF in the serum of patients with primary GCT. Conclusions:The results suggest an important role of VEGF and VEGFR-2 in GCT pathology and support the possibility of applying novel VEGF-or VEGFR-2-targeted treatments to patients with GCT.

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Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Färkkilä¹,

Anttonen²,

Pociuviene³

et al. 2011

European Journal of Endocrinology

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“…Although hyperandrogenism in granulosa cell tumors of the ovary has been reported by several investigators [1,7,8,18,19,20,21,22], its pathophysiology has not been elucidated so far. We recently showed that low or absent expression of SOX9 along with aberrant expression of FOXL2 in granulosa cell tumors of the testis could be associated with a transdifferentiation of tumoral cells from male to female type [9].…”

Section: Discussionmentioning

confidence: 99%

“…Other less frequent tumors in this class are thecoma fibromas, Sertoli cell tumors, sex cord tumors with annular tubules, and gynandroblastomas [1]. Ovarian granulosa cell tumors are further divided into two subgroups: juvenile and adult tumors.…”

Section: Introductionmentioning

confidence: 99%

Unusual Virilization in Girls with Juvenile Granulosa Cell Tumors of the Ovary Is Related to Intratumoral Aromatase Deficiency

Kalfa¹,

Meduri

Philibert³

et al. 2010

Horm Res Paediatr

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Background: Hyperandrogenism is a rare symptom of juvenile ovarian granulosa cell- tumors (JGCTO). This study aimed to determine whether hyperandrogenism was related to overexpression of SOX9, decreased expression of FOXL2 or absent aromatase expression in tumor with particular scheme of expression of P450scc and P450c17α. Methods: Through a nationwide study including the French Society of Pediatric Oncology, 6/30 patients with JGCTO presented with clinical hyperandrogenism and high plasma testosterone. Tumor specimens underwent immunofluorescence (SOX9, FOXL2) and immunochemistry (aromatase, P450scc, P450c17α). Results were compared with patients without hyperandrogenism. Results: SOX9 was expressed in the granulosa cell nucleus in 2/6 cases but also in 9/24 tumors without hyperandrogenism (p = n.s.). FOXL2 was absent or decreased in 3/6 cases of JGCTO with hyperandrogenism with no statistical difference from the group without this symptom. In 6/6 patients, the intratumoral expression of aromatase was absent (n = 5) or dramatically reduced (n = 1). In contrast, 15/24 patients without virilization exhibited conserved aromatase expression in their tumor (p < 0.05). A variable number of tumoral cells expressed P450scc while some interstitial cells were focally immunopositive for P450c17α. Conclusion: Unusual virilization in girls with JGCTO is not explained by a dysregulation in SOX9 or FOXL2 expression, but is related to a localized defect of aromatase expression in granulosa cells and to the ability of interstitial cells to produce testosterone.

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“…Ascites in 10% of them is reported [4]. This tumor can present in divers ages from infancy to teenage but it mostly presents in the age of 8 or 9 years old [5].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Cause of Precocious Puberty in an 8-Year-Old Girl Ended up in Juvenile Granulosa and Theca Cell Tumor of the Ovary

Ordooei¹,

Karimi-Zarchi²,

Malekzadeh³

et al. 2013

JCT

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Isosexual precocious puberty in girls has several etiologies. Juvenile granulose cell tumor is one of the rarest causes that only stands for 1.5% of ovarian cancers. This tumor mostly encounters in first 2 decades of life. This paper is a report of an 8-year-old girl with precocious puberty that within five months developed breast enlargement followed by menarche. Works which are done to find the underlying cause of precocious puberty revealed juvenile granulosa cell tumor in her left ovary. She then under went laparoscopic surgery and 3 courses of chemotherapy. She did not experience any vaginal bleeding after that and the serum level of estradiol lay among its normal ranges, but after that the tumor relapsed and presented as abdominal pain and a huge mass which under went resection of all afflicted tissues. After 2 courses of chemotherapy, her status deteriorated and unfortunately she died after 6 months from the time of diagnosis. Treatment for this disease is consists of resection surgery and chemotherapy. If this tumor is diagnosed in its early stages, it will be curable, but in its advanced stages, up to 80% of patients die from recurrent tumors. The reported patient was diagnosed at stage IIIC that had poor prognosis.

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Ovarian Granulosa Cell Tumors in Childhood

Cited by 61 publications

References 41 publications

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Unusual Virilization in Girls with Juvenile Granulosa Cell Tumors of the Ovary Is Related to Intratumoral Aromatase Deficiency

Investigation of the Cause of Precocious Puberty in an 8-Year-Old Girl Ended up in Juvenile Granulosa and Theca Cell Tumor of the Ovary

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