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Nadeem R Aburustum - One of the best experts on this subject based on the ideXlab platform.
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the role of systemic chemotherapy in the management of Granulosa Cell tumors
Gynecologic Oncology, 2015Co-Authors: Jane L Meisel, David M Hyman, Anjali R Jotwani, Qin Zhou, Nadeem R Aburustum, Alexia Iasonos, Malcolm C PikeAbstract:Objective Granulosa Cell tumors (GCTs) are rare, and the role of chemotherapy in their management is not clearly defined.
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retroperitoneal nodal metastasis in primary and recurrent Granulosa Cell tumors of the ovary
Gynecologic Oncology, 2006Co-Authors: Nadeem R Aburustum, Antonella Restivo, Joseph J Ivy, Robert A Soslow, Paul Sabbatini, Yukio Sonoda, Richard R Barakat, Dennis S ChiAbstract:Abstract Objective. To describe the incidence of retroperitoneal pelvic or paraaortic lymph node metastasis in patients with primary and recurrent ovarian Granulosa Cell tumors. Methods. At Memorial Sloan-Kettering Cancer Center, we conducted a retrospective chart review of all patients with ovarian Granulosa Cell tumors managed as inpatients from January 1991 to July 2005. The initial date of diagnosis ranged from 1971 to 2005. Results. We identified 68 patients with a median age of 49 years (mean, 47.5 years; range, 19–78 years). Sixty-four (94%) patients had adult type and 4 (6%) had juvenile Granulosa Cell tumors. Fifty-three (78%) patients had their initial surgery at another institution and 55 (81%) were incompletely surgically staged at diagnosis due to the absence of pelvic and/or aortic lymph node dissection. Patients were assigned an International Federation of Gynecology and Obstetrics (FIGO) stage that included IA, 39; IC, 15; IIB, 3; IIC, 3; IIIC, 1. In 7 patients, the original stage was not assigned. Only 16 (24%) patients had a pelvic lymph node sampling and 13 (19%) also had a paraaortic lymph node sampling at primary surgery or at restaging surgery performed shortly following initial diagnosis; however, in these cases, lymph nodes were negative for metastasis. The median number of pelvic lymph nodes removed was 10 (mean, 11.6 nodes; range, 0–36 nodes). The median number of paraaortic lymph nodes removed was 4 (mean, 6 nodes; range, 0–19 nodes). Nine of 15 (60%) of patients managed initially at our institution were surgically staged compared to 4 of 53 (7.5%) who were managed initially elsewhere ( P Thirty-four patients with recurrent Granulosa Cell tumors were managed during the study, 31 (91%) had adult type Granulosa Cell tumor, and 3 had juvenile histology. Thirty-three of 34 patients who recurred were incompletely surgically staged at the initial operation. Original "clinical" FIGO stage for patients who recurred included IA, 15; IC, 8; IIB, 1; IIC, 3; IIIC, 1; and in 6 patients, the original stage was not available. The median disease-free interval to first recurrence was 63 months (mean,69.4 months; range, 4–170 months). First recurrence sites included pelvis, 24/34 (70%); pelvis and abdomen, 3 (9%); retroperitoneum only, 2 (6%); pelvis and retroperitoneum, 2 (6%); pelvis/abdomen/retroperitoneum, 1(3%); abdomen only, 1 (3%); and bone, 1 (3%). Conclusions. Complete surgical staging was performed in approximately 1/5 women with ovarian Granulosa Cell tumors; however, in those initially surgically staged, no nodal metastasis was identified. Clinical stage IA disease was the most common original diagnosis in women who recurred, and approximately 15% of first recurrences appear to involve the retroperitoneum.
Dennis S Chi - One of the best experts on this subject based on the ideXlab platform.
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retroperitoneal nodal metastasis in primary and recurrent Granulosa Cell tumors of the ovary
Gynecologic Oncology, 2006Co-Authors: Nadeem R Aburustum, Antonella Restivo, Joseph J Ivy, Robert A Soslow, Paul Sabbatini, Yukio Sonoda, Richard R Barakat, Dennis S ChiAbstract:Abstract Objective. To describe the incidence of retroperitoneal pelvic or paraaortic lymph node metastasis in patients with primary and recurrent ovarian Granulosa Cell tumors. Methods. At Memorial Sloan-Kettering Cancer Center, we conducted a retrospective chart review of all patients with ovarian Granulosa Cell tumors managed as inpatients from January 1991 to July 2005. The initial date of diagnosis ranged from 1971 to 2005. Results. We identified 68 patients with a median age of 49 years (mean, 47.5 years; range, 19–78 years). Sixty-four (94%) patients had adult type and 4 (6%) had juvenile Granulosa Cell tumors. Fifty-three (78%) patients had their initial surgery at another institution and 55 (81%) were incompletely surgically staged at diagnosis due to the absence of pelvic and/or aortic lymph node dissection. Patients were assigned an International Federation of Gynecology and Obstetrics (FIGO) stage that included IA, 39; IC, 15; IIB, 3; IIC, 3; IIIC, 1. In 7 patients, the original stage was not assigned. Only 16 (24%) patients had a pelvic lymph node sampling and 13 (19%) also had a paraaortic lymph node sampling at primary surgery or at restaging surgery performed shortly following initial diagnosis; however, in these cases, lymph nodes were negative for metastasis. The median number of pelvic lymph nodes removed was 10 (mean, 11.6 nodes; range, 0–36 nodes). The median number of paraaortic lymph nodes removed was 4 (mean, 6 nodes; range, 0–19 nodes). Nine of 15 (60%) of patients managed initially at our institution were surgically staged compared to 4 of 53 (7.5%) who were managed initially elsewhere ( P Thirty-four patients with recurrent Granulosa Cell tumors were managed during the study, 31 (91%) had adult type Granulosa Cell tumor, and 3 had juvenile histology. Thirty-three of 34 patients who recurred were incompletely surgically staged at the initial operation. Original "clinical" FIGO stage for patients who recurred included IA, 15; IC, 8; IIB, 1; IIC, 3; IIIC, 1; and in 6 patients, the original stage was not available. The median disease-free interval to first recurrence was 63 months (mean,69.4 months; range, 4–170 months). First recurrence sites included pelvis, 24/34 (70%); pelvis and abdomen, 3 (9%); retroperitoneum only, 2 (6%); pelvis and retroperitoneum, 2 (6%); pelvis/abdomen/retroperitoneum, 1(3%); abdomen only, 1 (3%); and bone, 1 (3%). Conclusions. Complete surgical staging was performed in approximately 1/5 women with ovarian Granulosa Cell tumors; however, in those initially surgically staged, no nodal metastasis was identified. Clinical stage IA disease was the most common original diagnosis in women who recurred, and approximately 15% of first recurrences appear to involve the retroperitoneum.
Peter J Fuller - One of the best experts on this subject based on the ideXlab platform.
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the foxl2 c134w mutation is characteristic of adult Granulosa Cell tumors of the ovary
Modern Pathology, 2010Co-Authors: Stacey Jamieson, Markku Heikinheimo, Ralf Butzow, Noora Andersson, Maria Alexiadis, Leila Unkilakallio, Peter J Fuller, Mikko AnttonenAbstract:Granulosa Cell tumors of the ovary represent ∼5% 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 wild-type 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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Signalling pathways in the molecular pathogenesis of ovarian Granulosa Cell tumours
Trends in endocrinology and metabolism: TEM, 2004Co-Authors: Peter J Fuller, Simon ChuAbstract:Granulosa Cell tumours represent approximately 5% of all malignant ovarian tumours. They exhibit many morphological, biochemical and hormonal features of proliferating normal preovulatory Granulosa Cells, including both estrogen and inhibin biosynthesis. The aetiology of these tumours remains unclear, although many recent studies and several animal models have focused on signalling pathways that are known to be important in the regulation of Granulosa Cell proliferation. Here, we discuss the information currently available about the possible molecular changes that might lead to neoplastic transformation in human Granulosa Cells. The identification of these changes might lead not only to improved diagnosis, management and treatment of Granulosa Cell tumours, but could also offer new insights into normal Granulosa Cell biology.
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Molecular pathogenesis of Granulosa Cell tumours
Molecular and cellular endocrinology, 2002Co-Authors: Peter J Fuller, Simon Chu, Sonay Fikret, Henry G. BurgerAbstract:Abstract Granulosa Cell tumours (GCT) of the ovary arise from Granulosa Cells of the ovary on morphological, biochemical and molecular criteria. In order to understand the molecular pathogenesis of these tumours better we have sought to define their molecular phenotype, to identify activating mutations of the FSH-signalling pathway, to characterise their estrogen receptor expression and to explore the hypothesis that GCT may be resistant to inhibin. The pattern of gene expression observed in GCT suggests a phenotype which is similar to that of late preovulatory Granulosa Cells which would be consistent with activation of the FSH receptor signalling pathway, however, there is no evidence for activating mutations of either the FSH receptor or the associated trimeric G-proteins. Estrogen receptor β is abundantly expressed in GCT. The various subunits and isoforms of the activin-inhibin receptor are expressed in GCT. These observations provide a basis for future studies of GCT, including further characterisation of signalling pathways known to be important in the regulation of Granulosa Cell growth and differentiation.
Rodolfo A. Rey - One of the best experts on this subject based on the ideXlab platform.
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Ovarian Granulosa Cell Tumors Express a Functional Membrane Receptor for Anti-Müllerian Hormone in Transgenic Mice
Endocrinology, 2001Co-Authors: Martin Dutertre, Jean-yves Picard, Lucile Gouédard, Françoise Xavier, Wen-qing Long, Nathalie Di Clemente, Rodolfo A. ReyAbstract:Anti-Mullerian hormone inhibits Granulosa Cell growth and function. Both anti-Mullerian hormone and its type II receptor are expressed in normal Granulosa Cells. We show by histologic and molecular analyses that ovarian tumors developing in transgenic mice, obtained by targeted oncogenesis using an anti-Mullerian hormone promoter-SV40 oncogene construct, are of Granulosa-Cell origin. Because tissue-specific, Cell-surface molecules are of particular interest for the analysis and treatment of tumors, we examined the expression of anti-Mullerian hormone type II receptor in the ovaries of these transgenic mice. We demonstrate that the anti-Mullerian hormone type II receptor is expressed not only in normal ovarian follicles, but also in Granulosa Cell tumors. Using a Cell line derived from one of these tumors, we show that the anti-Mullerian hormone type II receptor protein is present on the surface of tumor Cells and binds anti-Mullerian hormone. Furthermore, we show that the anti-Mullerian hormone receptor i...
Thirunavukkarasu Arun Babu - One of the best experts on this subject based on the ideXlab platform.
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Late Recurrence of Granulosa Cell Tumour Involving the Retroperitoneum and Spleen
Indian Journal of Gynecologic Oncology, 2020Co-Authors: Padmapriya Balakrishnan, Vijayan Sharmila, Thirunavukkarasu Arun BabuAbstract:Granulosa Cell tumour of the ovary is a sex-cord stromal tumour that accounts for 2–5% of all ovarian neoplasms. It is a low-grade malignant tumour that is often diagnosed in early stages and has a favourable prognosis. The peculiarity of this tumour is its tendency for late recurrence, and the mean time to recurrence is 5–10 years after initial diagnosis. The risk of late recurrence necessitates long-term follow-up of treated patients. We report an unusual case of late recurrence of Granulosa Cell tumour involving the retroperitoneum and spleen after 20 years of initial treatment.
