Granulosa Cell Tumor of Ovary: A Clinicopathologic and Flow Cytometric DNA Analysis

Roush, Gregory R.; El‐Naggar, Adel K.; Abdul‐Karim, Fadi W.

doi:10.1006/gyno.1995.1076

Cited by 26 publications

(10 citation statements)

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“…Several groups of investigators have reported that diploidy is associated with favorable prognosis (31)(32)(33)(34)(35); however, in the present study ploidy and survival were not correlated. It has been pointed out (27,36) that image cytometric analysis is not sensitive enough to detect small changes in nuclear DNA content.…”

Section: Discussioncontrasting

confidence: 91%

Characteristic Pattern of Genetic Aberrations in Ovarian Granulosa Cell Tumors

Mayr¹,

Kaltz-Wittmer²,

Arbogast³

et al. 2002

Mod Pathol

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The cytogenetic abnormalities of granulosa cell tumors (GCT) of the ovary are only partially known. Up to now, mainly numerical chromosomal aberrations have been described. Therefore we performed a comprehensive study on paraffin-embedded material of 20 GCT (17 adult, 3 juvenile; patient age between 16 and 78 y) combining comparative genomic hybridization (CGH); fluorescence in situ hybridization (FISH) using DNA-specific probes for chromosome 12, 17, 22, and X; DNA cytometry; and immunohistochemistry (inhibin, p53, Ki67).By DNA cytometry, 16 of 20 tumors (80%) were diploid. However, 6 of 16 diploid tumors (37%) showed aberrations by FISH. FISH revealed monosomy 22 in 8/18 cases (40%); trisomy 12 in 5/20 (25%); monosomy X in 2/20 (10%); and loss of chromosome 17 in one case (5%). The main findings by CGH were gains of chromosomes 12 (6 cases, 33%) and 14 (6 cases, 33%) and losses of chromosomes 22 (7 cases, 35%) and X (1 case, 5%), mostly comprising whole chromosomes or chromosome arms. Inhibin and p53 were expressed in 100% and 95% of the tumors, respectively. The Ki67 index ranged from 0% to 61%. Neither immunohistochemistry, nor DNA cytometry and molecular genetic analysis, provided statistically significant prognostic information.In summary, our study reveals a distinctive pattern of cytogenetic alterations in GCT. Our observations confirm earlier reports that trisomy 12 and 14 are frequent aberrations; however, monosomy 22 seemingly is even more prevalent. Granulosa cell tumors of the ovary (GCT) are much less common than epithelial ovarian cancer. These tumors account for 1.5% of all ovarian neoplasms and for 6% of malignant ovarian tumors. Sixty-five percent of patients are postmenopausal; Ͻ5% are prepubertal. The juvenile granulosa cell tumor is a distinctive form of GCT that occurs almost exclusively in children and young adults. More than 95% of the GCT are unilateral and confined to the ovary.

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Section: Discussioncontrasting

confidence: 91%

Characteristic Pattern of Genetic Aberrations in Ovarian Granulosa Cell Tumors

Mayr¹,

Kaltz-Wittmer²,

Arbogast³

et al. 2002

Mod Pathol

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“…According to some investigators aneuploidy was not a predictor for recurrence, 58,[62][63][64] whereas others found that aneuploidy was associated with high risk for recurrence. [65][66][67][68] Similar conflicting results have been reported for p53 overexpression; some investigators demonstrated that this was an adverse prognostic factor, 62,69,70 whereas others showed no association with outcome. 54,57,61,71 Staining of granulosa cell tumors for Ki-67 showed that a high Ki-67 index was correlated with an adverse prognosis in some studies [60][61][62] but not in others.…”

Section: Prognostic Factorsmentioning

confidence: 60%

Granulosa Cell Tumor of the Ovary: Tumor Review

et al. 2008

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Granulosa cell tumors of the ovary are rare neoplasms that originate from sex-cord stromal cells. The long natural history of granulosa cell tumors and their tendency to recur years after the initial diagnosis are the most prominent of their characteristics. The secretion of estradiol is the reason for signs at presentation such as vaginal bleeding and precocious puberty. Abdominal pain and hemoperitoneum, which occasionally can occur, are attributable to tumor rupture. The most common finding in pelvic examination is a tumor mass, which is subsequently confirmed with imaging techniques. Surgery is the mainstay of initial management for histological diagnosis, appropriate staging, and debulking. A more conservative unilateral salpingo-oophorectomy is indicated in patients with stage I disease and patients of reproductive age. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the appropriate surgical treatment for postmenopausal women and those with more advanced disease. The stage of disease is the most important prognostic factor associated with the risk of relapse. There are no clear conclusions regarding the role of postoperative chemotherapy or radiotherapy in stage I disease and in those with completely resected tumor. The use of adjuvant chemotherapy or radiotherapy has sometimes been associated with prolonged disease-free survival and possibly overall survival. Chemotherapy is the treatment of choice for patients with advanced, recurrent, or metastatic disease, and BEP (bleomycin, etoposide, and cisplatin) is the preferred regimen. Although the overall rate of response to treatment is high, the impact of treatment on disease-free or overall survival is unknown. Prolonged surveillance is mandatory because tumors tend to recur years after the initial diagnosis.

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“…The results are conflicting, with some authors finding no prognostic significance,17 27 30 36 while others have reported a significantly higher rate of recurrence in aneuploid tumours 25 29 32 37. One study showed a significant correlation between aneuploidy and other potential prognostic variables such as high tumour stage, but a non-significant tendency toward recurrence 38. Some authors have found S-phase fraction values ranging from >6% to >10% to be associated with an increased likelihood of recurrence 25 29 32.…”

Section: Dna Aneuploidymentioning

confidence: 99%