Overexpression of p53 Is Not a Feature of Ovarian Granulosa Cell Tumors

Liu, Fu-Shing; Ho, Esther Shih-Chu; Lai, Chiung‐Ru; Chen, Jung‐Ta; Shih, Rocky Tai-Ping; Yang, Chiou-Ying; Tsao, Chien-Ming

doi:10.1006/gyno.1996.0095

Cited by 27 publications

(18 citation statements)

References 3 publications

(5 reference statements)

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“…Bien que le gène WT1 soit exprimé dans les tumeurs de la granulosa, aucune mutation ni perte d'hétérozygotie n'a été identifiée [55]. Les anomalies de p53 sont fréquentes dans plusieurs tumeurs solides, y compris dans les tumeurs épithéliales de l'ovaire, mais ni une hyperexpression de ce gène [56] ni une mutation de ce gène [57] n'est présente dans les tumeurs de la granulosa.…”

Section: Oncogènes Et Voie De La Map-kinaseunclassified

Tumeurs juvéniles de la granulosa : expression clinique et moléculaire

Kalfa¹,

Philibert²,

Patte³

et al. 2009

Gynécologie Obstétrique & Fertilité

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Section: Oncogènes Et Voie De La Map-kinaseunclassified

Tumeurs juvéniles de la granulosa : expression clinique et moléculaire

Kalfa¹,

Philibert²,

Patte³

et al. 2009

Gynécologie Obstétrique & Fertilité

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“…Similarly, very few instances of inactivation of tumor suppressor genes in GCT have been reported thus far. The tumor suppressor genes TP53 and WT1, which are commonly mutated in a broad range of neoplasia, are thought not to play a role in the pathogenesis of GCT (12)(13)(14). One recent report found a lack of expression of the cyclin-dependent kinase inhibitors INK4A and/or INK4B in a significant proportion of GCT (15), suggesting a means by which GCT cells may escape cell cycle control.…”

Section: Introductionmentioning

confidence: 99%

Misregulated Wnt/β-Catenin Signaling Leads to Ovarian Granulosa Cell Tumor Development

et al. 2005

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Misregulation of the Wnt/B-catenin signaling pathway is a hallmark of several forms of cancer. Components of the Wnt/ B-catenin pathway are expressed in ovarian granulosa cells; nevertheless, its potential involvement in granulosa cell tumorigenesis has not been examined. To this end, human (n = 6) and equine (n = 18) granulosa cell tumors (GCT) were analyzed for B-catenin expression by immunohistochemistry. Unlike granulosa cells of normal ovaries, most (15 of 24) GCT samples showed nuclear localization of B-catenin, suggesting that activation of the Wnt/B-catenin pathway plays a role in the etiology of GCT. To confirm this hypothesis, Catnb flox(ex3)/+ ; Amhr2 cre/+ mice that express a dominant stable B-catenin mutant in their granulosa cells were generated. These mice developed follicle-like structures containing disorganized, pleiomorphic granulosa by 6 weeks of age. Even in older mice, these follicle-like lesions grew no larger than the size of antral follicles and contained very few proliferating cells. Similar to corpora lutea, the lesions were highly vascularized, although they did not express the luteinization marker Cyp11a1. Catnb flox(ex3)/+ ; Amhr2 cre/+ females were also found to be severely subfertile, and fewer corpora lutea were found to form in response to exogenous gonadotropin compared with control mice. In older mice, the ovarian lesions often evolved into GCT, indicating that they represent a pretumoral intermediate stage. The GCT in Catnb flox(ex3)/+ ; Amhr2 cre/+ mice featured many histopathologic similarities to the human disease, and prevalence of tumor development attained 57% at 7.5 months of age. Together, these studies show a causal link between misregulated Wnt/B-catenin signaling and GCT development and provide a novel model system for the study of GCT biology. (Cancer Res 2005; 65(20): 9206-15)

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“…Only one case (5%) stained positively for mutant p53. The rates of mutant p53 overexpression in GCTO vary broadly in different reports (5% to 72%) (8)(9)(10)(11)(12)(13)(14) . Besides the problem of limited sample size, this variation occurs due to the limitations of immuno-histochemistry in detecting nuclear accumulation of mutated p53 protein.…”

Section: Discussionmentioning

confidence: 99%

“…The clinical behavior, however, is difficult to predict in individual cases at the time of presentation, and neither histologic nor clinical criteria are useful predictors in terms of the outcome of the disease (2)(3)(4) . During the past decades, a large number of functional biologic markers that might play a causative role in the progression of human tumors have been studied, including tumor suppressor genes or oncogene products, as well as markers of cell proliferation and angiogenic activity (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) .…”

mentioning

confidence: 99%

“…Overexpression of mutant p53 has been reported in up to 79% of epithelial ovarian cancers when assessed by single strand conformation polymorphism analysis and DNA sequencing (7) . In GCTO, p53 overexpression has been reported in 5% to 72% of the cases, but the prognostic value remains unclear due to the conflicting results of several studies (8)(9)(10)(11)(12)(13)(14) .…”

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confidence: 99%

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Expression of p53, c-erbB-2, Ki-67, and CD34 in granulosa cell tumor of the ovary

Kusamura

Derchain

Alvarenga

et al. 2003

International Journal of Gynecological Cancer

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The purpose of this study is to investigate the expression of p53, c-erbB-2, Ki-67, and angiogenic activity and their correlation with the clinicopathologic characteristics in a series of granulosa cell tumors of the ovary (GCTO). Eighteen GCTO cases assisted at the Department of Obstetrics and Gynecology, School of Medical Science, UNICAMP, after diagnostic confirmation by three pathologists, were submitted to immunohistochemistry for assessment of p53, c-erbB-2, Ki-67, and CD34 expressions. The mean tumor size was 13 cm (range: 4–30 cm). Six (33%) cases presented with extraovarian disease. Thirteen (72%) cases presented some solid diffuse or sarcomatoid pattern and six (33%) moderate or strong atypia. Fourteen cases presented ≤2 mitoses/10 HPF. Thirteen cases were focally positive for Ki-67. The mean Ki-67 proliferative index was 1.0%. One case presented positive expression for mutant p53 but all cases were negative for c-erbB-2 expression. The mean microvascular density was 28.9/mm2 (range: 0–50). No significant correlations could be established between the biologic markers and clinicopathologic variables. GCTO showed a markedly low rate of immunohistochemical staining for p53 or c-erbB-2 overexpression/amplification, as well as low proliferative and angiogenic activities. Further studies are urgently needed to elaborate the factors responsible for the highly unpredictable clinical course of GCTO.

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Overexpression of p53 Is Not a Feature of Ovarian Granulosa Cell Tumors

Cited by 27 publications

References 3 publications

Tumeurs juvéniles de la granulosa : expression clinique et moléculaire

Tumeurs juvéniles de la granulosa : expression clinique et moléculaire

Misregulated Wnt/β-Catenin Signaling Leads to Ovarian Granulosa Cell Tumor Development

Expression of p53, c-erbB-2, Ki-67, and CD34 in granulosa cell tumor of the ovary

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