PTEN expression in clear cell adenocarcinoma of the ovary

Hashiguchi, Yasunori; Tsuda, Hiroshi; Inoue, Takeshi; Berkowitz, Ross S.; Mok, Samuel C.

doi:10.1016/j.ygyno.2005.09.047

Cited by 76 publications

(47 citation statements)

References 18 publications

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“…In the current study PTEN staining was of prognostic significance mainly in the stage I/II group and in poorly differentiated serous carcinomas. We found negative PTEN expression in 30.8% of tumours, which is in agreement with previous studies Lee et al, 2005a;Hashiguchi et al, 2006). In ovarian cancer, loss-ofheterozygosity (LOH) at the PTEN locus (10q23.3) occurs in 31 -45% of tumours, whereas mutations of the second PTEN allele are relatively rare Obata et al, 1998;Kurose et al, 2001).…”

Section: Discussionsupporting

confidence: 92%

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The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer

et al. 2008

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Ovarian cancer is the most frequent cause of death from gynaecological cancer in the Western world. Current prognostic factors do not allow reliable prediction of response to chemotherapy and survival for individual ovarian cancer patients. Epidermal growth factor receptor (EGFR) and HER-2/neu are frequently expressed in ovarian cancer but their prognostic value remains unclear. In this study, we investigated the expression and prognostic value of EGFR, EGFR variant III (EGFRvIII), HER-2/neu and important downstream signalling components in a large series of epithelial ovarian cancer patients. Immunohistochemical staining of EGFR, pEGFR, EGFRvIII, Her-2/neu, PTEN (phosphatase and tensin homologue deleted on chromosome 10), total and phosphorylated AKT (pAKT) and phosphorylated ERK (pERK) was performed in 232 primary tumours using the tissue microarray platform and related to clinicopathological characteristics and survival. In addition, EGFRvIII expression was determined in 45 tumours by RT -PCR. Our results show that negative PTEN immunostaining was associated with stage I/II disease (P ¼ 0.006), non-serous tumour type (P ¼ 0.042) and in multivariate analysis with a longer progression-free survival (P ¼ 0.015). Negative PTEN staining also predicted improved progression-free survival in patients with grade III or undifferentiated serous carcinomas (P ¼ 0.011). Positive pAKT staining was associated with advanced-stage disease (P ¼ 0.006). Other proteins were expressed only at low levels, and were not associated with any clinicopathological parameter or survival. None of the tumours were positive for EGFRvIII. In conclusion, our results indicate that tumours showing negative PTEN staining could represent a subgroup of ovarian carcinomas with a relatively favourable prognosis.

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Section: Discussionsupporting

confidence: 92%

“…A high rate of PTEN loss in clear cell and endometrioid carcinomas has also been shown in previous, much smaller studies (Obata et al, 1998;Hashiguchi et al, 2006). Both cancers are thought to at least partly arise from endometriosis.…”

Section: Discussionsupporting

confidence: 64%

The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer

et al. 2008

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“…Loss of PTEN protein expression is also found in one-third of the ovarian clear cell carcinoma patients. 22 To our knowledge, no study has reported the combination of all these common molecular genetic alterations in the same patient cohort.…”

Section: Discussionmentioning

confidence: 97%

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

et al. 2014

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AT-rich interactive domain 1A (ARID1A) is a subunit of switch/sucrose non-fermentable (SWI/SNF) complex. Recently, alterations of ARID1A gene, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway and zinc-finger protein 217 (ZNF217) gene have been identified as frequent molecular genetic changes in ovarian clear cell carcinoma. The relationships between these events have not been studied and integrated in the same cohort. This study was aimed at determining the correlation between these molecular events and other clinicopathological factors, including the prognostic impacts of these clinicopathological factors. A total of 68 ovarian clear cell carcinoma cases were collected and subjected to immunohistochemistry testing for ARID1A, SMARCA2, SMARCA4, SMARCB1 and phosphatase and tensin homolog (PTEN), mutation analysis for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene and fluorescence in situ hybridization for ZNF217 amplification. The correlations between ARID1A expression, PI3K-Akt pathway, ZNF217 amplification and other clinicopathological factors were analyzed. Loss of ARID1A expression was present in 35 cases (52%) and loss of SMARCA2 expression occurred in 1 case. SMARCA4 and SMARCB1 expressions were preserved in all cases. PIK3CA mutations were present in 23 cases (34%) and loss of PTEN expression occurred in 8 cases (12%). Alterations in the PI3K-Akt pathway (PIK3CA mutations or loss of PTEN expression) were found in 42 cases (62%). ZNF217 amplification was detected in 21 cases (31%). Loss of ARID1A expression was significantly related to younger patient age (P ¼ 0.048), PI3K-Akt pathway activation (P ¼ 0.046) and ZNF217 amplification (P ¼ 0.028). All of the clinicopathological factors were not prognostic factors for ovarian clear cell carcinoma after multivariate analysis, except International Federation of Gynecology and Obstetrics staging (P ¼ 0.001). Our results showed that loss of ARID1A expression usually coexisted with PI3K-Akt pathway activation and/or ZNF217 amplification. Synergic effects of loss of ARID1A and PI3K-Akt pathway activation as well as ZNF217 amplification may be related to the development of ovarian clear cell carcinoma.

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“…Activation of Akt is observed in up to 70% of ovarian cancers (4) due to a variety of causes, including PIK3CA mutations (8%-12%) or amplification (3%-8%) and/or PTEN loss (27%) or mutations (3-8%) (1,(5)(6)(7)(8)(9)(10). Loss of Pten (11,12) or overexpression of activated PI3K in the mouse ovarian surface epithelium (OSE) (13) do not lead to tumor formation; however, the ability of mutant Pik3ca to initiate tumorigenesis or drive tumor progression has not been established.…”

Section: Introductionmentioning

confidence: 99%

An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice

et al. 2012

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PTEN expression in clear cell adenocarcinoma of the ovary

Cited by 76 publications

References 18 publications

The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer

The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice

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