PTEN immunohistochemical expression is suppressed in G1 endometrioid adenocarcinoma of the uterine corpus

Kimura, Futoshi; Watanabe, Jun; Hata, Hiroki; Fujisawa, T; Kamata, Yuko; Nishimura, Yukari; Jobo, Toshiko; Kuramoto, Hiroyuki

doi:10.1007/s00432-003-0517-8

Cited by 40 publications

(34 citation statements)

References 29 publications

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“…A finding that agrees with Kapucuoglu et al (2007); Abd El-Maqsoud and ElGelany (2009); Sarmadi et al (2009);and Lee et al (2012), whose studies reported a significantly lower PTEN scores in atypical hyperplasia compared with endometrial hyperplasia, and incompatible with Kimura et al (2004) and Xiong et al (2010), who showed no significant differences among subtypes of hyperplasia. (72) EECA versus PE and EH (P < 0.001) for both; AH versus PE and EH (P = 0.0015, P < 0.001); EECA versus AH (P = 0.2) nonsignificant, respectively.…”

Section: Discussionsupporting

confidence: 67%

Expression and significance of PTEN and GLUT-1 in proliferative endometrium, endometrial hyperplasia, and endometrioid adenocarcinoma

Raouf¹,

Hamid²

2014

Egyptian Journal of Pathology

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Background Endometrioid endometrial carcinoma accounts for more than three-fourths of endometrial cancers and is thought to develop following a continuum of premalignant lesions. It is important to identify the subset of hyperplasia that is associated strongly with malignancy. Recent molecular diagnostic methods have provided new ancillary tools for premalignant lesion diagnosis.Aim The aim of the study is to determine the variability in phosphotensin tumor-suppressor gene (PTEN) and glucose transporter protein-1 (GLUT-1) expression patterns in proliferative endometrium, endometrial hyperplasia, and endometrioid adenocarcinoma.Materials and methods A total of 60 archived formalinfixed and paraffin-embedded specimens were obtained for this study. Specimens included 10 cases with proliferative endometrium; 17 cases with endometrial hyperplasia without atypia (15 cases were simple and two cases were complex); eight cases with atypical endometrial hyperplasia; and 25 cases with endometrioid adenocarcinoma specimens (16 cases were grade I, six cases were grade II, and three cases were grade III). Endometrial samples were obtained either by curettage or biopsy specimens, and sections were immunostained for PTEN and GLUT-1 protein expression.Results Complete loss of PTEN immunoreactivity was found in none of the 10 cases with proliferative endometrium; one of the 17 (5.9%) cases with endometrial hyperplasia without atypia; five of the eight (62.5%) cases with atypical hyperplasia; and 16 of the 25 (64%) cases with endometrioid adenocarcinoma. Overexpression of GLUT-1 protein was present in six of the eight (75%) cases with atypical hyperplasia and 23 of the 25 (92%) cases with endometrioid adenocarcinoma. With regard to the grades of endometrioid adenocarcinoma, a progressive reduction in the number of PTEN-positive glands and increase in GLUT-1 expression was observed with higher grades.Conclusion Lack of PTEN expression and overexpression of GLUT-1 may be early events in the tumorigenesis of endometrioid adenocarcinoma. The combination of PTEN-negative/GLUT-1-positive results may be useful in distinguishing benign hyperplasia from endometrial intraepithelial neoplasia and endometrioid adenocarcinoma.

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Section: Discussionsupporting

confidence: 67%

Expression and significance of PTEN and GLUT-1 in proliferative endometrium, endometrial hyperplasia, and endometrioid adenocarcinoma

Raouf¹,

Hamid²

2014

Egyptian Journal of Pathology

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“…In summary, our data strongly suggest that supraphysiologic activation of ERa is, in vivo, an obligatory pathway for the development of endometrial lesions consequent to loss of Pten and activation of Akt. The functional connection between these molecules is further underlined by the fact that loss of PTEN is typically found in EECs expressing high levels of ERa (21). Similarly, the same axis is likely to play a pivotal role in the development of ERa-positive breast cancer.…”

Section: Resultsmentioning

confidence: 99%

Akt-Mediated Phosphorylation and Activation of Estrogen Receptor α Is Required for Endometrial Neoplastic Transformation in Pten+/− Mice

Vilgelm¹,

Zhou²,

Wang

et al. 2006

Cancer Research

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PTEN is a tumor suppressor gene frequently mutated in human cancers. In vitro and in vivo studies have shown that PTEN can exert its tumor suppressive function through a variety of mechanisms, including regulation of cell death and cell proliferation. However, it is still unclear which of the many downstream pathways are critical in each different tissue, in vivo. Loss of PTEN is the earliest detectable genetic lesion in the estrogen-related type I (endometrioid) endometrial cancer. Pten +/À mice develop endometrial neoplastic lesions with full penetrance, thus providing a model system to dissect the genetic and biochemical events leading to the transition from normal to hyperplastic and neoplastic endometrial epithelium. Here, we show that loss of Pten in the mouse endometrium activates Akt and results in increased phosphorylation of estrogen receptor A (ERA) on Ser 167 . ERA phosphorylation results, in turn, in the activation of this nuclear receptor both in vivo and in vitro, even in the absence of ligand, and in its increased ability to activate the transcription of several of its target genes. Strikingly, reduction of endometrial ERA levels and activity dramatically reduces the neoplastic effect of Pten loss in the endometrium, in contrast to complete estrogen depletion. Thus, we provide for the first time in vivo evidence supporting the hypothesis that loss of Pten and subsequent Akt activation result in the activation of ERA-dependent pathways that play a pivotal role in the neoplastic process. (Cancer Res 2006; 66(7): 3375-80)

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“…AMPK activation by metformin is not only necessary for inhibition of gluconeogenesis in hepatocytes and reduction of Acetyl-CoA carboxylase (ACC) activity and hence fatty acid oxidation [75], but also for its growth-inhibitory effect in epithelial cells [76] an effect associated with decreased mTOR and S6 kinase activation. Several studies have now demonstrated that activation of AMPK suppresses mTOR signaling induced by growth factors and amino acids [40,[78][79][80][81] directly or indirectly (via TSC2). Signaling through mTOR up-regulates many energy-consuming cellular processes: mTOR has a central role in regulating cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism (reviewed in Refs.…”

Section: Targeting Ampk By Metforminmentioning

confidence: 99%

Targeting AMPK: A new therapeutic opportunity in breast cancer

Hadad

Fleming

Thompson

2008

Critical Reviews in Oncology/Hematology

145

127

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PTEN immunohistochemical expression is suppressed in G1 endometrioid adenocarcinoma of the uterine corpus

Cited by 40 publications

References 29 publications

Expression and significance of PTEN and GLUT-1 in proliferative endometrium, endometrial hyperplasia, and endometrioid adenocarcinoma

Expression and significance of PTEN and GLUT-1 in proliferative endometrium, endometrial hyperplasia, and endometrioid adenocarcinoma

Akt-Mediated Phosphorylation and Activation of Estrogen Receptor α Is Required for Endometrial Neoplastic Transformation in Pten+/− Mice

Targeting AMPK: A new therapeutic opportunity in breast cancer

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