Loss of PTEN expression is an independent predictor of favourable survival in endometrial carcinomas

Akiyama-Abe, Azusa; Minaguchi, Takeo; Nakamura, Yuko; Michikami, Hiroo; Shikama, Ayumi; Nakao, Sari; Sakurai, Minoru; Ochi, Hiroki; Onuki, Mamiko; Matsumoto, Koji; Oki, Akinori; Yoshikawa, Hiroyuki

doi:10.1038/bjc.2013.455

Cited by 40 publications

(35 citation statements)

References 12 publications

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“…With regards to PTEN status in EEC, several studies report that there is an association with PTEN status and progression in EEC but even here there are discrepancies. Some studies state that a PTEN-positive status is associated with a favourable prognosis (Kanamori et al 2002, Uegaki et al 2005 and that with higher stages of EEC, PTEN loss increases (Daniilidou et al 2013), but two studies suggest that a PTEN-negative status is associated with a favourable prognosis (Mackay et al 2010, Akiyama-Abe et al 2013. The present study found no association between PTEN status and progression-free survival in EEC or any difference between PTEN status and FIGO stage.…”

Section: Discussioncontrasting

confidence: 54%

Assessing the prognostic value of PAX2 and PTEN in endometrial carcinogenesis

Rewcastle¹,

Varhaugvik²,

Gudlaugsson³

et al. 2018

Endocrine-Related Cancer

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E Rewcastle et al.PAX2 in endometrial neoplasia 981-991 AbstractIn order to avoid the consequences of over-and under-treatment of endometrial hyperplasia, diagnostic accuracy and progression risk assessment must be improved. The aim of this study was to assess whether PAX2 or PTEN expression could predict progression-free survival in endometrial intraepithelial neoplasia (EIN) and endometrial endometrioid carcinoma (EEC). Immunohistochemistry for detection of PAX2 and PTEN was performed on 348 endometrial samples; 75 proliferative endometrium (PE), 36 EIN and 237 EEC. Cases classified as PTEN null (1 or more glands negatively stained) were more prevalent in EEC than in PE and EIN (64% EEC vs 11% PE/EIN). A progressive decrease in PAX2 expression was observed from PE to EIN to EEC. Long-term clinical follow-up (6-310 months, median: 126) was available for 62 PE cases, all 36 EIN cases and 178 EEC cases. No patients with PE demonstrated progression to EIN or EEC.Progression of disease was observed in 10 (28%) EIN patients. These patients had significantly lower PAX2 expression than those that regressed (P = 0.005). Progression-free survival analysis revealed that EIN patients with a high-risk PAX2 expression score (H-score ≤75) had a higher probability of progression of disease in comparison to those with a low-risk score (H-score >75). PAX2 expression was not prognostic in EEC nor was PTEN status of prognostic value in either EIN or EEC. PAX2 expression analysis by means of H-score has prognostic potential for the identification of high-risk progression cases in EIN but needs to be validated in a larger cohort.Endocrine-Related Cancer (2018) 25, 981-991

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Section: Discussioncontrasting

confidence: 54%

Assessing the prognostic value of PAX2 and PTEN in endometrial carcinogenesis

Rewcastle¹,

Varhaugvik²,

Gudlaugsson³

et al. 2018

Endocrine-Related Cancer

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“…Mutations in the PTEN gene, a tumor suppressor and a negative regulator of PI3K activation, are thought to be one of the earliest events in Type I EC tumorigenesis, while PIK3CA mutations occur late and are thought to be associated with invasion . PTEN immunohistochemistry has the ability to capture functional PTEN loss in addition to genomic PTEN loss, and has been shown to be an independent predictor of favorable survival in endometrial cancer . Mutations in AKT, the primary effector of PI3K activity, are thus far rarely reported in endometrial cancer .…”

Section: Resultsmentioning

confidence: 99%

“…20 PTEN immunohistochemistry has the ability to capture functional PTEN loss in addition to genomic PTEN loss, 21 and has been shown to be an independent predictor of favorable survival in endometrial cancer. 22,23 Mutations in AKT, the primary effector of PI3K activity, are thus far rarely reported in endometrial cancer. 24 Figure 2b shows that the PI3K/ PTEN/AKT pathway is most frequently dysregulated within Type I and mucinous histology, with PIK3CA mutated in 36% of Type I and 33% mucinous; PTEN mutated in 41% Type I and 50% mucinous; PTEN loss in 70% of Type I and mucinous EC; and AKT mutation in 5% of EC and 6% of mucinous samples.…”

Section: Genomic and Molecular Characterizationmentioning

confidence: 99%

Distinct molecular landscapes between endometrioid and nonendometrioid uterine carcinomas

et al. 2017

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Endometrial carcinoma (EC) is traditionally characterized as endometrioid and nonendometrioid based on histopathologic phenotypes. Molecular-based classifications have been proposed, but are not widely implemented. Herein we examine molecular profiles between EC histologic subtypes. 3133 ECs were submitted between March 2011 and July 2014: 1634 Type I and 1226 Type II. In situ hybridization and immunohistochemistry were used to assess copy number and protein expression of selected genes. Sequenced variants in 47 genes were analyzed using the Illumina TruSeq Amplicon Cancer Panel. Type II EC included 628 cases of uterine serous cancer (USC), 136 cases of clear cell (CC), 361 cases of carcinosarcoma (CS), 38 cases of mucinous, and 36 cases of squamous cell. PI3K/Akt/mTOR pathway was most frequently dysregulated within Type I and mucinous histologies, least altered in CS and squamous. PD-L1 expression was highest in mucinous, absent in squamous. ER/PR expression was common in Type II, most frequent in USC, mucinous, and squamous. Receptor tyrosine kinase was frequently dysregulated in Type II disease: HER2 amplification highest in USC and CC, EGFR mutations exclusively seen in mucinous EC, KRAS mutations common in mucinous, squamous, and Type I, and c-MET overexpression high in CC and mucinous. BRCA1 and BRCA2 were most frequently mutated in CS. Grade 3 EC shares features of G1 tumor and Type II disease, most notably resembling CS. Endometrial carcinomas are a molecularly heterogeneous group of tumors. A histology-based molecular map can identify rational targets to optimize treatment and guide future clinical trials.

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“…PTEN gene mutations are seen in 18-55% of endometrial precancers, 26-80% of endometrioid adenocarcinomas [16]. Akiyama-Abe et al reported that expression of PTEN was lost in 56 endometrial carcinoma patients (25%) [17]. Heejeong et al showed that PTEN loss was significantly higher in endometrial carcinoma compared with simple hyperplasia (68% vs. 24%), and it was also higher in complex atypical hyperplasia compared with simple hyperplasia (71% vs. 24%) [18].…”

Section: Discussionmentioning

confidence: 99%

PTEN, PAX2 and PINCH protein expression in normal endometrium, endometrial hyperplasia, and endometrioid adenocarcinomas

Karakuş¹

2018

Ann Clin Anal Med

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Aim: The purpose of this study was to investigate the role of PTEN, PAX2 and PINCH protein expressions in endometrial carcinogenesis. Material and Method: In this study 27 proliferative endometrium, 24 complex atypical hyperplasia, 10 complex hyperplasia without atypia, 30 simple hyperplasia without atypia, and 89 endometrioid type endometrial adenocarcinoma cases were enrolled. PTEN, PAX2 and PINCH antibodies were applied immunohistochemically to these cases. Results: Results of immunohistochemical staining revealed that during progression from normal to malignancy, staining distribution and intensity of both PTEN and PAX2 were found to decrease significantly. Expression of PINCH, on the other hand, was found to be increased distinctly during progression from normal to malignancy which correlated reversely with PAX2 and PTEN expressions. When PTEN, PAX2 and PINCH expressions in endometrioid adenocarcinoma cases were compared with common histopathologic prognostic parameters, a relation between histopathologic grade, angiolymphatic invasion, lymph node metastasis, stage, myometrial invasion and involvement of corpus cervix margin was not detected. Discussion: In conclusion, we suggest that the absence of PTEN and PAX2 expression seem to be associated with the progression of endometrioid carcinomas. Expression of PINCH, on the other hand, was found to be increased distinctly during progression from normal to malignancy. Further studies are necessary to define the biological role of PTEN, PAX2, and PINCH. PTEN, PAX2, and PINCH may have prognostic importance and predictive value for targeted therapies. Those expression profiles of biomarkers might also be expected to identify those patients with endometrial hyperplasia who are at risk of developing carcinoma.

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Loss of PTEN expression is an independent predictor of favourable survival in endometrial carcinomas

Cited by 40 publications

References 12 publications

Assessing the prognostic value of PAX2 and PTEN in endometrial carcinogenesis

Assessing the prognostic value of PAX2 and PTEN in endometrial carcinogenesis

Distinct molecular landscapes between endometrioid and nonendometrioid uterine carcinomas

PTEN, PAX2 and PINCH protein expression in normal endometrium, endometrial hyperplasia, and endometrioid adenocarcinomas

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