Expression pattern of PAX2 in hyperplastic and malignant endometrium

Kahraman, Korhan; Kiremitci, Saba; Taşkın, Salih; Kankaya, Duygu; Sertçelik, Ayşe; Ortaç, Fırat

doi:10.1007/s00404-012-2236-3

Cited by 15 publications

(21 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kahraman et al showed that the mean percentages of PAX2 staining cells were 80.8, 96.7, 88.6, 92.7, and 99.2 with proliferative endometrium, atrophic endometrium, complex hyperplasia, complex atypical hyperplasia, and adenocarcinoma, respectively. Similar to our study, they did not find any correlation between PAX2 expression levels and the stage, histological grade, myometrial invasion, and lymph node status in cancer cases [20]. We investigated the correlation of expression of PTEN and PAX2.…”

Section: Discussionsupporting

confidence: 63%

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

Karakuş¹

2018

Ann Clin Anal Med

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 63%

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

Karakuş¹

2018

Ann Clin Anal Med

View full text Add to dashboard Cite

show abstract

“…Regarding the assessment of risk of bias among the studies, for the "patient selection" domain, four studies were categorized as being at low risk of bias, because they included consecutive patients, whereas one was classified at unclear risk because it did not report this information, 15 and one was high risk because it only selected cases previously diagnosed as non-atypical hyperplasia. 14 Concerns about the applicability of this domain were considered high for one study, because it assessed only EH of women treated with progestin.…”

Section: Re Sultsmentioning

confidence: 99%

“…14 Concerns about the applicability of this domain were considered high for one study, because it assessed only EH of women treated with progestin. 15,19 For the "reference standard" domain, five studies were categorized at low risk of bias since they reported a blinded re-evaluation of specimens, whereas one was classified at unclear risk because this information was not clearly reported. 15,19 For the "reference standard" domain, five studies were categorized at low risk of bias since they reported a blinded re-evaluation of specimens, whereas one was classified at unclear risk because this information was not clearly reported.…”

Section: Re Sultsmentioning

confidence: 99%

PAX2 in endometrial carcinogenesis and in differential diagnosis of endometrial hyperplasia: A systematic review and meta‐analysis of diagnostic accuracy

Raffone

Travaglino

Saccone

et al. 2019

Acta Obstet Gynecol Scand

View full text Add to dashboard Cite

Abbreviations: AUC, area under the curve; DOR, diagnostic odds ratio; EC, endometrial cancer; EH, endometrial hyperplasia; EIN, endometrial intraepithelial neoplasia; ESGO, European Society of Gynaecological Oncology; LR+, positive likelihood ratio; LR−, negative likelihood ratio; NE, normal endometrium; PAX2, paired box 2 protein; SROC, summary receiver operating characteristic; WHO, World Health Organization. Abstract Introduction: Benign and precancerous endometrial hyperplasias (EH) are differentiated according to two alternative histomorphologic classifications: World Health Organization (WHO) or endometrial intraepithelial neoplasia (EIN) system. The 2017European Society of Gynaecological Oncology guidelines recommend paired box 2 protein (PAX2) immunohistochemistry to identify precancerous EH. However, methods for interpreting immunostaining and diagnostic accuracy are not defined, and the role of PAX2 in endometrial carcinogenesis is unclear. We aimed to assess: (a) PAX2 expression throughout endometrial carcinogenesis, from normal endometrium to benign EH, precancerous EH, and endometrial cancer (EC); (b) the diagnostic accuracy of PAX2 immunohistochemistry in diagnosing precancerous EH, defining criteria for its use. Material and methods:Electronic databases were searched for from their inception to July 2018. All studies evaluating PAX2 immunohistochemistry in normal endometrium, EH, and EC were included. Univariate comparisons of PAX2 expression were performed with Fisher's exact test (significant P < .05). Sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio (DOR), and area under the curve on summary receiver operating characteristic curves were calculated. Subgroup analyses were based on expression thresholds (decrease vs complete loss) and classifications used (WHO vs EIN). Results:Six studies with 266 normal endometrium, 586 EH, and 114 EC were included. Both decrease and complete loss of PAX2 expression were significantly more common in EC and precancerous EH than benign EH. Diagnostic accuracy was moderate for both PAX2 complete loss and decrease (areas under the curve 0.829 and 0.876, respectively). PAX2 complete loss with EIN system showed the best results (sensitivity = 0.72; specificity = 0.95; DOR = 43.13).Conclusions: PAX2 seems to behave as a tumor suppressor in endometrial carcinogenesis. PAX2 is an accurate marker of precancerous EH; complete loss of PAX2 and EIN classification appear as the optimal diagnostic criteria. K E Y W O R D Sbiomarker, cancer precursor, endometrial hyperplasia, endometrial intraepithelial neoplasia, endometrioid adenocarcinoma, paired box 2 protein Key message PAX2 loss is an accurate diagnostic marker of endometrial precancer. A complete loss of PAX2 and the EIN classification appear as the optimal diagnostic criteria.

show abstract

“…PAX2 is a downstream gene in the steroid hormone receptor signal pathway and is overexpressed in endometrial cancer and benign endometrial hyperplasia compared with normal controls [12]. PAX2 expression was also found to increase as the pathological malignancy progressed [13]. In a xenotransplanted tumor model of human endometrial cancer in nude mice, increased PAX2 expression was observed in tumors with poor cell differentiation, and tumor volume as well as expression of PCNA and Bcl-2 were decreased following knockdown of PAX2 [14].…”

Section: Introductionmentioning

confidence: 99%

DNA methylation promotes paired box 2 expression via myeloid zinc finger 1 in endometrial cancer

Nan

Wang

et al. 2016

Oncotarget

View full text Add to dashboard Cite

This work investigated the role of paired box 2 (PAX2) in endometrial cancer and its epigenetic regulation mechanism. Endometrial cancer tissues and cell lines exhibited increased PAX2 expression compared with hyperplasia, normal endometrium and endometrial epithelial cells. Knock-down of PAX2 resulted in reduced cell viability, invasion and migration, and PAX2 overexpression caused the opposite effects. Increased methylation of the PAX2 promoter was observed in both cancer tissues and cell lines and was positively correlated with PAX2 expression. After 5-Aza-CdR treatment, PAX2 mRNA and protein were down-regulated, and PAX2 methylation was decreased. Deletion analysis confirmed that a repressive transcriptional regulatory region of the PAX2 promoter coincided with the hypermethylated region identified in MassARRAY analysis. Binding sites of myeloid zinc finger 1 (MZF1) are predicted in the defined region. Knock-down of MZF1 up-regulated the transcriptional activity and protein level of PAX2 after 5-Aza-CdR treatment, which indicated that MZF1 may act as a repressive transcription factor when the PAX2 promoter is unmethylated. In conclusion, PAX2 is involved in the carcinogenesis of endometrial cancer by stimulating cell growth and promoting cell motility. The overexpression of PAX2 in endometrial cancer is regulated by promoter hypermethylation and the transcription factor MZF1.

show abstract

Expression pattern of PAX2 in hyperplastic and malignant endometrium

Cited by 15 publications

References 29 publications

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

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

PAX2 in endometrial carcinogenesis and in differential diagnosis of endometrial hyperplasia: A systematic review and meta‐analysis of diagnostic accuracy

DNA methylation promotes paired box 2 expression via myeloid zinc finger 1 in endometrial cancer

Contact Info

Product

Resources

About