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Open AccessArticle

Pyruvate Kinase M2 Expression: A Potential Metabolic Biomarker to Differentiate Endometrial Precancer and Cancer that is Associated with Poor Outcomes in Endometrial Carcinoma

1
Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
2
Department of Obstetrics and Gynecology, Tri-Service General Hospital, Magong City 88056, Penghu Branch, Taiwan
3
School of Public Health, National Defense Medical Center, Taipei 114, Taiwan
4
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
5
Department of Obstetrics and Gynecology, Chiayi Chang Gung Memorial Hospital, Chiayi 600, Taiwan
6
Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 800, Taiwan
7
Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Environ. Res. Public Health 2019, 16(23), 4589; https://doi.org/10.3390/ijerph16234589
Received: 6 October 2019 / Revised: 15 November 2019 / Accepted: 19 November 2019 / Published: 20 November 2019
(This article belongs to the Special Issue Global Women's Health)
Background: Pyruvate kinase M2 (PKM2) is a regulator of the processes of glycolysis and oxidative phosphorylation, but the roles that it plays in endometrial cancer remain largely unknown. This study evaluated the PKM2 expression in normal endometrium, endometrial hyperplasia, and endometrial carcinoma, and its prognostic value was investigated in endometrial carcinoma patients. Methods: A hospital-based retrospective review was conducted to examine the immunohistochemical PKM2 distribution in 206 endometrium samples from biopsies or hysterectomies. The immunoreactivity of PKM2 was divided into groups of low and high scores according to the extent and intensity of staining. Results: Intense cytoplasmic staining was observed for the PKM2 protein in malignant endometrial lesions. A high PKM2 score was observed in many endometrial carcinoma samples (50.0%), but there was a low percentage in endometrial atypical hyperplasia (12.5%). High PKM2 expression was not found in the normal endometrium (0.0%) nor endometrial hyperplasia without atypia (0.0%). The PKM2 protein score was significantly higher in endometrial carcinoma samples than premalignant endometrial lesions (p < 0.001). Notably, higher PKM2 scores in cases of endometrial carcinoma correlated with poor overall survival (p = 0.006), and the hazard ratio for death was 3.40 (95% confidence interval, 1.35–8.56). Conclusions: Our results indicate that the prevalence of PKM2high tumor cells in endometrial carcinoma is significantly associated with worse prognostic factors and favors a poor prognosis. The expression of PKM2 is also a potential histopathological biomarker for use in the differential diagnosis of malignant and premalignant endometrial lesions. View Full-Text
Keywords: pyruvate kinase M2; endometrial hyperplasia; endometrial carcinoma pyruvate kinase M2; endometrial hyperplasia; endometrial carcinoma
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Lai, Y.-J.; Chou, Y.-C.; Lin, Y.-J.; Yu, M.-H.; Ou, Y.-C.; Chu, P.-W.; Wu, C.-C.; Wang, Y.-C.; Chao, T.-K. Pyruvate Kinase M2 Expression: A Potential Metabolic Biomarker to Differentiate Endometrial Precancer and Cancer that is Associated with Poor Outcomes in Endometrial Carcinoma. Int. J. Environ. Res. Public Health 2019, 16, 4589.

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