Abstract
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.
Highlights
Endometrial carcinoma (EC) is one of the most common gynecological cancers worldwide [1].According to statistics from the American Cancer Society, there were about 63,230 new cases of EC in2018, and 11,350 women died from it
We previously found that Pyruvate kinase M2 (PKM2) is overexpressed in cases of ovarian cancer, and inhibiting PKM2 using shikonin resulted in inhibited growth of ovarian cancer cells [12]
We performed analyses on endometrial tissue microarrays to evaluate without atypia, atypical hyperplasia (AH), and EC
Summary
Endometrial carcinoma (EC) is one of the most common gynecological cancers worldwide [1].According to statistics from the American Cancer Society, there were about 63,230 new cases of EC in2018, and 11,350 women died from it. Endometrial carcinoma (EC) is one of the most common gynecological cancers worldwide [1]. Endometrial hyperplasia (EH) is clinically significant because of the associated risk of progression to endometrioid EC, and atypical forms of EH are considered as premalignant lesions [2]. 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).
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