Prognostic Significance of AMP-Dependent Kinase Alpha Expression in Cervical Cancer.
OBJECTIVE
Cervical cancer is one of the most common gynecological malignancies worldwide, and its association with the AMP-activated protein kinase (AMPK) is still unknown. We aimed to investigate the clinical correlation between AMPK expression and cervical cancer.


METHODS
The expression of AMPKα1, AMPKα2 and phosphorylated AMPKα (p-AMPKα) was determined immunohistochemically in 524 formalin-fixed, paraffin-embedded malignant and premalignant cervical tissues. Subsequently, associations with clinicopathological characteristics and patient survival were assessed.


RESULTS
AMPKα2 expression was observed in the cytoplasm and nucleus, while expression of AMPKα1 and p-AMPKα was mainly observed in the cytoplasm. p-AMPKα expression increased during the normal-to-tumor transition of cervical carcinoma (p < 0.001), but, once cancer developed, the expression of AMPKα2 and p-AMPKα decreased in large-sized tumors when compared to smaller tumors (36 vs. 68%, p = 0.004 and 39 vs. 64%, p = 0.029, respectively). Notably, AMPKα2 expression was significantly associated with better disease-free survival (HR 0.29, 95% CI 0.10-0.86, p = 0.026).


CONCLUSIONS
The AMPKα2 isoform showed potential as a favorable prognostic marker in cervical cancer. Therefore, additional studies are necessary to further clarify the complex contribution of AMPK isoforms and of phosphorylation status to cervical cancer progression and prognosis.
Experimental Pathology Laboratory, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Md., USA.
Chel Hun
CH
Choi
Joon-Yong
JY
Chung
Hanbyoul
H
Cho
Haruhisa
H
Kitano
Eileen
E
Chang
Kris
K
Ylaya
Eun Joo
EJ
Chung
Jae-Hoon
JH
Kim
Stephen M
SM
Hewitt
D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D014408:Biomarkers, Tumor; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*
D014408:Biomarkers, Tumor; D007527:Isoenzymes; C526181:PRKAA2 protein, human; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human