OBJECTIVE: This study aimed to analyze the expression pattern of glycogen synthase kinase 3β (GSK3β) and its phosphorylated forms, GSK3β phosphorylated at Ser9 (pS9GSK3β), and GSK3β phosphorylated at Tyr216 (pY216GSK3β), in cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC). METHODS: We performed immunohistochemical staining for GSK3β, pS9GSK3β, and pY216GSK3β in 64 SCC and 20 AC cases and compared their expression patterns between the 2 tumor types. RESULTS: Increased GSK3β and pS9GSK3β expression but decreased pY216GSK3β expression compared with that in the normal cervix were observed in both SCC and AC specimens. Specifically, the levels of GSK3β and pS9GSK3β were significantly increased in SCC and AC, respectively. GSK3β was localized in the nucleus and/or cytoplasm of SCC and AC cells. However, pS9GSK3β was predominantly localized in the membrane of AC cells, whereas it was present in the nucleus and/or cytoplasm of SCC cells. CONCLUSION: The results suggest that the phosphorylation status of GSK3β changes during cervical cancer development and the different expression levels and patterns of GSK3β and pS9GSK3β are associated with the specific histologic phenotype of cervical cancer.
Adenocarcinoma ; Carcinoma, Squamous Cell ; Cervix Uteri ; Cytoplasm ; Epithelial Cells ; Female ; Glycogen Synthase Kinases ; Membranes ; Phenotype ; Phosphorylation ; Uterine Cervical Neoplasms

Background: We sought to determine whether lipopolysaccharide binding protein (LBP), pentraxin 3, resistin, and insulin-like growth factor binding protein (IGFBP)-3 in plasma and amniotic fluid (AF) can predict microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI in women with preterm premature rupture of membranes (PPROM). Methods: This was a retrospective cohort study involving 168 singleton pregnant women with PPROM. AF obtained via amniocentesis was cultured and assayed for interleukin (IL)-6 to define IAI and for IL-8 to compare with AF biomarkers. Plasma samples were collected at the time of amniocentesis, and C-reactive protein (CRP) levels in serum were compared with plasma biomarkers. The stored plasma and AF samples were assayed for LBP, pentraxin 3 (PTX3), resistin, and IGFBP-3 by ELISA. Results: Multivariate logistic regression analysis revealed that: 1) elevated plasma and AF levels of LBP were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 2) elevated AF, but not plasma, PTX3, and resistin levels were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 3) decreased IGFBP-3 levels in the plasma were independently associated with only IAI, whereas those in the AF were associated with only microbial-associated IAI. Among the tested biomarkers, AF PTX3 and resistin had the highest predictive performance for MIAC, IAI, and microbial-associated IAI (area under the curves [AUC] = 0.85–0.95), which is similar to the performance of AF IL-8. The AUCs of the plasma LBP and IGFBP-3 were similar to that of serum CRP with respect to IAI. Conclusion Maternal plasma LBP and IGFBP-3 are potential biomarkers for the non-invasive identification of IAI in women with PPROM, with a similar accuracy to the serum CRP level.AF LBP, PTX3, resistin, and IGFBP-3 may be involved in the intra-amniotic inflammatory responses in PPROM complicated by MIAC.