Increased expression of SKP2 and phospho-MAPK/ERK1/2 and decreased expression of p27 during tumor progression of cervical neoplasms.
OBJECTIVE
The objective of this study was to investigate whether the expression of SKP2, p27 and phospho-MAPK/ERK1/2 is associated with the progression of human cervical neoplasia.


METHODS
We performed immunohistochemical detection to stain formalin-fixed paraffin-embedded cervical tissues with anti-SKP2 and anti-p27 monoclonal antibodies and anti-phospho-p42/44 MAPK antibody. The study sample included 23 normal cervical epithelium, 25 low-grade squamous intraepithelial lesion (LSIL), 19 high-grade squamous intraepithelial lesion (HSIL), and 31 squamous cell carcinomas (SCC). In addition, 14 frozen cervical biopsies, including 1 normal, 6 HSIL, 2 adenocarcinoma and 5 SCC, and a human cervical cancer cell line (HeLa), were analyzed the expression levels of mRNA and protein of SKP2 and p27 by RT-PCR and Western blot analysis, respectively.


RESULTS
The expression of SKP2, p27 and phospho-MAPK/ERK1/2 were strongly associated with cervical neoplastic progression (P<0.0001, P=0.006, P=0.003, respectively; Fisher's Exact Test). In addition, SKP2 expression was positively correlated with phospho-MAPK/ERK1/2 expression (Spearman correlation coefficient=0.480, P=0.0002). The association between SKP2 and phospho-MAPK/ERK1/2 was significant after controlling for the four histologic grades (P=0.038, Mantel-Haenszel test).


CONCLUSIONS
These results suggest that expression levels of SKP2, p27 and phospho-MAPK/ERK1/2 may serve as markers for progression in human cervical carcinoma and may also play roles in cervical carcinoma progression and cervical carcinogenesis.
Chen
Tzu-Ping
TP
Department of Pathology, E-DA Hospital, Kaohsiung, Taiwan.
Chen
Chien-Ming
CM
Chang
Hsueh-Wen
HW
Wang
Jyh-Seng
JS
Chang
Wei-Chi
WC
Hsu
Su-In
SI
Cho
Chung-Lung
CL
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009367:Neoplasm Staging; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044786:S-Phase Kinase-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D012333:RNA, Messenger; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases