Expression of p16INK4a and MIB-1 in relation to histopathology and HPV types in cervical adenocarcinoma.
A total of 101 primary cervical adenocarcinomas were analyzed for the presence of p16INK4a and MIB-1 expression in correlation with the presence of 'high-risk' types of human papillomavirus (HR-HPV) and clinical outcome. We found that adenocarcinoma grading showed a significant negative correlation to p16INK4a levels (p=0.001): i.e. we found less intense p16 staining in poorly differentiated tumors than in more highly differentiated tumors as well as a highly significant correlation between HPV infection and higher levels of p16INK4a staining (p=0.00), which was similar for different HPV-types. Tumor suppressor protein p16INK4a levels were higher in HPV positive than in HPV negative tumors. Higher levels of the proliferation marker MIB-1 were associated with poorer outcome. Higher MIB-1 levels were seen in tumors with a lower grade and higher stage at diagnosis. Moreover, MIB-1 levels seem to be higher in tumors due to infection with HPV 16 and 18 compared with HPV 45. MIB-1 may be a helpful marker in grading adenocarcinoma: a high level of expression of MIB-1 indicates a low grade of tumor, whereas high expression of p16INK4a indicates a highly differentiated of the tumor. Thus, immunostaining for p16INK4a appears to be a useful diagnostic tool for cervical adenocarcinoma.
Muller
Susanne
S
Department for Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska University Hospital at Huddinge, Karolinska Institutet, S-141 86 Stockholm, Sweden.
Flores-Staino
Carmen
C
Skyldberg
Barbro
B
Hellström
Ann-Cathrin
AC
Johansson
Bo
B
Hagmar
Bjorn
B
Wallin
Keng-Ling
KL
Andersson
Sonia
S
D000230:Adenocarcinoma / Q000150:complications* / Q000821:virology*; D000328:Adult; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008875:Middle Aged; D027383:Papillomaviridae / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000150:complications*; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000150:complications* / Q000821:virology*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen