p16INK4a and p21Waf1/Cip1 expression correlates with clinical outcome in vulvar carcinomas.
OBJECTIVE
Aberrant expression of the cell cycle kinase inhibitors p16, p21, and p27 has been associated with poor prognosis in a variety of human malignancies. Little is known, however, about their clinical impact in vulvar carcinoma patients. Thus, we analyzed a larger series of vulvar squamous cell carcinomas and compared the results with clinical outcome.


METHODS
A total of 224 vulvar squamous cell carcinomas were immunohistochemically investigated for expression of p16, p21, and p27 using the biotin-streptavidin-peroxidase method and the OptiMax Plus automated cell staining system.


RESULTS
High p16 (> or =5%) positive nuclear immunostaining was found in 69 (31%) cases, high p21 (any staining) protein levels was detected in 95 (42%) cases, and low p27 (< or =50% positive nuclei) staining was seen in 170 (76%) cases. High expression of p16 was related to lower patient age and low expression of p53. High expression of p16 indicated a better prognosis in the multivariate analysis (RR = 0.5, 95% CI = 0.2-1.0) and less risk of developing lymph node metastasis (OR = 0.3, 95% CI = 0.2-0.7). High level of p21 was significantly associated with shorter survival in patients staged FIGO I and II (RR = 3.4, 95% CI = 1.3-9.3). We found no significant correlation between the expression of p27 and any of the clinicopathological variables.


CONCLUSIONS
Our study indicates a prognostic relevance for p16 and p21 immunoreactivity. Low level of p16 protein and high level of p21 protein were associated with a shorter disease-related survival. We did not find p27 protein expression to be useful as a prognostic indicator in vulvar carcinoma patients.
Knopp
Synne
S
Department of Pathology, The Norwegian Radium Hospital, University of Oslo, 0310 Oslo, Norway. synne.nopp@klinmet.uio.no
Bjørge
Tone
T
Nesland
Jahn M
JM
Tropé
Claes
C
Scheistrøen
Marit
M
Holm
Ruth
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D014846:Vulvar Neoplasms / Q000378:metabolism* / Q000473:pathology
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27