Expression of p27, p21, and p16 protein in early squamous cervical cancer and its relation to prognosis.
OBJECTIVE
To examine the prognostic significance of the protein expression of the cyclin-dependent kinase (cdk) inhibitors p27, p21, and p16 in early squamous cervical cancer (SCC).


METHODS
From 221 [corrected] patients who underwent radical hysterectomy and bilateral lymphadenectomy at our institution for stage IB SCC between 1987 and 1993, tissue blocks were available for this study. Immunohistochemistry using monoclonal antibodies against p27, p21, and p16 was used to examine protein expression. Ten patients who underwent hysterectomy for uterine prolaps served as controls.


RESULTS
p21 and p16 expression were increased in SCC and high expression was observed in 20% (44/221) and 43% (94/220) of tumors, respectively. p27 was decreased in SCC and low expression was found in 80% (177/221) of tumors. In univariate analysis all classical clinicopathological parameters were associated with prognosis. Low p16 expression was significantly related to decreased overall (P = 0.036) but not disease-free survival (P = 0.103). In multivariate analysis, deep stromal invasion but none of the cdk inhibitors was independently related to survival.


CONCLUSIONS
The cdk inhibitors p27, p21, and p16 are not independently associated with prognosis in stage IB SCC.
van de Putte
Gregg
G
Department of Gynecologic Oncology, The Norwegian Radium Hospital, Montebello, 0310, Oslo, Norway. gregg.marijke@pandora.be
Holm
Ruth
R
Lie
A Kathrine
AK
Tropé
Claes G
CG
Kristensen
Gunnar B
GB
D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; 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; D011379:Prognosis; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; 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