Expression of p21WAF1/CIP1 in adenocarcinoma of the uterine cervix: a possible immunohistochemical marker of a favorable prognosis.
BACKGROUND
The purpose of this study was to assess the prognostic significance of the expression of estrogen receptor and cell cycle regulatory gene products in cervical adenocarcinoma.


METHODS
In 40 cases of adenocarcinoma of the uterine cervix and 10 normal cervices, expression of estrogen receptor and cell cycle regulatory gene products (cyclin E, p16, p21WAF1/CIP1, p27, p53, and Ki-67) was studied using immunohistochemical techniques. The survival of the patients was analyzed in terms of such variables as the expression of these molecules in the tumor and conventional clinicopathologic features, and the Cox proportional hazards model was used to predict the survival of patients with cervical adenocarcinoma.


RESULTS
Expression of estrogen receptor was consistently observed in normal cervical glands, but in cervical adenocarcinoma it was lost (in 28 cases) or significantly diminished (in 12 cases). Normal cervical glandular cells were usually negative for the cell cycle regulatory gene products, whereas 47.5-85% of cervical adenocarcinomas were positive for these molecules. When the expression of these molecules was analyzed, significant positive correlations were found between p16 and p27, cyclin E and p27, and cyclin E and p21WAF1/CIP1. Univariate survival analysis revealed that the presence of parametrial invasion, the presence of lymph node metastasis, negative staining for p21WAF1/CIP1, and a moderately or poorly differentiated tumor all correlated significantly with a poor prognosis. In a stepwise regression analysis, the expression of p21WAF1/CIP1 and negative pelvic lymph nodes were the best predictors of a favorable prognosis.


CONCLUSIONS
Expression of p21WAF1/CIP1 correlated with a favorable prognosis for patients with cervical adenocarcinoma and may serve as a useful marker of survival in cases of this disease.
Lu
X
X
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan.
Toki
T
T
Konishi
I
I
Nikaido
T
T
Fujii
S
S
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D018816:Genes, cdc; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27