Immunohistochemical expression of cyclin E in endometrial adenocarcinoma (endometrioid type) and its clinicopathological significance.
OBJECTIVE
Cyclin E is known as a G1-S phase regulatory protein and its abnormal expression has been implicated in cellular proliferation. This study aimed to investigate the correlation of cyclin E expression with tumorigenesis of the endometrium, proliferative activity, and clinicopathological features of endometrial adenocarcinoma.


METHODS
Immunohistochemical staining for cyclin E in addition to cyclin-dependent kinase 2 (cdk2), Ki67, p27, and p53 was performed by the labeled streptavidin-biotin method on formalin-fixed, paraffin-embedded tissues of normal endometria (20 cases), endometrial hyperplasias (20 cases), and endometrial adenocarcinomas (endometrioid type) (127 cases). Positive staining was expressed as a labeling index (LI) based on percentages of positive nuclei in tumor cells.


RESULTS
Immunohistochemistry showed that the nuclei of the cells were positive for cyclin E. Both proliferative and secretory endometria, and endometrial hyperplasia regardless of type were negligible for cyclin E expression. The expression in normal endometrium and hyperplasia was significantly less than that in endometrial adenocarcinomas (P<0.0001). LIs of cyclin E in well-differentiated, moderately differentiated, and poorly differentiated endometrial adenocarcinomas were 31.5+/-33.3%, 37.8+/-31.9%, and 51.1+/-30.8%, respectively. Cyclin E expression increased significantly more in histological grades. The LI of cyclin E in carcinoma was positively correlated with that of cdk2, Ki67, and p53 but not with p27. The cyclin E expression was correlated with myometrial invasion and lymph-vascular space involvement, but not with FIGO stage, lymph node metastasis, coexisting endometrial hyperplasia, estrogen receptor, progesterone receptor, and menopause.


CONCLUSIONS
Cyclin E as a complex with cdk2 is associated with carcinogenesis and disease progression in endometrial adenocarcinoma, and might be a prognostic indicator of endometrial adenocarcinoma.
Kato
N
N
Department of Clinical Cytology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan.
Watanabe
J
J
Jobo
T
T
Nishimura
Y
Y
Fujisawa
T
T
Kamata
Y
Y
Kuramoto
H
H
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019927:Cyclin E / Q000032:analysis*; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000032:analysis; D008875:Middle Aged; D009124:Muscle Proteins; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D019927:Cyclin E; D008840:Microfilament Proteins; D009124:Muscle Proteins; C058992:Tagln protein, mouse; D016159:Tumor Suppressor Protein p53