The relationship between cyclin B1 overexpression and lymph node metastasis in human colorectal cancer.
BACKGROUND
Although the molecular and biologic changes in G1/S cyclins have been well characterized, alterations in G2/M cyclin and its possible roles in cell proliferation and metastatic behavior remain to be elucidated.


METHODS
The cyclin B1 expression immunohistochemically determined in 109 patients with colorectal cancer was investigated from the standpoints of tumor invasion, lymph node metastasis, and prognosis. These findings were analyzed in relation to the growth fractions determined with Ki-67 and proliferating cell nuclear antigen and to the expression of p53 protein.


RESULTS
A positive cyclin B1 expression was found in 62 (56.8%) of 109 patients. Tumors with cyclin B1 overexpression did not involve any lymph node, did not permeate the lymphatics, did not invade the blood vessels, and tended to be of Dukes' stage B. Those characterized by a lower expression of cyclin B1 protein frequently metastasized to the lymph nodes, showed lymphatic permeation or vessel invasion, and tended to be of Dukes' stages C or D. The overexpression of cyclin B1 showed no significant correlation with proliferative activities determined by means of Ki-67 or proliferating cell nuclear antigen or with the expression of p53 protein. Although the cyclin B1-positive group seemed to survive longer in comparison with the cyclin B1-negative group, the difference was not statistically significant. In a logistic regression analysis the cyclin B1 expression proved to be a significant factor related to the occurrence of lymph node metastasis, as did tumor size and curability of disease.


CONCLUSIONS
These findings suggest a close correlation between a lack of cyclin B1 immunostaining and a stronger metastatic behavior in colorectal cancer. This inverse relationship was not ascribed to a mere consequence of cell proliferation but rather to organ specificity, heterogeneity, or an uncontrolled cyclin B1 expression probably caused by the deregulation of G2/M transition.
Korenaga
Daisuke
D
Fukuoka Dental College and the Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takesue
Fumio
F
Yasuda
Mitsuhiro
M
Honda
Masayuki
M
Nozoe
Tadahiro
T
Inutsuka
Sadaaki
S
D000368:Aged; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000556:secondary*; D019926:Cyclin B / Q000032:analysis / Q000096:biosynthesis*; D056744:Cyclin B1; D005260:Female; D016195:G2 Phase; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis; D008297:Male; D008938:Mitosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53