Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients.
Cyclin B1, identified as a regulator of late cell cycle, is involved in the development and progression of a variety of human malignancies. To clarify the role of cyclin B1 in the pathogenesis and prognosis of renal cell carcinoma (RCC), protein expression was compared with clinicopathological characteristics of patients as well as the long-term survival after surgical therapy. Expression analysis was carried out by immunohistochemistry and tissue microarray analysis. The microarrays that represented the primary tumors, their invasion front and normal peritumoral renal parenchyma contained 753 tissue cores obtained from 251 randomly selected nephrectomy specimens. Immunopositivity within the primary tumors was significantly associated with tumor stage (pT) (p < 0.01), lymph node status (pN) (p < 0.01) as well as the presence of systemic metastatic disease (p = 0.01). Subcellular expression in the cytoplasm of tumor cells significantly correlated with pT (p = 0.02) and pN (p = 0.03). When peritumoral tissue samples exhibited a relative amount of <10% of positively reacting epithelial cells, cyclin B positivity was identified to predict long-term survival of patients in univariate analysis (p < 0.01) whereas borderline significance was observed in multivariate statistical analysis (p = 0.05). Increased intratumoral cyclin B1 positivity and aberrant localization of signals within the cytoplasm of tumor cells is positively correlated with the tendency towards tumor progression, indicating the significant role of cyclin B1 in the development and pathogenesis of RCC. The result of uni- and multivariate statistical analysis suggests the prognostic value of cyclin B1 for RCC patients.
Department of Urology, Medizinische Hochschule Hannover, Hannover, Germany.
Stephen O
SO
Ikuerowo
Markus A
MA
Kuczyk
Michael
M
Mengel
Eyck
E
van der Heyde
Olayiwola B
OB
Shittu
Bernhard
B
Vaske
Udo
U
Jonas
Stefan
S
Machtens
Jürgen
J
Serth
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology*; D019926:Cyclin B / Q000378:metabolism*; D056744:Cyclin B1; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D013347:Subcellular Fractions / Q000378:metabolism; D015996:Survival Rate
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1