Loss of cyclin D1 and p16 expression correlates with local recurrence in nasopharyngeal carcinoma following radiotherapy.
BACKGROUND
The cyclin D1/p16/Rb pathway plays a critical role in tumorigenesis and each component of this pathway may be affected in various malignancies. The purpose of this study was to investigate the expression and prognostic significance of these proteins in nasopharyngeal carcinoma (NPC).


METHODS
Sixty-five patients undergoing radiotherapy for NPC were analyzed. The expression of cyclin D1, p16 and pRb was evaluated with immunohistochemical analysis of archived pretreatment tumor materials and expression of these proteins was correlated with clinicopathological parameters.


RESULTS
Positive expression of cyclin D1 was observed in 43 of 65 NPCs (66%). p16 and pRb inactivation was identified in 42 of 65 (65%) and four of 65 (6%) tumors, respectively. All but seven tumors (58 of 65, 89%) contained at least one alternation in the cyclin D1/p16/Rb pathway. Loss of cyclin D1 as well as p16 was closely related to local recurrence after radiotherapy for NPC (P = 0.015 and 0.047). No association between pRb expression and clinicopathological outcome was apparent.


CONCLUSIONS
The study's results suggest that the cyclin D1/p16/Rb pathway plays an important role in NPC tumorigenesis. We also find that cyclin D1 and p16 protein levels in NPC may be of use clinically as a predictor of local tumor control.
Hwang
C-F
CF
Department of Otolaryngology, Chang-Gung University, Chang-Gung Memorial Hospital, Kaohsiung, Taiwan.
Cho
C-L
CL
Huang
C-C
CC
Wang
J-S
JS
Shih
Y-L
YL
Su
C-Y
CY
Chang
H-W
HW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000378:metabolism*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D019938:Cyclin D1