Cyclin D3 immunoreactivity is an independent predictor of survival in laryngeal squamous cell carcinoma.
OBJECTIVE
To analyze the prevalence and clinical relevance of cyclin D3 abnormalities in laryngeal squamous cell carcinoma (LSCC).


METHODS
Cyclin D3 immunoreactivity was evaluated in 223 formalin-fixed and paraffin-embedded samples of LSCC patients with a mean follow-up of 62.8 +/- 43.2 months. The occurrence of cyclin D3 extra signals was analyzed by fluorescence in situ hybridization in 47 randomly selected cases collected in a tissue microarray. Cyclin D1 immunoreactivity had been previously investigated in 133 cases.


RESULTS
Cyclin D3 immunoreactivity and gene extra signals were found in 39.5% and 42.6% of the cases, respectively, and the concordance between immunohistochemical and fluorescence in situ hybridization results was 70.2% (P = 0.0085). Cyclin D3 immunoreactivity was significantly associated with a high risk of death. Multivariate analysis showed that high tumor grade, exophytic/ulcerating tumor type, low performance status, and cyclin D3 immunoreactivity were the only independent predictors of poor overall survival. In the 133 cases analyzed for both cyclin D1 and cyclin D3, patients with cyclin D1+/cyclin D3+ tumors experienced the worst prognosis, patients with cyclin D1-/cyclin D3- exhibited the most prolonged survival, and with cyclin D1-/cyclin D3+ or cyclin D1+/cyclin D3- tumors an intermediate course was associated.


CONCLUSIONS
Our data suggest that cyclin D3 immunoreactivity, possibly due to the occurrence of gene extra copies, may represent an adjunct in LSCC patients' prognostication and contribute to identify D-type cyclins as potential targets of newly developed therapies.
Pruneri
Giancarlo
G
Division of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy. giancarlo.pruneri@ieo.it
Pignataro
Lorenzo
L
Valentini
Stefano
S
Fabris
Sonia
S
Maisonneuve
Patrick
P
Carboni
Nadia
N
Pece
Salvatore
S
Capra
Maria
M
Del Curto
Barbara
B
Neri
Antonino
A
Viale
Giuseppe
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D056743:Cyclin D3; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D013997:Time Factors; D016896:Treatment Outcome
C534696:CCND3 protein, human; D056743:Cyclin D3; D016213:Cyclins