Reduction of p12DOC-1 expression is a negative prognostic indicator in patients with surgically resected oral squamous cell carcinoma.
OBJECTIVE
p12DOC-1 is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities. Expression of p12DOC-1 is reduced and/or lost in tumor tissues. The purpose of this study is to correlate in vivo the expression of p12DOC-1 in oral cancer tissues by immunohistochemistry with clinical and pathological parameters.


METHODS
Twenty-five cases of normal oral mucosa and 127 cases of oral squamous cell carcinomas were evaluated. Patients' charts were reviewed for clinical, pathological, and 10-year survival data. Because p12DOC-1 is a growth suppressor and associates with CDK2, parallel immunostaining was done for proliferating cell nuclear antigen and CDK2 to evaluate cell proliferation and potential correlation with CDK2.


RESULTS
Our results showed that strong p12DOC-1 staining was uniformly seen in normal oral mucosa. p12DOC-1 staining was reduced or absent in 81 cases (63.8%) of oral squamous cell carcinomas. Decreased p12DOC-1 staining (<25% of cells stained) correlated with tumor mode of invasion (P = 0.001) and higher proliferating cell nuclear antigen (P = 0.0028) and CDK2 (P = 0.0020) expression. Survival analysis showed significant correlation of low p12DOC-1 expression with the risk of cervical lymph node metastasis (P = 0.001) and patients' 10-year survival status (P = 0.0214).


CONCLUSIONS
These results allow us to conclude that reduction of p12DOC-1 protein expression is a frequent event in oral cancers. Intratumor immunohistochemical evaluation of p12DOC-1 expression can be an adjunctive prognostic indicator for patients with oral cancer.
Shintani
S
S
Laboratory of Molecular Pathology, Division of Oral Pathology, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Mihara
M
M
Terakado
N
N
Nakahara
Y
Y
Matsumura
T
T
Kohno
Y
Y
Ohyama
H
H
McBride
J
J
Kent
R
R
Todd
R
R
Tsuji
T
T
Wong
D T
DT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D015331:Cohort Studies; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000032:analysis; D004848:Epithelium / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins
C096151:CDK2AP1 protein, human; D018809:Proliferating Cell Nuclear Antigen; D025521:Tumor Suppressor Proteins; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases