Activated checkpoint kinase 2 expression and risk for oral squamous cell carcinoma.
BACKGROUND
Phosphoactivation of a DNA damage response molecule checkpoint kinase 2 (pChk2) may be a marker of oral epithelial cells that have entered the precancerous and squamous cell carcinoma (SCC) stages. We explored whether there was selective expression of pChk2 in precancerous lesions but not in nonneoplastic tissue of the oral mucosa.


METHODS
In a retrospective cohort design, 96 biopsied clinical leukoplakias and erythroplakias with known subsequent progression to SCC were identified from 48 subjects and assigned as the cases group. Expression status of pChk2 was compared with that of the 97 leukoplakias and erythroplakias that did not progress to SCC (control groups) by immunohistochemical analysis. Included in both groups were lesions with histologically confirmed dysplasia and those that lacked histologic evidence of atypia.


RESULTS
Subjects with pChk2-positive but histology-negative (for atypia) lesions had an 8.6 times higher risk of developing SCC compared with those with pChk2-negative and histology-negative lesions. Overall, the presence of detectable pChk2 staining was able to identify lesions at risk of developing SCC within 3 years with a sensitivity of 85.2%, specificity of 74.2%, and predictive accuracy of 78.2% (odds ratio, 19.9; 95% confidence interval, 7.3-55.5).


CONCLUSIONS
This is the first study to include histologically nonatypical cases in the analysis of a putative biomarker for oral precancerous lesions. Our data show that pChk2 merits further investigation as a promising biomarker that can discriminate those lesions at risk for developing SCC, regardless of histologic evidence for atypia.
Yoon
Angela J
AJ
College of Dental Medicine, Division of Oral and Maxillofacial Pathology, Columbia University Medical Center, 630 West 168th Street, PH15W-1562, New York, NY 10032, USA. ajk55@columbia.edu
Shen
Jing
J
Santella
Regina M
RM
Zegarelli
David J
DJ
Chen
Rongzhen
R
Weinstein
I B
IB
D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D064447:Checkpoint Kinase 2; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases