Thymidine kinase 1 (TK1) is a key
enzyme involved in the synthesis of
DNA precursors and thus, cell proliferation-dependent.
Antibodies against TK1 have provided attractive tools for
cancer diagnosis. Expression of TK1 in 158
non-small cell lung cancer (NSCLC) patients with 59
adenocarcinoma (AC) and 99
squamous cell carcinoma (SCC) was determined by anti-TK1
monoclonal antibody (mAb) 1E3 (AC, n=50; SCC, n=70). Parallel
tumor sections were stained for Ki-67 (MIB-1), and TK1 expression was also investigated with anti-TK1 chicken
IgY Ab (AC, n=9; SCC, n=29; normal lung tissues, n=10). In one AC and one SCC patient, gene profiling was done by
cDNA array. Using the mAb 1E3, a significantly higher TK1 labeling index (LI) of AC patients was found (68%) compared to the LI of Ki-67 (36%). This difference was due to a significantly higher TK1 LI of
tumor stage II and grade 2. Although no difference in the LI of TK1 and Ki-67 of SCC patients was found (54 vs. 53%), significantly higher TK1 LI of SCC patients of
tumor grade 1 was found. Using the anti-TK1
IgY Ab, a higher TK1 LI of AC patients (78%) and SCC patients (66%) was found compared to staining with mAb 1E3 (68 vs. 54%), but it was not significantly different. Samples stained only for TK1 represented mostly
tumor stages I and II and grades 1 and 2 of both AC and SCC. AC patients whose samples stained only for Ki-67 were found to be in stage I and grade 1.
cDNA profiling showed that the expression of BRCA1,
cyclin B1 and cdc2p34 was higher in AC compared to SCC, while the expression of
IGFBP-3 and EGFR was higher in SCC. TK1 is apparently a more reliable marker in AC patients than Ki-67. However, a combination of the two markers may help identify patients of different stages and grades more efficiently, and
cyclin/
kinase complexes and
growth factors/receptors may be useful markers in distinguishing AC from SCC.