Cytokeratin 17 mRNA expression has potential for diagnostic marker of oral squamous cell carcinoma.
OBJECTIVE
Determination of marker for identification of oral squamous cell carcinoma (OSCC) is important for early diagnosis and individual therapy. Cytokeratins (CKs) like CK 19 and CK 20 are known to be useful diagnostic and prognostic markers for solid tumors. The aim of this study was to evaluate the relevance of further CKs for diagnosis of OSCC.


METHODS
In 10 OSCC and 5 normal mucosal samples, the expression patterns of 31 CK genes were examined by cDNA microarray in order to identify CKs with most pronounced over-expression. The results were verified for CK 17, CK 19, and CK 20 in addition to 46 OSCC samples by relative quantification (RQ) using SYBR green real-time reverse transcriptase polymerase chain reaction (RT qPCR). A correlation of the CK expressions with the tumor classification was carried out.


RESULTS
cDNA microarray analyses showed that out of all CKs, CK 17 was up-regulated strongest in OSCC compared to normal samples, and over-expression was most significantly associated with diagnosis (P = 0.002). Expression rates of CK 19 and CK 20 were not significantly different between OSCC samples and normal samples. In 56 samples analyzed by real-time RT qPCR, CK 17 was over-expressed in 53 (94.6%), CK 19 in 18 (32.1%), and CK 20 in 7 (12.5%). The over-expression of CK 17 was significantly associated with metastases of neck lymph nodes (P < 0.05). CK 19 was significantly over-expressed in T3 and T4 OSCC, in stage III and IV patients (P < 0.05), and in poorly differentiated OSCC (P < 0.03). The over-expression of CK 20 was significantly associated with metastases of neck lymph nodes (P < 0.03). Determined by RQ, the mean value of CK 17 over-expression was significantly higher than that of the other CKs (P < 0.01), and was significantly associated with T1 and T2 OSCC (P < 0.03) and with stage I and II patients (P < 0.01).


CONCLUSIONS
CK 19 might be linked to the clinical progression and differentiation of OSCC, and CK 20 could be associated with metastases of neck lymph nodes in OSCC. Due to the significant up-regulation and the strong over-expression, CK 17 might be the most suitable marker for diagnosis of OSCC out of the CK-family.
Toyoshima
Takeshi
T
Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Glueckstrasse 11, 91054 Erlangen, Germany.
Vairaktaris
Eleftherios
E
Nkenke
Emeka
E
Schlegel
Karl Andreas
KA
Neukam
Friedrich Wilhelm
FW
Ries
Jutta
J
D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D053537:Keratin-17 / Q000235:genetics*; D053539:Keratin-19 / Q000235:genetics; D053554:Keratin-20 / Q000235:genetics; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction