BMC Cancer 2006, 6:10 http://www.biomedcentral.com/1471-2407/6/10 Cytokeratin 8/18 expression Cytokeratin 19 expression 1,0 s ie0,8 t i l i b a b o r0,6 p l a v i v r s0,4 u e v i t a l u m0,2 u c 0,0 p<0.04 Ck 8/18 negative Ck 8/18 positive 1,0 s ie0,8 t i l i b a b o r0,6 p l a v i v r s0,4 u e v i t a l u m0,2 u c 0,0 p<0.01 Ck 19 negative Ck 19 moderate Ck 19 high level 0 20 40 60 Overall survival (month) 80 100 0 20 40 60 80 Overall survival time (month) 100 itFOnhivegdeueKrpraaelplnls2aduner-nvMciveailoeornfmCpeaytioheoknedtrwatiitnh 8o–r1a8lseqxuparmeossuiosnceclallcaurlactineodmbya Overall survival of patient with oral squamous cell carcinoma in dependence on Cytokeratin 8–18 expression calculated by the Kaplan-Meier method. itFOnhivegdeueKrpraaelplnls3aduner-nvMciveaileoornfmCpeayttihoeokndetrwatitinh o19raelxsqpureasmsioounsccaellcluclartecidnobmya Overall survival of patient with oral squamous cell carcinoma in dependence on Cytokeratin 19 expression calculated by the Kaplan-Meier method. Fig. 2) and a significant decreased overall survival associ- ated with increased expression level of CK 19 (CK 19< 1% (n = 149), Ck 19 = 1–49% (n = 96), Ck 19 >50% (n = 11), p < 0.01, Fig. 3) In the subgroup of node negative oral squamous cell can- cer the expression of Ck 8/18 and the high expression of Ck 19 were also correlated with a poor overall survival (Ck 8/18, p < 0,04, Fig. 4) (Ck 19, p < 0.01). No influence of vimentin coexpression on the overall survival prognosis of Ck 8/18 and Ck 19 positive carcinomas was observed. All carcinomas with an expression of Ck 8/18 and Ck 19 were reviewed and re-evaluated on whole sections. This was done in order to exclude the possibility of a misinter- pretation and misclassification of dedifferentiated salivary gland carcinomas as poorly differentiated SCC's. How- ever, in all these tumours the diagnosis of a primary sali- vary gland carcinoma could be ruled out. In multivariate Cox analysis we compared the overall sur- vival according to clinically established prognostic factors tumour size and nodal status with the expression of Ck 8/ 18, Ck 5/6, Ck 1, CK 10, Ck 14 and Ck 19 (Table 5). Three parameters as nodal status, tumour size and Ck 8/18 expression were indicated by Cox regression as independ- ent predictors of survival prognosis. Discussion Intermediate filaments are central components of the intracellular skeleton. The expression of distinct interme- diate filament proteins is tissue-specific and almost highly conserved during carcinogenesis. Intermediate filaments are interpreted as mere bystanders and markers of distinct intracellular, cell-specific regulation mechanisms. Several studies associated changes in intermediate filament expression with an altered cellular behaviour [17,18]. The expression of high molecular weight cytokeratins, especially Ck 5 is a hallmark of squamous epithelium and is predominantly seen in the basal layers of stratified epi- thelium [2,19]. This cell layer is regarded as the anatomi- cal localization of tissue specific stem/progenitor cells. Stem cells of stratified epithelium have been repeatedly described as the major cellular targets for cancer causing mutations and therefore might give in a long term rise to the development of SCC's. In the context of the existing literature it seems logical that SCC's retain and are pheno- Page 5 of 8 (page number not for citation purposes)