PMC1386691_01
Macroscopic, microscopic and immune histological appearance of an oral lichen planus and a subsequently arising squamous cell carcinoma. Macroscopic (A) and microscopic (B) picture of the squamous cells carcinoma. p53 expression (C to E, single positive cells are indicated by arrows), Erk 1/2 phosphorylation (F to H, increased expression is indicated by closed triangles) and Bax expression (I to K, reduced expression is indicated by open triangles) in mucosa before (C, F, I) and after (D, G, J) tacrolimus treatment, as well as in the arising squamous cell carcinoma (E, H, K); magnification: A 5x, C to K 20x. All lesions were obtained by surgical excision, fixed in formalin and embedded in paraffin. Five mum sections of tumor lesions were fixed in acetone and air dried for 30 min. Slides were incubated for 30 min with the indicated specific primary antibodies (anti-p53 [clone D07] and anti-Bax [polyclonal], DAKO, Hamburg, Germany; anti-pErk 1/2 [clone E10], Cell Signalling, BioLabs New England, Frankfurt, Germany) at predetermined dilutions ranging from 1:200 to 1:800.
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April 2005, the plaques on the left side of the tongue appeared increasingly compact and a biopsy specimen confirmed the suspected diagnosis of an oral squamous cell carcinoma (Figure 1A and 1B). After exclusion of systemic metastases, a combination of radiation and chemotherapy was initiated to be followed by surgery. Notably, retrospective analysis of the biopsy specimens revealed such accumulation of p53 over-expressing cells in small clusters (Figure 1C and 1D). In the present case, we actually observed an increased presence of phosphorylated Erk 1/2 within the mucosal epithelium after tacrolimus therapy (Figure 1F and 1G). Moreover, strong phosphoErk signals were obvious in the cells of the tongue carcinoma (Figure 1H). Bax (Figure 1E and 1I to 1K). Bax is a proapoptotic member of the Bcl-2 family and its transcription is directly regulated by p53; hence it may serve as a read out of p53 function. Strikingly, we observed a reduction of Bax expression in epithelial cells in some areas of tacrolimus treated mucosa and this reduction was also present in the carcinoma cells (Figure 1I to 1K).
Hypothetical effects of tacrolimus in keratinocytes promoting oncogenic transformation.
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Erk and p53) has been demonstrated (Figure 2).