Immunohistochemical analysis of major TGF-beta isoforms and their receptors in laryngeal carcinomas.

We analyzed immunohistochemically the tissue distribution of the three major transforming growth factors-beta isoforms (TGF-beta1, -2, -3) and their receptors (TBR-I, -II and -III) in tissue samples from 38 patients with laryngeal squamous cell carcinomas. Besides a qualitative evaluation, the number of the respectively labeled cells was determined by morphometric analysis. In all tumor samples a significant staining of most tumor cells was seen both for the TGF-beta isoforms and the TBRs. Similarly, the majority of stromal cells were labeled. On semiserial sections, there were only minor differences in the distribution pattern and in the number of labeled cells between the three TGF-beta isoforms and the TBRs, suggesting that most tumor cells are actively involved in the neosynthesis of TGF-betas and TBRs; accordingly, at least most tumor cells seem to be capable of producing more than one TGF-beta form and in parallel several TBRs. With decreasing tumor cell differentiation the number of TGF-beta- and TBR-positive tumor cells decreased slightly (but not to a statistically significant degree). Interestingly, the stromal cells were labeled for TGF-betas and TBRs to a lower extent than the epithelial cells, and there was no significant difference between non-tumor-associated control stroma and the immediate peritumoral stroma. Our observations suggest an even, enhanced level of TGF-beta production in laryngeal squamous cell carcinomas, which may explain some well-known side-effects of tumor growth, such as stromal desmoplasia. In addition, the presence of immunoreactive TBR-proteins in the vast majority of tumor cells excludes the mere absence of TBRs in those carcinomas as the cause for inappropriate TGF-beta function in the tumor cells. This in turn suggests that molecular alterations either of the TBR-proteins non-affecting the synthesis and turnover or downstream alterations of the TGF-beta signaling pathway may be main reasons for the loss of response of the tumor cells to the enhanced amounts of TGF-betas.