[The effect of the microenvironment of head and neck cancers on tumor progression].
In the last 20 years the incidence and mortality of head and neck squamous cell carcinomas showed an increasing rate in Hungary. In our work we examined the microenvironment of head and neck cancers localized in different anatomical regions. Clinical evidence shows that the prognosis of hypopharyngeal tumors is poorer than that of head and neck cancers in other anatomical locations. We investigated if tumor size or vascularity correlates with the biological behavior of these tumors. The results showed that the tumor size of laryngeal cancers in T2 stage were significantly larger than that of hypopharyngeal cancers in T4 stage. Regarding the vascularity or VEGF expression we did not find any difference between these two tumor types, suggesting that the more aggressive behavior of hypopharyngeal cancers is probably due to the invasive phenotype of this tumor, an assumption supported by genomic examination. In a prospective study we examined the relation between the microvascular density and treatment outcome in irradiated head and neck cancer patients. We demonstrated that the decreased vascularity induced by radiotherapy is a predictive marker of treatment success. We have investigated the role of the endocrine environment in tumor progression, determining the hormone receptor status of head and neck cancers using immunohistochemical and molecular methods. Results showed that ER and PGR are expressed in almost half of the examined tumors, and the presence of functional ER was also frequent in these cases (40.3%), while the solitary hormone receptor expression was a rare phenomenon. Expression of hormone receptors in all the examined cases did not show any correlation with patient survival but in the laryngeal/hypopharyngeal group ER positivity was associated with a shortened survival (p=0.0636). In a multicenter phase I/II clinical trial we examined the tumoral and stromal effects of a natural leukocyte interleukin (LI) in oral squamous cell cancers. LI was administered locally in four different doses. The proportion of tumor cell nests and tumor stroma decreased significantly after LI treatment (induction of fibrosis), which was associated with the induction of necrosis. Morphometric determination of Ki-67+ cells showed a tendency of cycling stromal cells to decrease in response to treatment by the different doses of LI, while lower doses of LI produced a temporary increase in cycling tumor cells. Density of intraepithelial neutrophils was higher after LI treatment, and the stromal density of neutrophils was higher in the responder subgroup. In the tumor stroma macrophage density was similar in the treated and control cases, while a significant decrease of these cells was observed intraepithelially. Finally, we were not able to detect CD34+ immunosuppressive mononuclear cells in these tumors. Our examinations supported the theory that the tumor stroma and its components play an important role in tumor progression, and therapeutic modulation of these components can influence the progression.
Lukits
Júlia
J
Semmelweis Egyetem Patológia Tudományok Doktori Iskola Budapest, Hungary. jlukits@t-online.hu