Envolvimento de vias hormonais em lesões tumorais de cabeça e pescoço: uma comparação entre animais machos e fêmeas transgênicos para HPV16

Abstract

Background: Head and neck cancer (HNC) is the fifth most common cancer in the world. Human papillomavirus (HPV) is an important risk factor for this neoplasm. Hormonal receptors have been implicated in the pathogenesis of several tumors. Animal studies are useful for reproducing biological processes in controlled environments. The aim of this study was to determine the status of alpha and beta estrogen and metalloproteinase-2 (MMP-2) receptors in the CCP in HPV16 transgenic mice. Methods: 289 head and neck samples from 149 K14-HPV16 transgenic mice (67 males and 82 females) and 20 wild mice (10 males and 10 females) were studied. The animals were packaged at the University de Trás-os-Montes e Alto Douro (UTAD) and the samples sent to the Tumor and DNA Bank of Maranhão (BTMA) for histological analysis with Hematoxylin and Eosin and Picrosirius staining, and immunohistochemistry for receptor of alpha estrogen (ERα), estrogen beta receptor (ERβ), progesterone receptor (PR) and MMP-2. The expression of ERα, ERβ, PR and MMP-2 was quantified using the product between the percentage of marked cells and the intensity of the marking (H score). The data were analyzed using the GraphPad Prism program to identify statistical differences between males and females. Results: Malignant lesions were present in 23.1% of females and 4.5% of males (p = 0.0071). As for the location of the lesions, they were located almost exclusively on the tongue, especially at the base of the tongue, but only a statistically significant difference was found in the females (p = 0.0003). The collagen distribution was considered increased in 77.8% of the female samples and normal in all the male samples (p = 0.0307). There was no expression of RP in the studied samples. Male tumors had no expression for estrogen receptors. In females there was 71% positivity for ERα, 43% positivity for ERβ and 66% positivity for MMP-2. The H score was statistically significant in intraepithelial lesions for MMP-2 (p = 0.0151), in the stroma of intraepithelial lesions for ERα and ERβ (p = 0.0005) and in the tumor stroma for ERα (p = 0.0278). Conclusion: The presence of ERα in the stroma of pre-malignants and malignant lesions of the head and neck was verified in transgenic females. There was no statistical significance in the expression of estrogen receptors in tumors. There was a moderate correlation between the expression of ERα and MMP-2 in intraepithelial and tumor lesions of the head and neck. These findings suggest that the receptor's action may occur in the microenvironment in which the tumor is located. The expression of hormone receptors can have prognostic and therapeutic value, however more studies are needed.