HER-2 and EGFR mRNA Expression and Its Relationship with Versican in Malignant Matrix-Producing Tumors of the Canine Mammary Gland

Abstract

Versican expression promotes tumor growth by destabilizing focal cell contacts, thus impeding cell adhesion and facilitating cell migration. It not only presents or recruits molecules to the cell surface, but also modulates gene expression levels and coordinates complex signal pathways. Previously, we suggested that the interaction between versican and human epidermal growth factor receptors may be directly associated with tumor aggressiveness. Thus, the expression of EGFR and HER-2 in these neoplasms may contribute to a better understanding of the progression mechanisms in malignant mammary tumors. The purpose of this study was to correlate the gene and protein expressions of EGFR and HER2 by RNA In Situ Hybridization (ISH) and immunohistochemistry (IHC), respectively, and their relationship with the versican expression in carcinomas in mixed tumors and carcinosarcomas of the canine mammary gland. The results revealed that EGFR mRNA expression showed a significant difference between in situ and invasive carcinomatous areas in low and high versican expression groups. Identical results were observed in HER-2 mRNA expression. In immunohistochemistry analysis, neoplasms with low versican expression showed greater EGFR immunostaining in the in situ areas than in invasive areas, even as the group presenting high versican expression displayed greater EGFR and HER-2 staining in in situ areas. Significant EGFR and HER-2 mRNA and protein expressions in in situ carcinomatous sites relative to invasive areas suggest that these molecules play a role during the early stages of tumor progression.

Mixed tumors of the canine mammary glands: Evaluation of prognostic factors, treatment, and overall survival

“…Tumor size is an independent and well-established prognostic factor in canine mammary neoplasms ( Bostock, 1986 , Misdorp and Hart, 1976 , Gilbertson et al., 1983 , Yamagami et al., 1996 ). In our study, smaller lesions (T 1 and T 2 ) occurred mainly in benign mixed tumors and carcinomas in mixed tumors, and more T 3 lesions were observed among carcinosarcomas, corroborating the results of Damasceno et al. (2016) .…”

Three-dimensional culture system identifies a new mode of cetuximab resistance and disease-relevant genes in colorectal cancer

“…VCAN was the most up-regulated gene in SC. Of interest, VCAN has also been shown to interact with and influence EGFR signaling (50,51). VCAN is a major component of the extracellular matrix, being produced by both tumor cells and the surrounding stroma (52).…”

The investigation of transcriptional repression mediated by ZEB2 in canine invasive micropapillary carcinoma in mammary gland

“…RNA In Situ Hybridization method (ISH) was performed as previously described with minor modifications [36,37]. The RNAscope (Advanced Cell Diagnostics, Inc., Hayward, California) approach was used in archival formalin-fixed, paraffin-embedded (FFPE) tissue to view ZEB2 and E-cadherin mRNA in individual cells through a probe design strategy and hybridization-based on a signal amplification system to amplify signals and suppress background (ZEB2: the reference sequence, XM_005631964.1; probe region, 1362–2409; CDH1 : the reference sequence, NM_001287125.1; probe region, 1347–2279).…”