The Combined Expression Pattern of BMP2, LTBP4, and DERL1 Discriminates Malignant From Benign Canine Mammary Tumors

Abstract

Several markers of malignancy have been proposed for canine mammary tumors on the mRNA and protein levels. However, their association with tumor malignancy applies only for mean values of large groups of tumors, but no single marker identified to date can be used to reliably predict malignancy for individual tumors. A quantitative real-time reverse transcription polymerase chain reaction array was established to quantify the expression levels of 49 genes relevant to carcinogenesis in laser-microdissected tumor cells of 10 benign and 13 metastatic canine mammary tumors. Analysis of variance and discriminant analysis were used to identify relevant gene expression patterns that differentiate adenomas from metastatic carcinomas and their lymph node metastases. Seventeen genes with significant (P < .05) differences in gene expression levels between benign and malignant tumors were identified--including ERBB1, SLIT2, progesterone receptor, MIG6, SATB1, and SMAD6--but correct classification of each tumor as benign or malignant was impossible on the basis of any of these genes alone. However, the combined expression patterns of BMP2, LTBP4, and DERL1 (Derlin-1) correctly classified each individual tumor as benign or malignant. This pilot study identified a complex mRNA expression pattern of 3 genes that was able to identify malignancy in laser-microdissected tumor cells for each individual tumor, instead of group means as used in previous studies.

Different variants of equine hemangiosarcomas

“…3, 4 and 5) with an additional infiltration of the adjacent ventral cervical muscles. Maceration and HE stain, according to standard protocols (Klopfleisch et al, 2010), confirmed the diagnosis of a hemangiosarcoma without metastatic spread to other organs.…”

Pathological Classification of Canine Mammary Tumor Based on Quantifying mRNA Levels of Hormonal Receptors, SATB1, and Snail in Tissue and Fine Needle Biopsy Samples

“…Ahern et al reported overexpression of HER2 mRNA in 17 of 23 malignant CMTs, but in none of 5 benign CMTs [1]. A recent study reported no differences in the HER2 mRNA levels between adenomas and carcinomas or between presence and absence of lymph node involvement of cMTs [23]. In human breast cancer, reports on the interaction between mRNA expression and HER2 protein or DNA amplification levels did not reach agreement [5,13].…”

“…To identify gene biomarkers in cMTs, quantification of the mRNA levels of many genes, includ-ing hormonal receptors and HER2, have been reported [21,23,31,34]. In these studies, mRNA was extracted from mammary tumor tissue samples, but few reports assessed the gene expressions of biomarkers in FNB samples.…”

Malignancy Associated MicroRNA Expression Changes in Canine Mammary Cancer of Different Malignancies

“…The lymph node metastases were microdissected from cryostat sections by laser capture microdissection as previously described [11]. All miRNA and snoRNA species were elongated prior to cDNA synthesis by universal poly-A-tailing and amplified by quantitative reverse transcription PCR as previously described [9].…”