Expression of Myoepithelial Markers in Mammary Carcinomas of 119 Pet Rabbits

Abstract

Simple SummaryMammary cancer is a serious health issue in pet rabbits; prognostic factors are unknown. In a normal mammary gland, glandular secretory cells are surrounded by a single continuous layer of myoepithelial cells. In non-invasive mammary carcinomas, tumor cells are delineated by an intact myoepithelial layer, which is gradually lost to invasive carcinomas. The main aim of this study was to determine in rabbit mammary carcinomas (n = 119) the expression of myoepithelial markers that have prognostic significance in human cancer. Results show that all cases contained some retained myoepithelial cells. In 93% of the tumors, neoplastic cells expressed the myoepithelial marker calponin. There was a statistically significant association between higher percentages of calponin-containing cancer cells and histological features indicative of a better tumor differentiation, i.e., a lower proliferation of tumor cells, an increased percentage of tubular growth within the tumor, and a lower tumor grade, respectively. These results suggest that rabbit mammary carcinomas develop from progression of non-invasive cancer forms, and that calponin expression in cancer cells likely represents a favorable prognostic factor. The latter hypothesis has to be confirmed in long-term follow-up studies.AbstractMost mammary tumors in pet rabbits are carcinomas; prognostic factors are unknown. The aim of this study on rabbit mammary carcinomas was to determine the expression of myoepithelial markers that have a prognostic relevance in human cancers. Mammary carcinomas (n = 119) of female or female-spayed pet rabbits were immunostained for cytokeratin AE1/AE3, vimentin, smooth muscle actin (SMA), and calponin; and percentages of non-neoplastic myoepithelial cells (ME cells) and calponin-positive neoplastic cells were determined. Using statistical analysis, data were correlated with the age of the rabbits and histological tumor characteristics. All carcinomas contained retained spindle-shaped ME, while 115 also contained hypertrophic ME (HME). A statistically significant relationship existed between a higher age and an increase in HME. In 111 carcinomas (93%), tumor cells expressed calponin. There was a significant correlation between higher percentages of calponin-positive tumor cells and a lower mitotic count, an increased percentage of tubular growth, and a lower grading score, respectively. Data suggest that pet rabbit mammary carcinomas develop from progression of in situ cancer and that the extent of calponin expression in tumor cells influences their biological behavior. These results provide the basis for a long-term follow-up on the prognostic significance of calponin expression in mammary cancer cells.

Tumor Infiltrating Lymphocytes in Pet Rabbit Mammary Carcinomas: A Study with Relevance to Comparative Pathology

“…These tissue samples were also used for the microscopic evaluation of TILs. In addition, histological features associated with the degree of tumor differentiation (reported below), the ERα and PR status as well was the percentages of calponin positive tumor cells were extracted from the databases and diagnostic records [10,11].…”

“…Histological parameters extracted from the databases were the tumor area with a tubular growth pattern in percent of the entire tumor area, the mitotic count per ten 40× high power fields (HPFs) under consideration of the field number of the microscope, the degree of nuclear pleomorphism, as well as the degree of tumor invasion [10,11,15]. The results of the former three parameters were used to determine the histological tumor grade [32][33][34].…”

“…The results of the former three parameters were used to determine the histological tumor grade [32][33][34]. Depending on the degree of tissue infiltration, tumors were classified as those with mild, moderate, or marked invasive behavior [10,11,15]. Necrosis was recorded as minimal, mild, moderate, and marked, if it affected <10%, 10-39%, 40-69%, and ≥70% of the tumor area, respectively [10].…”

“…The suitability of rabbits as animal models for human diseases is facilitated by the availability of comprehensive data on their innate and adaptive immune mechanisms [1,8,9], close similarities between the rabbit and human immune systems [1,4], and very similar expression and functions of key genes between humans and rabbits [2]. Recent investigations on spontaneous mammary carcinomas of pet rabbits, identified the pet rabbit as potential animal model for certain types of spontaneous human mammary tumors [10][11][12]. This eligibility is further supported by the following aspects: In contrast to rodents, mammary glands of does and women contain independent ductal systems with separate teat orifices [13].…”

“…It has been shown that most rabbit mammary tumors are carcinomas, i.e., 50-98% depending on the respective study, the majority of these being adenocarcinomas [10][11][12]15,16]. Recent investigations on rabbit mammary carcinomas analyzed in detail the histological features [10,15,16], estrogen and progesterone receptor status [10], as well as the intra-tumoral presence of retained non-neoplastic myoepithelial cells and tumor cells with a myoepithelial differentiation [11,15]. Definitive prognostic factors are not available yet, and currently the only therapeutic option is surgical excision [12].…”