Canine mammary tumors (CMTs) are a dangerous condition in the modern era and are becoming more prevalent globally. Nevertheless, with the advent of advanced technology, it is possible to diagnose most of these tumors at an early stage (Pandey et al. 2018). Diagnosis of mammary tumors at an early stage is as important as in later stages, and they may metastasize. Diagnosis, if done via histopathology, involves invasive techniques of tissue collection. Milder steps like fine needle aspirate (FNA) are less invasive but less accurate also. As it is difficult to determine the biological behavior of mammary tumors by microscopic examination, markers are important tools in its diagnosis. With the advancement of research in cancer, various biomarkers have been successfully discovered for a different type of human neoplasia. Heat shock proteins are one of the potential biomarkers in human carcinogenesis (Kumar et al. 2018). HSP90α is a heat shock protein that also plays an indispensable role in immune responses and apoptosis.
Several reports advocate that HSP90α is upregulated in the different types of human cancer like breast cancer, liver, head, and neck cancer. Given the tight relationship between CMT and human breast cancer, we decided to investigate HSP90α expression in canine mammary cancers. Like our present study, many reports also observed that complex carcinoma, among all other canine mammary tumors, is the most persistent (Birdi et al. 2019; Kumar et al. 2018, Lopes-Neto et al. 2017; Mulligan 1975; Mitchell et al. 1974; Pandey et al. 2018).
Likewise, overexpression of the HSP90AA1 gene has been found in human breast cancer patients, related to poor prognosis and less survivability. (Klimczak et al. 2019). Yano M et al (1999) investigated the expression level of hsp90α, hsp90β, and cyclin D1 in human breast cancer. Breast cancer tissues were found to have significantly higher levels of mRNAs coding for hsp90α and cyclin D1 than non-cancer tissues. Previous studies have revealed over-expression of hsp90α also found in the different types of tumor-like in pancreatic carcinoma cells (Gress et al. 1994; Yano et al. 1999) and leukemic cells (Yano et al. 1999; Yufu et al. 1992). Detection of Hsp90α has been considered a poor prognostic marker of human breast cancer (Jameel et al. 1992; Yano et al. 1999). Also, one recent finding showed increased hsp90α in head and neck cancer (Fan et al. 2020). Our outcomes were consistent with these results, and we also reported overexpressed hsp90α in canine mammary tumors.
Different types of HSPs were also upregulated during the malignant alteration of mammary glands in pets. A recent study showed that Cytoplasmic Hsp90 protein level was significantly (p < 0.0001) higher in ductal carcinoma in situ and aggressive breast carcinomas than normal breast tissue. (Diehl et al. 2009). It has been reported that with a higher stage of mammary gland tissue malignancies, HSP90 expression has been correlated in dogs. The expression was highest in solid and complex carcinomas (Badowska-Kozakiewicz and Malicka 2012). Immunohistochemistry has also revealed that this isoform of HSP90 is overexpressed in distinct histotypes of canine mammary cancers. Grp94 was overexpressed in all forms of canine mammary cancers examined, regardless of histological types and grades (Kumar et al. 2018), which was similar to our present study in which Hsp90α, another isoform of heat shock protein, overexpressed in CMT histotypes. We are first to report an elevated level of Hsp90α expression in various histotypes of canine mammary tumors. Hence, adding Hsp90α to the current panel of CMT biomarkers will certainly improve the sensitivity and specificity of CMT diagnosis. However, owing to the lesser sample size, the data need to be confirmed in a study employing a large number and types of CMT in the future.