An Immunohistochemical Study of HER-2 Expression in Feline Mammary Tumours

Rasotto, Roberta; Caliari, D.; Castagnaro, Massimo; Zanetti, Rossella; Zappulli, Valentina

doi:10.1016/j.jcpa.2010.08.010

Cited by 48 publications

(98 citation statements)

References 37 publications

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“…37 Recently, some studies assessed Ki-67 expression in feline mammary tumors and showed that malignant lesions exhibited higher Ki-67 levels that benign lesions. 3,4,23,32,33,37 In the present study, we demonstrated that the Ki-67 labeling index in the primary tumor reveals a strong and positive correlation with the Ki-67 index of local and distant metastasis. Moreover, and besides the small sample (n ¼ 16), the metastatic lesions had significantly higher Ki-67 indices than the primary lesions (means of 48.2% vs 26%), corroborating the association between Ki-67 overexpression in the primary tumor and aggressive tumor behavior.…”

Section: Discussionsupporting

confidence: 63%

Ki-67 as a Prognostic Factor in Feline Mammary Carcinoma

et al. 2015

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Ki-67 is a nuclear protein and a proliferation marker frequently used in establishing the prognosis for breast cancer patients. To investigate the prognostic value of the Ki-67 proliferation index in female cats with mammary carcinoma, a prospective study was conducted with 96 animals. The Ki-67 index of primary tumors (n ¼ 96) was initially determined, and whenever possible, the Ki-67 index of regional lymph node metastasis (n ¼ 38) and distant metastasis (n ¼ 16) was also estimated. The optimal cutoff value for the Ki-67 index was determined by univariate and multivariate analysis. Ki-67 indices 14% were detected in 72.9% (70 of 96) of the tumors. Tumors with a Ki-67 index 14% were significantly associated with large size (P ¼ .022), poor differentiation (P ¼ .009), presence of necrotic areas (P ¼ .008), estrogen receptor-negative status (P < .0001), fHER2-negative status (P ¼ .003), and shorter overall survival (P ¼ .012). Moreover, Ki-67 expression in the primary tumor was strongly and positively correlated with both regional metastasis (P < .0001; r ¼ 0.83) and distant metastasis (P < .0001; r ¼ 0.83), and was significantly higher in distant metastases when compared with the primary tumor (P ¼ .0009). A similar correlation was also observed between regional and distant metastasis (P < .0001; r ¼ 0.75). On the basis of the above results, the authors propose the adoption of the 14% value as the optimal cutoff for Ki-67 to identify tumors with high risk of disease progression.Keywords feline mammary carcinoma, Ki-67 proliferation index, prognostic factor, cutoff value Feline mammary carcinomas (FMCs) are among the most prevalent tumors in cats, with an incidence that can reach 40% of all tumor cases in this species. 23,39,42 Contrary to those of humans and dogs, 85% to 93% of feline mammary tumors are considered malignant, and the most common histotypes are the tubular, papillary, solid, and cribriform carcinomas. 39 Feline mammary tumors may metastasize to the regional lymph nodes, lungs, and liver, as well as other organs. Although some studies correlate age, tumor size, presence of regional metastasis, and malignancy grade with overall survival (OS), 19,37,43 still scarce information is available regarding the proliferation index of FMC. Based on this scenario, additional prognostic and predictive factors may provide useful insights into tumor biology to achieve a more efficient therapy and a better follow-up of the affected female cats.Ki-67 is a protein found only in growing, dividing cells. It is expressed in all cell cycle phases, except in the resting phase (G0). With an intranuclear localization, the expression levels of Ki-67 are low during the G1 and S phases, rapidly increase during the G2 phase, and reach a peak in mitosis. This well-defined expression pattern makes the Ki-67 antigen a good proliferation marker, very useful and reliable in the prognosis of human breast cancer. 9,45 Several studies of women demonstrated that high Ki-67 expression is a poor prognostic indicator of 5-year rec...

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Section: Discussionsupporting

confidence: 63%

Ki-67 as a Prognostic Factor in Feline Mammary Carcinoma

et al. 2015

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“…This cytoplasmic immunoreactivity was considered as an immunohistochemical artifact both in human and feline cancer tissues due to lack of IHC protocol standardization [37,38]. However, in the present study, the cytoplasmic signal was consistently observed upon IHC protocol optimization.…”

Section: Discussionmentioning

confidence: 51%

Investigation of HER2 expression in canine mammary tumors by antibody-based, transcriptomic and mass spectrometry analysis: is the dog a suitable animal model for human breast cancer?

Burrai

Tanca²,

Miglio

et al. 2015

Tumor Biol.

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Canine mammary tumors (CMTs) share many features with human breast cancer (HBC), specifically concerning cancer-related pathways. Although the human epidermal growth factor receptor 2 (HER2) plays a significant role as a therapeutic and prognostic biomarker in HBC, its relevance in the pathogenesis and prognosis of CMT is still controversial. The aim of this study was to investigate HER2 expression in canine mammary hyperplasic and neoplastic tissues as well as to evaluate the specificity of the most commonly used polyclonal anti HER2 antibody by multiple molecular approaches. HER2 protein and RNA expression were determined by immunohistochemistry (IHC) and by quantitative real-time (qRT) PCR. A strong cell membrane associated with non-specific cytoplasmic staining was observed in 22% of carcinomas by IHC. Adenomas and carcinomas exhibited a significantly higher HER2 mRNA expression when compared to normal mammary glands, although no significant difference between benign and malignant tumors was noticed by qRT-PCR. The IHC results suggest a lack of specificity of the FDA-approved antibody in CMT samples as further demonstrated by Western immunoblotting (WB) and reverse phase protein arrays (RPPA). Furthemore, HER2 was not detected by mass spectrometry (MS) in a protein-expressing carcinoma at the IHC investigation. This study highlights that caution needs to be used when trying to translate from human to veterinary medicine information concerning cancer-related biomarkers and pathways. Further investigations are necessary to carefully assess the diagnostic and biological role specifically exerted by HER2 in CMTs and the use of canine mammary tumors as a model of HER2 over-expressing breast cancer.

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“…Data concerning HER2 status in FMTs are highly controversial with values ranging from 5.5% to 90% of positive tumors probably due to different protocols and evaluation methods [17,19,20,22,23,38,40]. In our work we evaluated HER2 by RT-PCR and we found no significant difference in HER-2 expression between FMCs and matched non-neoplastic tissues.…”

Section: Discussionmentioning

confidence: 58%

“…For IHC analysis paraffin-embedded samples, submitted to the Diagnostic Service of Veterinary Anatomical Pathology (University of Padua, Italy) routinely collected during surgery and processed as previously described [22], were used. Distant metastases were not reported at the time of diagnosis.…”

Section: Methodsmentioning

confidence: 99%

Triple-negative vimentin-positive heterogeneous feline mammary carcinomas as a potential comparative model for breast cancer

et al. 2014

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BackgroundHuman breast cancer is a heterogeneous disease classified by molecular subtyping into luminal A, luminal B, HER2-overexpressing, basal-like, claudin-low and normal-breast like. The routinely applied and standardized immunohistochemical-based surrogates of this classification group together the last three entities as triple-negative breast cancer (TNBCs) that show the most diverse and complex heterogeneity and represent a therapeutic challenge.In the present work 156 feline mammary lesions consisting of feline mammary carcinomas (FMCs), benign neoplasms, and hyperplastic/dysplastic tissues were evaluated histologically and by immunohistochemistry for expression of basal and luminal cytokeratins (CK), vimentin, alpha-smooth muscle actin, calponin, estrogen receptor (ER) alpha (a), and progesterone receptor (PR). Thirty-seven FMCs with 27 matched non-neoplastic controls were also investigated for gene expression of ERa, ER beta, PR, and HER2.ResultsA large group of hormone receptors (HRs)-negative aggressive carcinomas - that did not overexpress HER2 - could be distinguished from the less aggressive (10.8%) and benign (8%) HRs + tumors, that showed bilineage (luminal and myoepithelial) differentiation. Immunohistochemical evaluations of cytoplasmic filaments indicated that HRs- FMCs are vimentin+, CK14+, and CK5_6+ carcinomas that may resemble the TNBCs (basal like/claudin low) described in women. The identification of luminal and myoepithelial progenitors within the mammary ductal system suggested potential cells/sites of origin of these tumors. A diffuse and never previously described CKs/vimentin luminal cell co-expression was detected in the non-neoplastic ducts, indicating a potential bilineage progenitor.ConclusionsThese results indicate and potentially explain the high incidence of triple-negative, vimentin + aggressive tumors in cats that may used to elucidate some of the challenging features of TNBCs in women.

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An Immunohistochemical Study of HER-2 Expression in Feline Mammary Tumours

Cited by 48 publications

References 37 publications

Ki-67 as a Prognostic Factor in Feline Mammary Carcinoma

Ki-67 as a Prognostic Factor in Feline Mammary Carcinoma

Investigation of HER2 expression in canine mammary tumors by antibody-based, transcriptomic and mass spectrometry analysis: is the dog a suitable animal model for human breast cancer?

Triple-negative vimentin-positive heterogeneous feline mammary carcinomas as a potential comparative model for breast cancer

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