scholarly journals Immunohistochemical study of IGF-I and IGF-II expression in canine mammary tumours: Prognostic and diagnostic role

Author(s):  
Ozlem Ozmen

AbstractMammary tumours are among the most common tumours in dogs and are of interest due to their similarities to human breast tumours. Insulin-like growth factors (IGFs) are considered important in cell growth and development. The aim of this study was to investigate the immunohistochemical expression of IGF-I and IGF-II in benign and malignant canine mammary tumours. In this study, 10 benign and 10 malignant mammary tumours from the archives of the Department of Pathology were used, and five normal breast tissues were used as controls. It was observed that the expression of IGF-I and IGF-II was low to absent in benign tumours and increased in malignant tumours. The expression of IGF-II was higher than that of IGF-I. This study showed that IGF-I and IGF-II can be used as criteria for malignancy in canine mammary tumours. The results also indicate that IGF-I and IGF-II may be used as early diagnostic markers, and their inhibition may be used for the treatment of canine and human mammary tumours in the future.

2019 ◽  
Author(s):  
Parisa Amini ◽  
Sina Nassiri ◽  
Alexandra Malbon ◽  
Enni Markkanen

AbstractThe importance of cancer-associated stroma (CAS) for initiation and progression of cancer is well accepted. However, as stromal changes in benign forms of naturally occurring tumours are poorly understood, it remains unclear how CAS from benign and malignant tumours compare. Spontaneous canine mammary tumours are viewed as excellent models of human mammary carcinomas (mCA). We have recently reported highly conserved stromal reprogramming between canine and human mCA based on transcriptome analysis of laser-capture-microdissected FFPE specimen. To identify stromal changes between benign and malignant mammary tumours, we have analysed CAS and matched normal stroma from 13 canine mammary adenomas and compared them to 15 canine mCA. Our analyses revealed distinct stromal reprogramming even in small benign tumours. While similarities in stromal reprogramming exist, the CAS signature clearly distinguished adenomas from mCA, suggesting that it may reliably discriminate between benign and malignant tumours. We identified strongly discriminatory genes and found strong differential enrichment in several hallmark signalling pathways between benign and malignant CAS. The distinction between CAS from adenoma and mCA was further substantiated by differential abundance in cellular composition. Finally, to determine key players in CAS reprograming between adenomas and mCA, a network-based gene screening method identified modules of co-expressing genes with distinct expression profile in benign and malignant CAS, and revealed several hub genes as potential molecular drivers in CAS. Given the relevance of canine CAS as a model for the human disease, our approach identifies potential stromal drivers of tumour malignancy with implications for human mCA.Summary statementRNAsequencing-based analysis of stromal reprogramming between benign and malignant naturally occurring canine mammary tumours identifies potential molecular drivers in cancer-associated stroma that support tumour growth and malignancy.


Author(s):  
J. H. H. Thijssen ◽  
M. A. Blankenstein

SynopsisThe levels of endogenous steroids in the target tissues are thought to be more closely related to the biological effects than their concentrations in plasma. Therefore studies on oestrogen levels in malignant and non-malignant breast tissues (expressed per g wet weight) were conducted and the following conclusions were drawn:(1) malignant tumours contained higher oestradiol levels than normal or benign breast tissues, whereas oestrone levels were more comparable;(2) in contrast to the large decrease in plasma concentrations after menopause, the levels of oestradiol in tumours and in normal breast tissue did not change with advancing age;(3) the oestradiol levels in breast tissues were lower than in uterine tissues, particularly in women before menopause; oestrone levels were very similar in all tissues studied;(4) the mean oestradiol level was higher in oestrogen-receptor-positive tumours, but no correlation between the two parameters was found;(5) preliminary results indicated lower oestradiol levels in tumours obtained from countries with a lower incidence of breast cancer;(6) as far as available, oestrone levels were comparable and those of oestradiol were lower in fat tissues than in breast tumours;(7) neither in vitro studies with breast tumours, nor in vivo results using myometrial tissues support a prominent role of the metabolism of oestrogens at the 16α-position in the development of tumours;(8) the role of local factors in the production, retention and metabolism of oestradiol in the breast remains to be elucidated.


2014 ◽  
Vol 62 (2) ◽  
pp. 194-204 ◽  
Author(s):  
Zsófia Koltai ◽  
Péter Vajdovich

The aim of this study was to determine the expression rate of P-glycoprotein (Pgp), a multidrug resistance marker and the p53 tumour-suppressor protein in canine mammary tumours. A total of 30 tumours were examined in parallel to patient history. The tumours were allotted to four groups: tubulopapillar carcinomas, complex carcinomas, benign tumours, and other malignant tumours. A monoclonal mouse antibody (C494) was used for the immunohistochemical evaluation of Pgp and a polyclonal rabbit antibody for p53. We found that the intact ductal epithelium and connective tissue showed pronounced Pgp expression. The most intensive staining was detected in tubulopapillar carcinomas for both Pgp and p53. The expression rate of Pgp and p53 differed significantly between tubulopapillar carcinoma and complex carcinoma, and between tubulopapillar carcinoma and benign mammary tumour, respectively. The expressions of Pgp and p53 highly correlated statistically; therefore, both can determine malignancy in a similar manner. In the case of tubulopapillar carcinomas, more relapsed tumours occurred than in relation to complex carcinomas and other malignant tumours. Pgp expression rate was proportional to the probability of the tumour becoming recidivant postoperatively, as well. These results suggest that routine evaluation of Pgp expression in canine mammary tumours may be prognostically helpful.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Siru Virtanen ◽  
Reiner Schulte ◽  
John Stingl ◽  
Carlos Caldas ◽  
Mona Shehata

Abstract Background Normal human breast tissues are a heterogeneous mix of epithelial and stromal subtypes in different cell states. Delineating the spectrum of cellular heterogeneity will provide new insights into normal cellular properties within the breast tissue that might become dysregulated in the initial stages of cancer. Investigation of surface marker expression provides a valuable approach to resolve complex cell populations. However, the majority of cell surface maker expression of primary breast cells have not been investigated. Methods To determine the differences in expression of a range of uninvestigated cell surface markers between the normal breast cell subpopulations, primary human breast cells were analysed using high-throughput flow cytometry for the expression of 242 cell surface proteins in conjunction with EpCAM/CD49f staining. Results We identified 35 surface marker proteins expressed on normal breast epithelial and/or stromal subpopulations that were previously unreported. We also show multiple markers were equally expressed in all cell populations (e.g. CD9, CD59, CD164) while other surface markers were confirmed to be enriched in different cell lineages: CD24, CD227 and CD340 in the luminal compartment, CD10 and CD90 in the basal population, and CD34 and CD140b on stromal cells. Conclusions Our dataset of CD marker expression in the normal breast provides better definition for breast cellular heterogeneity.


Author(s):  
Sarah Carpenter ◽  
Gregory Georgiade ◽  
Kenneth S. McCarty ◽  
Kenneth S. McCarty

SynopsisThe human breast undergoes profound changes during the menstrual cycle. The development of monocloiial antibodies to oestrogen-receptors (ER) allows study of receptor content and distribution in individual components of breast tissue. Forty-one specimens from premenopausal patients who underwent bilateral mastectomy for benign conditions were evaluated. The patients were categorised into early follicular, late follicular, early luteal, late luteal, and menstrual phases. An HSCORE, a semiquantitative evaluation of the intensity and distribution of receptor antigen localisation, was evaluated for the ductal and lobular epithelia as a tissue mean HSCORE. ER localised to the nuclei of the epithelium and was not observed in stromal elements. Receptor concentration was greater for ER in the follicular phase but this finding was not as striking as differences between lobules in a single breast and even between breasts. This heterogeneous expression between lobules was in contrast to the relatively uniform expression of receptor within a lobule of a given specimen.


2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A10.2-A11
Author(s):  
O Braubach ◽  
S Basak ◽  
M Gallina ◽  
W Lee ◽  
J Kim ◽  
...  

BackgroundBreast cancer has a high incidence rate and there is a need to develop new diagnostic tools and treatment regimens. Progress has, unfortunately, been slow and new technologies are urgently needed to generate a comprehensive understanding of breast cancer biology. Highly multiplexed imaging is an emerging tool that can help to unravel the complexities of the tumor microenvironment. This technology enables the detection of tens of biomarkers within a tissue specimen, and allows comprehensive cell phenotyping, biomarker quantification and spatial localization at cellular resolution. Such measurements can, in turn, provide insights into disease mechanisms and identify potential treatment targets. We demonstrate the development of a breast cancer specific CO-Detection by indEXing (CODEX®) panel that allows simultaneous in situ imaging of more than 30+ antibody markers.Materials and MethodsCODEX® relies on a DNA-based tagging approach, whereby antibodies are labeled with specific oligonucleotide tags (barcodes) and dye-oligonucleotides (reporters) are iteratively hybridized and dehybridized across multiple cycles. This process is completely automated through the CODEX® instrument and readily deployable on commercially available fluorescence microscopy systems. Using a 30+ antibody CODEX® panel, we compared formalin-fixed paraffin embedded (FFPE) human breast cancer tissues at different stages of disease progression with normal breast tissues. Our antibody panel was designed to detect cancer cells as well as non-malignant cells in order to comprehensively survey the tumor microenvironment and normal control tissues. Data were analyzed using the CODEX® software suite to identify key cell types and analyze spatial associations.ResultsOur analyses revealed more than 20 distinct cell types in human breast cancer and normal tissues. Cell populations, biomarker expression and cellular spatial distributions differed distinctly between cancerous and normal breast tissues. Differences were robust, repeatedly observed and indicative of altered cellular milieus in normal versus cancerous breast tissues.ConclusionsCollectively, these data establish CODEX® as a readily deployable and practical tool for spatially-resolved, highly multiplexed biomarker analysis of human FFPE samples.Disclosure InformationO. Braubach: A. Employment (full or part-time); Significant; Akoya Biosciences. S. Basak: A. Employment (full or part-time); Significant; Akoya Biosciences. M. Gallina: A. Employment (full or part-time); Significant; Akoya Biosciences. W. Lee: A. Employment (full or part-time); Significant; Akoya Biosciences. J. Kim: A. Employment (full or part-time); Significant; Akoya Biosciences. C. Hempel: A. Employment (full or part-time); Significant; Akoya Biosciences. E. Williams: A. Employment (full or part-time); Significant; Akoya Biosciences. O. Shang: A. Employment (full or part-time); Significant; Akoya Biosciences. B. Cheung: A. Employment (full or part-time); Significant; Akoya Biosciences. J. Kennedy-Darling: A. Employment (full or part-time); Significant; Akoya Biosciences.


2010 ◽  
Vol 79 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Jana Lorenzová ◽  
Michal Crha ◽  
Helga Kecová ◽  
Lucie Urbanová ◽  
Renata Stavinohová ◽  
...  

This retrospective study evaluated a canine patient group operated on for mammary neoplasms (221 females). After surgical treatment, the animals were divided based on histological findings into groups and subgroups according to the WHO system. In the individual groups and subgroups the length of their survival following a mammary tumour surgery and death causes were followed. Of their total number, 164 tumours were malignant, 39 were benign and 18 were mammary hyperplasias. With regard to malignant tumours, invasive tubular carcinoma (20.81%) was identified most frequently; fibroadenoma reached the highest occurrence (10.41%) as regards benign tumours. The length of survival in females with malignant tumours ranged from 12 to 37.4 months, depending on histological subtypes. In females with benign mammary neoplasms the length of survival ranged from 39.1 to 59.3 months and in animals with hyperplasia it was 50.2 months. As a result of mammary tumour, 41 females (25%) died in the malignant tumour group, none died in the benign tumour group and 2 females (11.1%) died in the hyperplasia group. The survival periods in surgically treated patients with mammary tumours were shorter for solid and complex carcinomas, compared to patients affected with the remainder of the histological subtypes. The longest survival period following operation was recorded in the group suffering from adenoma. The least favourable illness prognosis for patients with mammary tumours in respect to linking the death cause to the mammary tumour was for those having invasive papillary carcinoma. The most favourable illness prognosis was for patients with benign tumours and non-invasive tubular carcinoma. A frequent death cause in females with mammary tumours was another illness unrelated to mammary tumours.


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