Canine mammary cancer tumour behaviour and patient survival time are associated with collagen fibre characteristics

Ana P V Garcia,Geovanni D Cassali,Fernanda C Nunes,Jeremy G Frey,Luana A Reis,Francis G J Longford,Ana M De Paula

doi:10.1038/s41598-021-85104-w

Ana P V Garcia, Geovanni D Cassali + Show 5 more

Open Access

https://doi.org/10.1038/s41598-021-85104-w

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Abstract

Precise diagnosis and prognosis are key in prevention and reduction of morbidity and mortality in all types of cancers. Here we show that changes in the collagen fibres in the main histological subtypes of canine mammary gland carcinomas are directly associated with the tumour behaviour and the animal survival time and could become a useful tool in helping with diagnosis. Imaging by second harmonic generation and multiphoton excited fluorescence microscopy were performed to evaluate the collagen and cellular segment parameters in cancer biopsies. We present a retrospective study of 45 cases of canine mammary cancer analysing 836 biopsies regions including normal mammary gland tissue, benign mixed tumours, carcinoma in mixed tumour, carcinosarcoma, micropapillary carcinoma and solid carcinoma. The image analyses and the comparison between the tumour types allowed to assess the collagen fibre changes during tumour progression. We demonstrate that the collagen parameters correlate with the clinical and pathological data, the results show that in neoplastic tissues, the collagen fibres are more aligned and shorter as compared to the normal tissues. There is a clear association of the mean fibre length with the dogs survival times, the carcinomas presenting shorter collagen fibres indicate a worse survival rate.

Highlights

Precise diagnosis and prognosis are key in prevention and reduction of morbidity and mortality in all types of cancers
The second harmonic generation (SHG) microscopy allows to obtain data regarding the morphology of the extracellular matrix, including the organization, shape and quantification of the collagen fibres that make up this matrix, characterizing the changes that occur in the fibres during tumour progression that facilitates the extravasation and migration of tumour cells in many types of cancers[14,16,18,22,23,31,37,42,43]
In relation to the clinical staging, 44% of the carcinomas were classified with staging IV (n = 20 ), 22% with staging I (n = 10 ), 18% with staging III (n = 8 ), 9% with staging V (n = 4 ) and 7% with staging II (n = 3 )

Summary

Introduction

Precise diagnosis and prognosis are key in prevention and reduction of morbidity and mortality in all types of cancers. In Brazil, this rate is even higher, reaching 29.7%, according to the National Cancer I nstitute[1] It is of great importance for public health that motivates studies on prevention and early diagnosis, in the search for the reduction of morbidity and mortality related to this neoplasm[2]. The SHG microscopy allows to obtain data regarding the morphology of the extracellular matrix, including the organization, shape and quantification of the collagen fibres that make up this matrix, characterizing the changes that occur in the fibres during tumour progression that facilitates the extravasation and migration of tumour cells in many types of cancers[14,16,18,22,23,31,37,42,43]. It has been shown that third harmonic generation microscopy allows to obtain details of the tumour cells with potential for differentiating malignant from benign breast tissue[45]

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