Abstract
One of the promising tools to evaluate collagen in the extracellular matrix is the second-harmonic generation microscopy (SHG). This approach may shed light on the biological behavior of cancers and their taxonomy, but has not yet been applied to characterize collagen fibers in cases diagnosed as invasive breast carcinoma (BC) of histological special types (IBC-ST). Tissue sections from 99 patients with IBC-ST and 21 of invasive breast carcinoma of no special type (IBC-NST) were submitted to evaluation of collagen parameters by SHG. Tissue microarray was performed to evaluate immunohistochemical-based molecular subtype. In intratumoral areas, fSHG and bSHG (forward-SHG and backward-SHG) collagen parameters achieved their lowest values in mucinous, papillary and medullary carcinomas, whereas the highest values were found in classic invasive lobular and tubular carcinomas. Unsupervised hierarchical cluster analysis and minimal spanning tree using intratumoral collagen parameters allowed the identification of three main groups of breast cancer: group A (classic invasive lobular and tubular carcinomas); group B (IBC-NST, metaplastic, invasive apocrine and micropapillary carcinomas); and group C (medullary, mucinous and papillary carcinomas). Our findings provide further characterization of the tumor microenvironment of IBC-ST. This understanding may add information to build more consistent tumor categorization and to refine prognostication.
Highlights
Invasive breast carcinoma is considered a combination of heterogeneous diseases, encompassing multiple entities with distinct biological and clinical features
IBC-ST refers to the architectural growth of the tumors, defining special morphological and cytological patterns, which have been consistently associated with distinctive clinical presentation and/or outcomes[3]
This is the case of tumor microenvironment, especially the extracellular matrix (ECM), which has been intensively studied in tumor progression and outcome[22]
Summary
Invasive breast carcinoma is considered a combination of heterogeneous diseases, encompassing multiple entities with distinct biological and clinical features. The use of new investigation tools in IBC-ST has been limited partly due to their relative low prevalence with consequent lower interobserver reproducibility, skewing their systematic investigation in class discovery[10,11,12,13] and class prediction[16,18,19,20,21] This is the case of tumor microenvironment, especially the extracellular matrix (ECM), which has been intensively studied in tumor progression and outcome[22]. One of the promising tools to evaluate collagen in the ECM during cancer progression is the second-harmonic generation microscopy (SHG)[25,26,27] This approach may shed light on the biological behavior of cancers and their taxonomy[28,29]. The goals of the present study are: (1) to investigate peri- and intratumoral collagen parameters in various histological subtypes of pure IBC-ST, using IBC-NST as standard samples, and (2) correlate these parameters with pathological and clinical features
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