Collagen fiber features and COL1A1: are they associated with elastic parameters in breast lesions, and can COL1A1 predict axillary lymph node metastasis?

Abstract

Background: This study aimed to explore whether collagen fiber features and collagen type I alpha 1 (COL1A1) are related to the stiffness of breast lesions and whether COL1A1 can predict axillary lymph node metastasis (LNM).

Methods: Ninety-four patients with breast lesions were consecutively enrolled in the study. Amongst the 94 lesions, 30 were benign, and 64 were malignant (25 were accompanied by axillary lymph node metastasis). Ultrasound (US) and shear wave elastography (SWE) were performed for each breast lesion before surgery. Sirius red and immunohistochemical staining were used to examine the shape and arrangement of collagen fibers and COL1A1 expression in the included tissue samples. We analyzed the correlation between the staining results and SWE parameters and investigated the effectiveness of COL1A1 expression levels in predicting axillary LNM.

Results: The optimal cut-off values for Emax, Emean, and Eratio for diagnosing the benign and malignant groups, were 58.70 kPa, 52.50 kPa, and 3.05, respectively. The optimal cutoff for predicting axillary LNM were 107.5 kPa, 85.15 kPa, and 3.90, respectively. Herein, the collagen fiber shape and arrangement features in breast lesions were classified into three categories. One-way analysis of variance (ANOVA) showed that Emax, Emean, and Eratio differed between categories 0, 1, and 2 (P < 0.05). Meanwhile, elasticity parameters were positively correlated with collagen categories and COL1A1 expression. The COL1A1 expression level > 0.145 was considered the cut-off value, and its efficacy in benign and malignant breast lesions was 0.808, with a sensitivity of 66% and a specificity of 90%. Furthermore, when the COL1A1 expression level > 0.150 was considered the cut-off, its efficacy in predicting axillary LNM was 0.796, with sensitivity and specificity of 96% and 59%, respectively.

Conclusions: The collagen fiber features and expression levels of COL1A1 positively correlated with the elastic parameters of breast lesions. The expression of COL1A1 may help diagnose benign and malignant breast lesions and predict axillary LNM.

Keywords: Breast lesions; COL1A1; Collagen; Lymph node metastasis; SWE.

Fig. 1

Flowchart of patient enrollment

Fig. 2

The comparison of SWE (A, D, G), COL1A1 immunohistochemical staining (B, E, H: × 200), and collagen Sirius staining (C, F, I: × 400) of breast lesions between the benign (A, B, C), LNM—(D, E, F) and LNM + (G, H, I) groups. SWE, shear wave elastography; COL1A1, collagen type I alpha 1; LNM, lymph node metastasis

Fig. 3

The ROC curve of in the differential diagnosis of three groups. A The ROC curve of elastic parameters and the COL1A1 expression level in the differential diagnosis of benign and LNM- groups. B The ROC curve of elastic parameters and the COL1A1 expression level in the differential diagnosis of LNM- and LNM + groups. ROC, receiver operating characteristic; COL1A1, collagen type I alpha 1; Emax, maximum elasticity; Emean, mean elasticity; Eratio, elasticity ratio of the lesions to peripheral tissue; LNM, lymph node metastasis

Fig. 4

Pairwise comparison of elasticity parameters and COL1A1 expression levels in three groups. ****, P < 0.0001; ***, P < 0.001; **, P < 0.05; LNM, lymph node metastasis; COL1A1, collagen type I alpha 1; Emax, maximum elasticity; Emean, mean elasticity; Eratio, the elasticity ratio of the lesions to the peripheral tissue

Fig. 5

The expression level of COL1A1 was positively correlated with Emax(A), Emean(B), Eratio(C), (r = 0.406, 0.362, 0.425, respectively. P < 0.001). COL1A1, Collagen type I alpha 1; Emax, maximum elasticity; Emean, mean elasticity; Eratio, the elasticity ratio of the lesions to the peripheral tissue