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. 2019 Mar 15:12:2023-2033.
doi: 10.2147/OTT.S187835. eCollection 2019.

Microcalcification and BMP-2 in breast cancer: correlation with clinicopathological features and outcomes

Li Zhang  1 , Chunfang Hao  1 , Yansheng Wu  2 , Yuying Zhu  1 , Yulin Ren  1 , Zhongsheng Tong  1
Affiliations

Microcalcification and BMP-2 in breast cancer: correlation with clinicopathological features and outcomes

Li Zhang et al. Onco Targets Ther. .

Abstract

Background: Microcalcification is a very important diagnostic information in breast cancer. The purpose of this study was to determine the relationship of clinicopathological features and prognosis of breast cancer with microcalcification and to detect biomarkers related to the possible mechanisms of microcalcifications.

Patients and methods: All 529 subjects with microcalcifications were selected from patients who had been examined using breast mammography. The control group did not have detectable microcalcifications, and was matched in a ratio of 1:3. The clinicopathological factors, progression-free survival (PFS), and overall survival were evaluated by SPSS.

Results: There was a significant difference in tumor size between the two groups, with larger tumors in the calcification group than the control group, and the proportion of patients in the calcification group with tumors of >5 cm was 20.4% vs 17.2% in the control group (P=0.041). The proportion of patients with lymph node metastasis in the calcification group was higher than that of the control group (35% vs 27.9%, P=0.027). The recurrence rate in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) patients with microcalcification was higher than that in the control group (P=0.035 and 0.044). BMP-2 expression was higher in breast cancer tissues, especially in breast cancer tissues with microcalcifications. The recurrence rate in the BMP-2(+) group was higher than that in the BMP-2(-) group both in DCIS and IDC (P=0.044 and 0.049). Microcalcifications and the positive expression of BMP-2 were independent factors affecting the PFS of the breast cancer patients.

Conclusion: Through the analysis of this study, it was found that the prognosis of the patients with microcalcification was relatively poor. BMP-2 was highly expressed in the breast cancer with microcalcification and was associated with poor prognosis.

Keywords: BMP-2; breast cancer; immunohistochemistry prognosis; mammography; microcalcification.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Calcification observed in mammography. Notes: (A) Breast mammography of a patient with DCIS. The arrowhead in the right breast (indicated as RCC) shows a cluster of small and multiform calcification, which suggests malignancy. There was no obvious calcification in the left breast (indicated as LCC). (B) Breast mammography of a patient with IDC. The arrowhead in the right breast (indicated as RCC) shows small and round calcification, which is characteristic of benign calcification. The arrowhead in the left breast (indicated as LCC) shows an irregular mass with small and multiform calcification, which suggests malignancy. Scale of the images is 1:4. Abbreviations: DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma.
Figure 2
Figure 2
The immunohistochemistry of BMP-2 (×200). Notes: (A) Negative BMP-2 expression. (B) Positive BMP-2 expression is indicated by cytoplasmic/membranous staining in breast cancer cells ≥10%.
Figure 3
Figure 3
The PFS and OS of patients with calcification. Notes: The recurrence rate in patients with microcalcification was higher than the control group (A: DCIS, P=0.035; C: IDC, P=0.044). There was no significant difference in OS between the two groups (B: DCIS, P=0.257; D: IDC, P=0.183). Abbreviations: DCIS, ductal carcinoma in situ; IDC, infiltrative ductal carcinoma; OS, overall survival; PFS, progression-free survival.
Figure 4
Figure 4
Immunohistochemistry results. Notes: (A) H&E stain in IDC revealed calcification in the lumen. (B) The expression of E-cadherin, indicative of an epithelial phenotype, is weakened. (C) Partial expression of vimentin, indicative of an interstitial phenotype. (D) Positive BMP-2 expression is indicated by cytoplasmic/membranous staining in breast cancer cells. (E) Positive Runx2 expression is indicated by cell nuclear staining in breast cancer cells. (F) Positive OPN expression is indicated by cytoplasmic/membranous staining in breast cancer cells. Abbreviations: IDC, invasive ductal carcinoma; OPN, osteopontin.
Figure 5
Figure 5
Relationship between expression of BMP-2 and prognosis. Notes: (A) For DCIS, the recurrence rate in the BMP-2(+) group was significantly higher than that in the BMP-2(−) group (P=0.044). (B) For DCIS, there was no significant difference in OS between the two groups (P=0.264). (C) For IDC, the recurrence rate in the BMP-2(+) group was significantly higher than that in the BMP-2(−) group (P=0.049). (D) For IDC, the OS of the BMP-2(+) group was higher than that of the BMP-2(−) group but was not statistically significant (P=0.302). Abbreviations: DCIS, ductal carcinoma in situ; IDC, infiltrative ductal carcinoma; OS, overall survival; PFS, progression-free survival.
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