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Published on: June 12, 2019
Downregulation of gelsolin correlates with the progression to breast carcinoma
J S Winston1, H L Asch, P J Zhang
1Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. janet.winston@roswellpark.org
Abstract:
The actin cytoskeleton underlies several normal cellular functions and is deranged during carcinogenesis. Gelsolin, a multifunctional actin-binding protein, is downregulated in several types of tumors and its abnormal expression is one of the most common defects noted in invasive breast carcinoma (ICA). This study utilizes immunohistochemistry to examine the expression of gelsolin in 95 ICA, 59 ductal carcinoma in situ (DCIS) and 36 benign lesions, including 17 atypical ductal hyperplasia (ADH). Cytoplasmic staining was scored as positive, reduced or negative. Gelsolin expression was then correlated with patient's age, tumor size, histologic grade and lymph node status. All unremarkable breast biopsies, 88% of ADH, 44% of DCIS and 28% of ICA were positive for gelsolin. This represents a significant difference among the groups (p = < 0.0001) and the trend towards reduced gelsolin with the progression to ICA is significantly linear (p = < 0.0001). For invasive carcinoma, patients older than 44 years were significantly more likely to have decreased expression of gelsolin than patients 44 years old and younger (p = 0.007). Bivariate analysis showed no correlation of gelsolin expression with lymph node status (p = 0.62), tumor size (p = 0.10), histologic grade (p = 0.42), estrogen receptor status (p = 1.0) or other clinicopathologic parameters. In clinical follow-up, there were 18 breast tumor related deaths within a median follow-up time of 4.2 years. Survival analysis indicated that the level of gelsolin expression may be associated with survival (p = 0.06). In summary, the frequency of gelsolin deficiency increases significantly with progression from ADH to DCIS to ICA. Additionally, gelsolin expression may be an independent marker of prognosis.
Insights
Gelsolin deficiency increases with breast cancer progression. Reduced gelsolin expression in invasive breast carcinoma may indicate a poorer prognosis, highlighting its potential as a diagnostic marker.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- The actin cytoskeleton is crucial for cellular functions and its disruption is linked to cancer.
- Gelsolin, an actin-binding protein, is often downregulated in tumors, with abnormal expression common in invasive breast carcinoma (ICA).
Purpose of the Study:
- To investigate gelsolin expression levels in various stages of breast lesions, including atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and ICA.
- To correlate gelsolin expression with clinicopathologic parameters and patient survival.
Main Methods:
- Immunohistochemistry was used to assess cytoplasmic gelsolin expression (positive, reduced, or negative) in 95 ICA, 59 DCIS, and 36 benign breast lesions.
- Gelsolin expression was correlated with patient age, tumor size, histologic grade, lymph node status, and survival data.
Main Results:
- Gelsolin was expressed in all normal breast tissues, 88% of ADH, 44% of DCIS, and 28% of ICA, showing a significant decrease with cancer progression (p < 0.0001).
- Decreased gelsolin expression was more common in invasive breast carcinoma patients over 44 years old (p = 0.007).
- Gelsolin expression did not correlate with lymph node status, tumor size, histologic grade, or estrogen receptor status.
Conclusions:
- Gelsolin deficiency significantly increases with the progression from ADH to DCIS to ICA.
- Reduced gelsolin expression may serve as an independent prognostic marker for invasive breast carcinoma, potentially impacting patient survival (p = 0.06).
