Downregulation of Gelsolin Correlates with the Progression to Breast Carcinoma

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.

The Tumor Antigen Repertoire Identified in Tumor-Bearing Neu Transgenic Mice Predicts Human Tumor Antigens

“…Cytokeratin was also overexpressed in hepatocarcinoma, cervical cancer, and renal cancer, similar tissues as we show here in the murine system (21)(22)(23). Gsn, as a tumor suppressor, is down-regulated significantly in human breast and ovarian cancers (9,11,19,24).…”

Serial analysis of gene expression in normal p53 null mammary epithelium

“…Interestingly, and in agreement with our findings, Gelsolin was found downregulated in several tumor types including breast cancer (Asch et al, 1996). Furthermore, it was observed downregulated at preinvasive stages of human breast carcinogenesis (Winston et al, 2001).…”

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

“…In vivo studies using MMTV-Her2/neu transgenic mice have shown downregulation of gelsolin at the mRNA level in primary mammary tumors in comparison to the normal mammary gland (31). Furthermore, it was showed that gelsolin expression was reduced in human mammary lesions as the disease progressed; atypical ductal hyperplasia!ductal carcinoma in situ!invasive carcinoma (32)(33)(34). However, a previous report indicated that gelsolin levels were increased in the plasma of breast cancer patients (35), suggesting the role of gelsolin in carcinogenesis needs to be further investigated.…”