Downregulation of gelsolin correlates with the progression to breast carcinoma

The actin cytoskeleton underlies several normal cellular functions and is d eranged during carcinogenesis. Gelsolin, a multifunctional actin-binding pr otein, is downregulated in several types of tumors and its abnormal express ion is one of the most common defects noted in invasive breast carcinoma (I CA). This study utilizes immunohistochemistry to examine the expression of gelsolin in 95 ICA, 59 ductal carcinoma in situ (DCIS) and 36 benign lesion s, including 17 atypical ductal hyperplasia (ADH). Cytoplasmic staining was scored as positive, reduced or negative. Gelsolin expression was then corr elated with patient's age, tumor size, histologic grade and lymph node stat us. All unremarkable breast biopsies, 88% of ADH, 44% of DCIS and 28% of IC A were positive for gelsolin. This represents a significant difference amon g the groups (p = < 0.0001) and the trend towards reduced gelsolin with the progression to ICA is significantly linear (p = < 0.0001). For invasive ca rcinoma, patients older than 44 years were significantly more likely to hav e 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 death s 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 significa ntly with progression from ADH to DCIS to ICA. Additionally, gelsolin expre ssion may be an independent marker of prognosis.