The significance of enhancer of zeste homolog 2 (EZH2) expression in spindle cell lesions of the breast.

Spindle cell lesions of the breast are rare entities and pose a diagnostic challenge for pathologists due to overlapping morphologic and immunohistochemical features. We evaluated EZH2 expression in various benign (fibromatosis (n = 8), myofibroblastoma (n = 7), neurofibroma (n = 1), nodular fasciitis (n = 5), benign phyllodes tumor (n = 18)) and malignant (malignant phyllodes tumor (n = 8), metaplastic breast carcinoma (n = 16) and angiosarcoma (n = 8)) spindle cell lesions as a potential diagnostic and therapeutic marker. The EZH2 expression was evaluated semi-quantitatively to categorize the cases as 'low' and 'high' expression. All benign lesions showed low EZH2 expression, whereas high EZH2 expression was observed in the majority (28/32; 88%) of malignant lesions. The study results suggest that EZH2 may be used both as an additional diagnostic tool to reach an accurate diagnosis of the spindle cell lesions of the breast and as a therapeutic target for the malignant lesions.

Benign and borderline phyllodes tumors of the breast: Clinicopathologic analysis of 205 cases with emphasis on the surgical margin status and local recurrence rate.

BACKGROUND: The management of benign and borderline phyllodes tumors of the breast with a positive surgical margin is still controversial. Our aim in this study was to evaluate the impact of surgical margin status on the local recurrence rate of benign and borderline phyllodes tumors. METHODS: We reviewed 205 phyllodes tumors (191 benign, 14 borderline) that were surgically excised at our hospital between 2005 and 2019. Follow-up information extending to at least 6 months after surgery was retrieved from the clinical, radiology, and pathology records. RESULTS: The initial surgical margin was negative in 54 (26%) cases, close (≤ 1 mm) in 29 (14%) cases, and positive in 122 (60%) cases. Approximately half of the cases with a close margin and two-third of the cases with a positive margin underwent re-excision to obtain negative margins. Three (2.3%) local recurrences were observed among 131 cases with follow-up information, all three with benign phyllodes tumor. Of these three patients, one had a positive final margin, and two had negative final margins. There was no significant difference in the rate of local recurrence between PT with a positive surgical margin versus a close and negative margin. CONCLUSION: The study results suggest that close clinical and radiologic follow-up may provide a better course of management rather than re-excision when managing positive margins in benign and borderline phyllodes tumors.

High EZH2 expression in ductal carcinoma in situ diagnosed on breast core needle biopsy is an independent predictive factor for upgrade on surgical excision.

PURPOSE: Approximately 25 % of DCIS diagnosed on breast core needle biopsy (CNB) is upgraded to invasive carcinoma on surgical excision. Risk factors to predict the upgrade on excision are not well established, leading many patients to be over or under-treated. EZH2 was shown to be associated with aggressive behavior of cancer from many sites, including breast cancer. We aimed to analyze EZH2 expression and tumor infiltrating lymphocytes (TILs) in DCIS as predictive factors for an upgrade on excision. METHODS: We assessed EZH2 expression in 34 DCIS cases diagnosed on CNB and upgraded to invasive carcinoma on excision. Then, we compared these cases with 60 control cases that were not upgraded on excision. A staining score for DCIS (0-12) was obtained by multiplying the staining intensity (0-3) and the percentage of positive cells (1-4). The nuclear staining score ≥6 was considered as 'high' expression. RESULTS: 46 of 94 (49 %) DCIS on CNB showed high EZH2 expression. EZH2 expression was directly correlated with TILs density, nuclear grade, HER2 expression, Ki-67 index and negative ER status. On univariate analysis, upgrade on excision was associated with high EZH2 expression, high TILs density, negative ER status and high Ki-67 index. Multivariate analysis revealed the high EZH2 expression as the only independent predictive factor for upgrade on excision. CONCLUSIONS: Our study revealed the high EZH2 expression as the only independent predictive factor for an upgrade on excision. Future studies should focus on the evaluation of EZH2 expression in tumor-microenvironment interaction in terms of diagnostic, treatment and prognostic purposes.

Polymeric Micelles as Carriers for Nerve-Highlighting Fluorescent Probe Delivery.

Nerve damage during surgery is a common morbidity experienced by patients that leaves them with chronic pain and/or loss of function. Currently, no clinically approved imaging technique exists to enhance nerve visualization in the operating room. Fluorescence image-guided surgery has gained in popularity and clinical acceptance over the past decade with a handful of imaging systems approved for clinical use. However, contrast agent development to complement these fluorescence-imaging systems has lagged behind with all currently approved fluorescent agents providing untargeted blood pool information. Nerve-specific fluorophores are known, however translations of these agents to the clinic has been complicated by their lipophilic nature, which necessitates specialized formulation strategies for successful systemic administration. To date the known nerve-specific fluorophores have only been demonstrated preclinically due to the necessity of a dimethyl sulfoxide containing formulation for solubilization. In the current study, a polymeric micellar (PM) formulation strategy was developed for a representative nerve-specific fluorophore from the distyrylbenzene family, BMB. The PM formulation strategy was able to solubilize BMB and demonstrated improved nerve-specific accumulation and fluorescence intensity when the same fluorophore dose was administered to mice utilizing the previous formulation strategy. The success of the PM formulation strategy will be important for moving toward clinical translation of these novel nerve-specific probes as it is nontoxic and biodegradable and has the potential to decrease the necessary dose for imaging while also improving the safety profile.