Translational Potential of Fluorescence Polarization for Breast Cancer Cytopathology.

Breast cancer is the most common malignancy in women. The standard of care for diagnosis involves invasive core needle biopsy followed by time-consuming histopathological evaluation. A rapid, accurate, and minimally invasive method to diagnose breast cancer would be invaluable. Therefore, this clinical study investigated the fluorescence polarization (Fpol) of the cytological stain methylene blue (MB) for the quantitative detection of breast cancer in fine needle aspiration (FNA) specimens. Cancerous, benign, and normal cells were aspirated from excess breast tissues immediately following surgery. The cells were stained in aqueous MB solution (0.05 mg/mL) and imaged using multimodal confocal microscopy. The system provided MB Fpol and fluorescence emission images of the cells. Results from optical imaging were compared to clinical histopathology. In total, we imaged and analyzed 3808 cells from 44 breast FNAs. Fpol images displayed quantitative contrast between cancerous and noncancerous cells, whereas fluorescence emission images showed the morphological features comparable to cytology. Statistical analysis demonstrated that MB Fpol is significantly higher (p < 0.0001) in malignant vs. benign/normal cells. It also revealed a correlation between MB Fpol values and tumor grade. The results indicate that MB Fpol could provide a reliable, quantitative diagnostic marker for breast cancer at the cellular level.

Savi-Scout Radar Localization: Transitioning From the Traditional Wire Localization to Wireless Technology for Surgical Guidance at Lumpectomies.

Breast-conserving surgery or lumpectomy requires localization of the lesion prior to surgery, which is traditionally accomplished by imaging-guided wire localization. Over the last decade, alternatives to wire localization have emerged. This work reviews the literature on one such wireless technology, SaviScout radar (SSR) system, and shares our experience with using this technology for presurgical tumor localization. The SSR surgical guidance system is non-radioactive. The radiologist implants a reflector device in the breast under mammography or ultrasound guidance at any time prior to surgery. The placement of this reflector can be confirmed from the cadence of a handheld percutaneous probe of a handpiece and console system. Results from several studies show that the surgical outcomes from SSR and wire-localization are similar. SSR provides operational advantages as the scheduling for reflector placement by radiologists is decoupled from surgery, but at an increased cost compared to wire-localization.

Ultrasound Imaging Morphology is Associated with Biological Behavior in Invasive Ductal Carcinoma of the Breast.

OBJECTIVES: Ultrasound (US) is commonly used for diagnostic evaluation of breast lesions. The objective of this study was to investigate the association between US imaging morphology from routine radiologists' interpretation and biological behavior such as receptor status and tumor grade determined from histopathology in invasive ductal carcinoma (IDC). MATERIAL AND METHODS: This retrospective study included 453 patients with pathology-verified diagnosis of IDC who had undergone US imaging and had surgery over a 5-year period. US and surgical pathology reports were reviewed and compiled. Correlation analyses and age-adjusted multivariable models were used to determine the association between US imaging morphology and receptor status, tumor grade, and germ line mutation of the breast cancer genes (BRCA1 and BRCA2). The odds ratio (OR), area under receiver operating characteristic curve (AUC), and 95% confidence intervals (CI) were obtained. RESULTS: The likelihood for high-grade cancer increased with size (OR: 1.066; CI: 1.042-1.091) and hypo-echogenicity (OR: 2.044; CI: 1.337-3.126), and decreased with angular or spiculated margins (OR: 0.605; CI: 0.393-0.931) and posterior acoustic shadowing (OR: 0.352; CI: 0.238-0.523). These features achieved an AUC of 0.799 (CI: 0.752-0.845) for predicting high-grade tumors. The likelihood for Estrogen Receptor-positive tumors increased with posterior acoustic shadowing (OR: 3.818; CI: 2.206-6.607), angulated or spiculated margins (OR: 2.596; CI: 1.159-5.815) and decreased with US measured tumor size (OR: 0.959; CI: 0.933-0.986) and hypoechoic features (OR: 0.399; CI: 0.198- 0.801), and achieved an AUC of 0.787 (CI: 0.733-0.841). The likelihood for Progesterone Receptor-positive tumors increased with posterior acoustic shadowing (OR: 2.732; CI: 1.744-4.28) and angulated or spiculated margins (OR: 2.618; CI: 1.412-4.852), and decreased with US measured tumor size (OR: 0.961; CI: 0.937-0.985) and hypoechoic features (OR: 0.571; CI: 0.335-0.975), and achieved an AUC of 0.739 (CI: 0.689-0.790). The likelihood for Human epidermal growth factor receptor 2-positive tumors increased with heterogeneous echo texture (OR: 2.141; CI: 1.17- 3.919) and decreased with angulated or spiculated margins (OR: 0.408; CI: 0.177-0.944), and was marginally associated with hypoechoic features (OR: 2.101; CI: 0.98-4.505) and circumscribed margins (OR: 4.225; CI: 0.919-19.4). The model with the aforementioned four US morphological features and achieved an AUC of 0.686 (CI: 0.614-0.758). The likelihood for triple-negative breast cancers increased with hypo-echogenicity (OR: 2.671; CI: 1.249-5.712) and decreased with posterior acoustic shadowing (OR: 0.287; CI: 0.161-0.513), and achieved an AUC of 0.739 (CI: 0.671- 0.806). No statistical association was observed between US imaging morphology and BRCA mutation. CONCLUSION: In this study of over 450 IDCs, significant statistical associations between tumor grade and receptor status with US imaging morphology were observed and could serve as a surrogate imaging marker for the biological behavior of the tumor.

Glypican-3: a novel diagnostic marker for hepatocellular carcinoma and more.

Glypican-3 (GPC3) is a heparan sulfate proteoglycan that plays an important role in cell growth and differentiation. GPC3 function is tissue dependent. In some tissues, GPC3 acts as a tumor suppressor gene, whereas in others, it acts as an oncofetal protein. Studies have shown that GPC3 is a reliable marker for hepatocellular carcinoma. The sensitivity and specificity exceeds both alpha-fetoprotein and hepatocyte-paraffin1. GPC3 immunohistochemistry can aid in the differentiation of testicular germ cell tumors, being expressed in all yolk sac tumors but not in seminomas. GPC3 expression has also been identified in some squamous cell carcinomas of the lung and clear cell carcinomas of the ovary. The role of GPC3 in melanomas is still controversial. This article reviews the current information on the application of GPC3 immunostaining in surgical pathology and cytology.