No abstract

Intraoperative delineation of breast cancer is a significant problem in surgical oncology. A reliable method for demarcation of malignant breast tissue during surgery would reduce the re-excision rate due to positive margins. We present a novel method of identifying breast cancer margins using combined dye-enhanced wide-field fluorescence polarization imaging for en face cancer margins and polarization-sensitive (PS) optical coherence tomography (OCT) for cross-sectional evaluation. Tumor specimens were collected following breast surgery, stained with methylene blue, and imaged. Wide-field fluorescence polarization images were excited at 640 nm and registered between 660 and 750 nm. Standard and PS OCT images were acquired using a commercial 1,310-nm swept-source system. The imaging results were validated against histopathology. Statistically significant higher fluorescence polarization of cancer as compared with both normal and fibrocystic tumor tissue was measured in all the samples. Fluorescence polarization delineated lateral breast cancer margins with contrast superior to that provided by OCT. However, OCT complemented fluorescence polarization imaging by facilitating cross-sectional inspection of tissue. PS OCT yielded higher contrast between cancer and connective tissue, as compared with standard OCT. Combined PS OCT and fluorescence polarization imaging shows promise for intraoperative delineation of breast cancer. Cancer Res; 74(17); 4685-93. Ó2014 AACR.

Insulin-like growth factor mRNA binding protein 3 (IMP3) is an mRNA-binding protein that regulates transcription of insulin-like growth factor II affecting cell proliferation during embryogenesis. It is highly expressed in carcinomas of the pancreas, stomach, colon, rectum, kidneys, uterine cervix, lung, and ovary. The purpose of our study was to evaluate IMP3 expression in thyroid follicular lesions, to determine whether it has a role in differentiating among these lesions, and to understand their biological relationships. We immunostained 219 thyroid lesions selected from our surgical pathology archives including 14 hyperplastic colloid nodules (CN), 19 Hashimoto's thyroiditis (HT), two Graves disease (GD), ten Hürthle cell adenoma (HCA), 20 follicular adenoma (FA), 37 conventional papillary thyroid carcinoma (PTC), 60 follicular variant of papillary carcinoma (FVPC), 19 Hürthle cell carcinoma (HCC), 32 follicular carcinoma (FC), and six poorly differentiated/anaplastic carcinoma. Immunohistochemistry was performed on formalin-fixed sections using monoclonal antibody to IMP3. Clinicopathological data were also reviewed. In all cases, residual thyroid tissue, CN, HT, GD, HCA, and FA were completely negative for IMP3 staining. Of the 60 FVPC, 23 tumors (38%) were positive for IMP3, with 13 of these (22%) showing very strong staining (3+). Of the 32 FC, 22 tumors (69%) were positive, with seven (22%) showing very strong staining (3+). Furthermore, 33 out of 37 cases (89%) of PTC were negative for IMP3. In all four PTC cases that did stain positive, staining was weak-moderate (1-2+). Similarly, 15 out of 19 cases (79%) of HCC were negative. No significant correlation was found between pathologic tumor characteristics and IMP3 expression in differentiated follicular pattern thyroid carcinoma. With 100% specificity and 69% sensitivity for FC as compared to FA and 100% specificity for FVPC, again compared to FA, IMP3 has the potential to be diagnostically useful in differentiating malignant and benign follicular pattern thyroid lesions. This study also points to a possible common biological relationship between FC and FVPC that requires further investigation.

Abstract. The goal of the study was to evaluate wide-field and high-resolution multimodal optical imaging, including polarization, reflectance, and fluorescence for the intraoperative detection of breast cancer. Lumpectomy specimens were stained with 0.05 mg∕ml aqueous solution of methylene blue (MB) and imaged. Wide-field reflectance images were acquired between 390 and 750 nm. Wide-field fluorescence images were excited at 640 nm and registered between 660 and 750 nm. High resolution confocal reflectance and fluorescence images were excited at 642 nm. Confocal fluorescence images were acquired between 670 nm and 710 nm. After imaging, the specimens were processed for hematoxylin and eosin (H&E) histopathology. Histological slides were compared with wide-field and high-resolution optical images to evaluate correlation of tumor boundaries and cellular morphology, respectively. Fluorescence polarization imaging identified the location, size, and shape of the tumor in all the cases investigated. Averaged fluorescence polarization values of tumor were higher as compared to normal tissue. Statistical analysis confirmed the significance of these differences. Fluorescence confocal imaging enabled cellularlevel resolution. Evaluation and statistical analysis of MB fluorescence polarization values registered from single tumor and normal cells demonstrated higher fluorescence polarization from cancer. Wide-field high-resolution fluorescence and fluorescence polarization imaging shows promise for intraoperative delineation of breast cancers.