Robert M. Quinlan

IMP3 is a novel biomarker for triple negative invasive mammary carcinoma associated with a more aggressive phenotype

IMP3, an oncofetal protein, is a member of the insulin-like growth factor-II (IGF-II) mRNA-binding protein family. Its relevance as a novel biomarker in lung, pancreatic, renal, and cervical adenocarcinoma was recently revealed. However, its role in breast carcinogenesis and tumor progression is not yet established. Basal-like carcinoma was initially identified by gene expression profiling. It accounts for 15% to 30% of all breast cancers. These tumors express basal epithelial markers including cytokeratin 5 but lack expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), therefore, are often referred to as triple negative breast cancer. They have been found to be associated with a worse overall and disease-free survival. In this retrospective study, we examined the IMP3 expression in invasive ductal carcinoma of the breast and correlated its expression with morphological and biologic prognostic factors. The study group comprised 138 cases of invasive ductal carcinoma retrieved from the surgical pathologic files for a 10-year period from 1997 to 2006. Survival data and clinical stage were available on all 138 patients. Tumor characteristics including size, grade, lymphovascular invasion, necrosis, lymph node metastasis, estrogen receptor, progesterone receptor, and HER2 status were obtained from pathologic reports. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue using mouse monoclonal antibody against IMP3 and CK5/6. Of the 138 breast cancer cases, IMP3 expression was seen in 45 (33%). Twenty-five of the IMP3+ cases were triple negative. We found significant correlation between IMP3 expression and higher grade (P = .001), necrosis (P< .0001) triple negative, and CK5/6 expression (P < .0001 for each). Cox multivariate analysis showed a hazard ratio of IMP3 expression at 3.14 (P = .05). IMP3 is a novel biomarker for triple negative (basal-like) invasive mammary carcinoma, and its expression is associated with a more aggressive phenotype and decreased overall survival.

Insulin-Like Growth Factor mRNA Binding Protein 3 (IMP3) is Differentially Expressed in Benign and Malignant Follicular Patterned Thyroid Tumors

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 Hashimotos 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.

Multimodal optical imaging for detecting breast cancer

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 cellular-level 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.

Eight Hundred Cholecystectomies: A Plea for Many Fewer Drains

Routine drainage of cholecystectomy wounds has been abandoned at this community hospital and drainage is done only for excessive ooze of bile or blood; for acute suppurative, gangrenous, or perforated cholecystitis; and for extremely debilitated or immunosuppressed patients. In 800 consecutive cholecystectomies, no drain was used in 574 patients (71.7%). There was no increase in complications and no mortality in the undrained patients. There was a substantial decrease in the length of postoperative hospitalization, with 53% of the undrained patients discharged by the sixth postoperative day, compared to only 8.3% of those with drains. It is urged that gallbladder wounds be drained only for specific indications.

Polarization Sensitive Multimodal Imaging for Detecting Breast Cancer

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.

Surgical-Office-Based Versus Radiology-Referral-Based Breast Ultrasonography : A Comparison of Efficiency, Cost, and Patient Satisfaction

BACKGROUND The differences in efficiency, cost of care, and patient satisfaction between surgical-office-based (SB) breast ultrasonography by the surgeon and radiology-referral-based (RB) ultrasonography by the radiologist in the workup of lumps and imaging abnormalities have not been computed. STUDY DESIGN Charts of 61 consecutive patients requiring breast ultrasonography at the Comprehensive Breast Center from October through December 2005 were evaluated. The SB ultrasonography approach was compared with the RB approach. Matching variables were patient age, presenting complaint, Gail risk score, ultrasonography findings, interventional procedure, and histopathology reports. Outcomes variables were efficiency (time from presentation and establishment of diagnosis), cost of care, and patient satisfaction. RESULTS Twenty-nine patients had RB and 32 had SB breast ultrasonography. The RB and SB groups were similar in age, Gail risk, and ultrasonography findings. Median time to establish diagnosis in the RB group was 23 days, versus 1 day in the SB group (p < 0.0001). Median cost of care in the RB versus SB group was

Effect of Paget's Disease on Survival in Breast Cancer: An Exploratory Study

659.00 versus

Commonwealth of Massachusetts Board of Registration in Medicine Expert Panel on Immediate Implant-Based Breast Reconstruction Following Mastectomy for Cancer: Executive Summary, June 2011

369.50 (p = 0.253), and net revenue generated was

Delineating breast ductal carcinoma using combined dye-enhanced wide-field polarization imaging and optical coherence tomography

85.00 versus

Superiority of sonographic hematoma guided resection of mammogram only visible breast cancer: wire localization should be an exception--not the rule

195.00 (p = 0.005), respectively. Forty-nine of 61 (80.3%) patients responded to the satisfaction survey. Forty-seven of 49 (96%) patients expect the diagnosis to be established within 48 hours. Twenty-eight of 28 (100%) patients in the SB group regarded their imaging study to be efficient, versus 5 of 21 patients in the RB group (p = 0.005); 16 of 21 in the RB group versus 26 of 28 in the SB group thought they adequately understood the ultrasonography findings at the time of study (p = 0.051). Twenty-four (86%) SB patients versus 14 (67%) RB patients rated overall experience as excellent (p = 0.055). CONCLUSIONS SB breast ultrasonography is an efficient, cost-effective, and patient-friendly approach to breast problems.