Breast Heterogeneity: Obstacles to Developing Universal Biomarkers of Breast Cancer Initiation and Progression.

BACKGROUND: Predicting outcomes and response to therapy through biomarkers is a major challenge in cancer research. In previous studies, we suggested that inappropriate "normal" tissue samples used for comparison with tumors, inter-individual heterogeneity in gene expression, and genetic ancestry all influence biomarker expression in tumors. The aim of this study was to investigate these factors in breast cancer using breast tissues from healthy women and normal tissue adjacent to tumor (NAT) with matrix metalloproteinase 7 (MMP7) as a candidate biomarker. STUDY DESIGN: RNA sequencing was performed on primary luminal progenitor cells from healthy breast, NATs, and tumors to identify transcriptomes enriched in NATs and breast cancer. Expression of select genes was validated via quantitative reverse transcription polymerase chain reaction of RNA and via immunohistochemistry of a tissue microarray of normal, NAT, and tumor samples of different genetic ancestry. RESULTS: Twenty-six genes were significantly overexpressed in NATs and tumors compared with healthy controls at messenger RNA level and formed a para-inflammatory network. MMP7 had the greatest expression in tumor cells, with upregulation confirmed by quantitative reverse transcription polymerase chain reaction. Tumor-enriched but not NAT-enriched expression of MMP7 compared with healthy controls was reproduced at protein levels. When stratified by genetic ancestry, tumor-specific increase of MMP7 reached statistical significance in women of European ancestry. CONCLUSIONS: Transcriptome differences across healthy, NAT, and tumor tissue in breast cancer demonstrate an active para-inflammatory network in NATs and indicate unsuitability of NATs as "normal controls" in biomarker discovery. The discordance between transcriptomic and proteomic MMP7 expression in NATs and the influence of genetic ancestry on its protein expression highlight the complexity in developing universally acceptable biomarkers of breast cancer and the importance of genetic ancestry in biomarker development.

Diagnosis and treatment of cystic pancreatic tumors.

Cystic pancreatic tumors (CPTs) have more frequently been identified in the last decade because of increased use of cross-sectional abdominal imaging. Although serous CPTs follow an indolent course and do not necessarily require surgical resection or long-term follow-up, mucinous CPTs (mucinous cystic neoplasms and intraductal papillary mucinous neoplasms) have a greater risk for malignancy. Although most CPTs are initially detected with imaging modalities such as computed tomography or magnetic resonance imaging, these tests alone rarely permit an accurate clinical diagnosis. Endoscopic ultrasound and endoscopic ultrasound-guided, fine-needle aspiration allow real-time examination and biopsy analysis of CPTs, which increases diagnostic accuracy because cytopathology features and tumor markers in cyst fluid can be analyzed. Management of patients with mucinous CPTs by surgery or imaging surveillance is controversial, partially because of limited information about disease progression and the complexities of surgical resection. We review approaches to diagnosis and management of common CPTs.

Left-sided pancreatectomy: a multicenter comparison of laparoscopic and open approaches.

OBJECTIVES: To compare perioperative outcomes of laparoscopic left-sided pancreatectomy (LLP) with traditional open left-sided pancreatectomy (OLP) in a multicenter experience. SUMMARY AND BACKGROUND DATA: LLP is being performed more commonly with limited data comparing results with outcomes from OLP. METHODS: Data from 8 centers were combined for all cases performed between 2002-2006. OLP and LLP cohorts were matched by age, American Society of Anesthesiologists, resected pancreas length, tumor size, and diagnosis. Multivariate analysis was performed using binary logistic regression. RESULTS: Six hundred sixty-seven LPs were performed, with 159 (24%) attempted laparoscopically. Indications were solid lesion in 307 (46%), cystic in 295 (44%), and pancreatitis in 65 (10%) cases. Positive margins occurred in 51 (8%) cases, 335 (50%) had complications, and significant leaks occurred in 108 (16%). Conversion to OLP occurred in 20 (13%) of the LLPs. In the matched comparison, 200 OLPs were compared with 142 LLPs. There were no differences in positive margin rates (8% vs. 7%, P = 0.8), operative times (216 vs. 230 minutes, P = 0.3), or leak rates (18% vs. 11%, P = 0.1). LLP patients had lower average blood loss (357 vs. 588 mL, P < 0.01), fewer complications (40% vs. 57%, P < 0.01), and shorter hospital stays (5.9 vs. 9.0 days, P < 0.01). By MVA, LLP was an independent factor for shorter hospital stay (P < 0.01, odds ratio 0.33, 95% confidence interval 0.19-0.56). CONCLUSIONS: In selected patients, LLP is associated with less morbidity and shorter LOS than OLP. Pancreatic fistula rates are similar for OLP and LLP. LLP is appropriate for selected patients with left-sided pancreatic pathology.