Pathologic assessment of endoscopic resection specimens with superficial carcinoma of the esophagus: current practice and practical issues.

Endoscopic resection (ER) has become the first-line therapy for early esophageal cancer and offers a treatment alternative to surgery, owing to less morbidity and better quality of life. ER techniques include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). EMR is faster, simpler, and cheaper than ESD, but limited by its ability to resect lesions larger than 1.5 centimeters. Piecemeal EMR has limitations, including a high local recurrence rate and a suboptimal specimen for an accurate pathologic assessment. ESD, on the other hand, allows en bloc resections with negative (R0) margins, irrespective of lesion size, providing an excellent pathologic specimen, however, is technically challenging with a higher risk of complications. The evaluation of ER specimens in pathology varies slightly from institution to institution. Our review summarizes the current practices and issues in the pathologic assessment of esophageal ER specimens, which highlights the necessity of a systematic approach and standardization of both macroscopic and microscopic evaluation. There is a need for a comprehensive and standardized pathology report that will allow for uniform terminology for endoscopists, surgeons, and pathologists, which, in turn, will result in better treatment guidance

SETER/PR: a robust 18-gene predictor for sensitivity to endocrine therapy for metastatic breast cancer

There is a clinical need to predict sensitivity of metastatic hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer to endocrine therapy, and targeted RNA sequencing (RNAseq) offers diagnostic potential to measure both transcriptional activity and functional mutation. We developed the SETER/PR index to measure gene expression microarray probe sets that were correlated with hormone receptors (ESR1 and PGR) and robust to preanalytical and analytical influences. We tested SETER/PR index in biopsies of metastastic HR+/HER2− breast cancer against the treatment outcomes in 140 patients. Then we customized the SETER/PR assay to measure 18 informative, 10 reference transcripts, and sequence the ligand-binding domain (LBD) of ESR1 using droplet-based targeted RNAseq, and tested that in residual RNA from 53 patients. Higher SETER/PR index in metastatic samples predicted longer PFS and OS when patients received endocrine therapy as next treatment, even after adjustment for clinical-pathologic risk factors (PFS: HR 0.534, 95% CI 0.299 to 0.955, p = 0.035; OS: HR 0.315, 95% CI 0.157 to 0.631, p = 0.001). Mutated ESR1 LBD was detected in 8/53 (15%) of metastases, involving 1−98% of ESR1 transcripts (all had high SETER/PR index). A signature based on probe sets with good preanalytical and analytical performance facilitated our customization of an accurate targeted RNAseq assay to measure both phenotype and genotype of ER-related transcription. Elevated SETER/PR was associated with prolonged sensitivity to endocrine therapy in patients with metastatic HR+/HER2− breast cancer, especially in the absence of mutated ESR1 transcript.SCOPUS: ar.jinfo:eu-repo/semantics/publishe