Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma

"Purpose: Expression profiling studies classified breast carcinomas into estrogen receptor (ER)+/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with poor outcomes. Currently, there exist clinical assays that identify ER+/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors. Experimental Design: To identify an immunohistochemical profile for breast basal-like tumors, we collected a series of known basal-like tumors and tested them for protein patterns that are characteristic of this subtype. Next, we examined the significance of these protein patterns using tissue microarrays and evaluated the prognostic significance of these findings. Results: Using a panel of 21 basal-like tumors, which was determined using gene expression profiles, we saw that this subtype was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4-year mean follow-up, basal cytokeratin expression was associated with low disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins (versus 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers but did not influence prognosis. Conclusions: A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors using standard available clinical tools and shows high specificity. These studies show that many basal-like tumors express HER1, which suggests candidate drugs for evaluation in these patients.

Molecular portraits of human breast tumours

Human breast tumours are diverse in their natural history and in their responsiveness to treatments1. Variation in transcriptional programs accounts for much of the biological diversity of human cells and tumours. In each cell, signal transduction and regulatory systems transduce information from the cell's identity to its environmental status, thereby controlling the level of expression of every gene in the genome. Here we have characterized variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. These patterns provided a distinctive molecular portrait of each tumour. Twenty of the tumours were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumours were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumour samples from the same individual were almost always more similar to each other than either was to any other sample. Sets of co-expressed genes were identi®ed for which variation in messenger RNA levels could be related to speci®c features of physiological variation. The tumours could be classi®ed into subtypes distinguished by pervasive differences in their gene expression patterns

Aligning the Goals of Learning Analytics with its Research Scholarship: An Open Peer Commentary Approach

To promote cross-community dialogue on matters of significance within the field of learning analytics], we as editors-in- chief of the Journal of Learning Analytics have introduced a section for papers that are open to peer commentary. The first of these papers, “A LAK of Direction: Misalignment Between the Goals of Learning Analytics and its Research Scholarship” by Motz et al. (2023), appeared in the journal’s early access section in March 2023, a few days before the start of the 13th International Learning Analytics and Knowledge Conference (LAK ’23). “A LAK of Direction” takes as its starting point the definition of learning analytics used in the call for papers of the first LAK conference (LAK ’11) and used since then by the Society for Learning Analytics Research (SoLAR): “Learning analytics is the measurement, collection, analysis and reporting of data about learners and their contexts, for purposes of understanding and optimizing learning and the environments in which it occurs” (Long & Siemens, 2011, p. 24). Following the conference, an invitation to submit proposals for commentaries on the paper was released, and 12 of these proposals were accepted. This paper brings those commentaries togethe

Aligning the Goals of Learning Analytics with its Research Scholarship: An Open Peer Commentary Approach

To promote cross-community dialogue on matters of significance within the field of learning analytics (LA), we as editors-in-chief of the Journal of Learning Analytics (JLA) have introduced a section for papers that are open to peer commentary. An invitation to submit proposals for commentaries on the paper was released, and 12 of these proposals were accepted. The 26 authors of the accepted commentaries are based in Europe, North America, and Australia. They range in experience from PhD students and early-career researchers to some of the longest-standing, most senior members of the learning analytics community. This paper brings those commentaries together, and we recommend reading it as a companion piece to the original paper by Motz et al. (2023), which also appears in this issu

Comparison of Single versus Double Lateral Plating in Treatment of Feline Ilial Fractures Using Veterinary Cuttable Plates

OBJECTIVE:  The aim of this study was to compare the frequency of implant failure and the extent of pelvic canal narrowing associated with the fixation of ilial fractures in cats with a single veterinary cuttable plate (SLP) or double veterinary cuttable plates (DLP) applied to the lateral surface of the ilium. STUDY DESIGN:  Radiographic evaluation of feline ilial fractures plated laterally using SLP or DLP. Pelvic canal narrowing directly postoperatively and at 6 weeks follow-up was objectively measured using the sacral index (SI). Radiographs were evaluated for implant failure and fracture healing. RESULTS:  Seventy-seven cats satisfied the inclusion criteria. Twenty-nine fractures were treated with a SLP and 48 with DLP. Implant failure occurred significantly more (p = 0.001) in the SLP group (14/29) compared with the DLP group (6/48). Follow-up SI was significantly different between the two groups (p = 0.048, SLP median: 1.0 range: 0.83-2.4, DLP median: 0.98; range: 0.76-1.45). Median change in SI was -0.04 (range: -1.4 to 0.05) in the SLP group and 0.0 (range: -0.23 to 0.23) in the DLP group. This difference was significantly different (p = 0.031). CONCLUSION:  DLP leads to significantly less implant failure and significantly less pelvic canal narrowing compared with SLP. This difference in pelvic canal narrowing was small and the clinical relevance remains unclear

Comparison of Single versus Double Lateral Plating in Treatment of Feline Ilial Fractures Using Veterinary Cuttable Plates

OBJECTIVE:  The aim of this study was to compare the frequency of implant failure and the extent of pelvic canal narrowing associated with the fixation of ilial fractures in cats with a single veterinary cuttable plate (SLP) or double veterinary cuttable plates (DLP) applied to the lateral surface of the ilium. STUDY DESIGN:  Radiographic evaluation of feline ilial fractures plated laterally using SLP or DLP. Pelvic canal narrowing directly postoperatively and at 6 weeks follow-up was objectively measured using the sacral index (SI). Radiographs were evaluated for implant failure and fracture healing. RESULTS:  Seventy-seven cats satisfied the inclusion criteria. Twenty-nine fractures were treated with a SLP and 48 with DLP. Implant failure occurred significantly more (p = 0.001) in the SLP group (14/29) compared with the DLP group (6/48). Follow-up SI was significantly different between the two groups (p = 0.048, SLP median: 1.0 range: 0.83-2.4, DLP median: 0.98; range: 0.76-1.45). Median change in SI was -0.04 (range: -1.4 to 0.05) in the SLP group and 0.0 (range: -0.23 to 0.23) in the DLP group. This difference was significantly different (p = 0.031). CONCLUSION:  DLP leads to significantly less implant failure and significantly less pelvic canal narrowing compared with SLP. This difference in pelvic canal narrowing was small and the clinical relevance remains unclear