Editors: Rouzan Karabakhtsian, MD, PhD, professor of pathology and director of the Women’s Health Pathology Fellowship, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; S. Emily Bachert, MD, associate pathologist, Brigham and Women’s Hospital, Boston; Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; Divya Sharma, MD, associate professor, Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center; and Paula Toro, MD, pathology resident, Cleveland Clinic.
ARX, PDX1, ISL1, and CDX2 expression to distinguish subgroups of pancreatic neuroendocrine tumors
May 2025—Many pancreatic neuroendocrine tumors fall into two major prognostic subtypes based on DAXX/ATRX-induced alternative lengthening of the telomerase phenotype and alpha- and beta-cell-like epigenomic profiles. However, some do not fit into either subtype. Furthermore, despite advanced genotyping, pancreatic neuroendocrine tumors (PanNET) are generally not well characterized in terms of their histologic and hormonal phenotypes. The authors conducted a study to identify new subgroups of PanNET by extending transcription factor signatures and investigating their correlation with histologic, hormonal, molecular, and prognostic findings. One hundred eighty-five PanNET (165 nonfunctioning and 20 functioning), resected between 1996 and 2023, were classified into the subgroups A1, A2, B, C, and D. They were classified using cluster analysis based on ARX, PDX1, islet-1 (ISL1), and CDX2 expression. They were also correlated with trabecular versus solid histology; expression of insulin, glucagon, polypeptide, somatostatin, serotonin, gastrin, calcitonin, adrenocorticotropic hormone (ACTH), DAXX/ATRX, and MEN1; alternative lengthening of telomeres by FISH; and disease-free survival. Groups A1 (46 percent, ARX+/ISL1+/PDX1−/CDX2−) and A2 (15 percent, ARX+/ISL1+/PDX1+/CDX2−) showed trabecular histology and glucagon/polypeptide expression, with A2 also showing gastrin expression. Group B (18 percent, PDX1+/ISL1+/ARX−/CDX2−) showed solid histology, as well as insulin and somatostatin expression. It included all insulinomas and had the best outcome. Group C (15 percent, ARX−/PDX1−/ISL1−/CDX2−) showed solid histology and frequent expression of serotonin, calcitonin, and ACTH. Group D (five percent, PDX1+/CDX2+/ISL1−/ARX−) showed solid histology, expressed ACTH/serotonin, and was an independent poor prognosticator for disease-free survival. In summary, differential expression of ARX, PDX1, ISL1, and CDX2 stratified PanNET into five subgroups with different histologies, hormone expressions, and outcomes. Subgroups A1 and A2 resembled the alpha-cell-like type, and subgroup B resembled the beta-cell-like type. Subgroup C, which had almost no transcription factor signature, was unclear in cell lineage, whereas the PDX+/CDX2+ signature of subgroup D suggested a pancreatic/intestinal cell lineage. The authors concluded that assigning PanNET to the subgroups A to D may help establish a diagnosis, predict outcome, and guide treatment.
Moser E, Ura A, Vogel L, et al. ARX, PDX1, ISL1, and CDX2 expression distinguishes 5 subgroups of pancreatic neuroendocrine tumors with correlations to histology, hormone expression, and outcome. Mod Pathol. 2024;37(11). doi.org/10.1016/j.modpat.2024.100595
Correspondence: Dr. Atsuko Kasajima at atsuko.kasajima@tum.de
HER2-low prevalence among Hispanic and Latino women with breast cancer
The category HER2-low has garnered significant attention in the treatment of HER2-negative breast cancer. The authors conducted a study to determine the prevalence of HER2-low expression in Hispanic and Latino women with breast cancer. They searched the Embase, LILACS (Latin America and the Caribbean Literature on Health Sciences), and Medline databases for articles reporting the expression of HER2 IHC with scores of 0, 1+, 2+, or 3+, with equivocal cases (2+) confirmed through in situ hybridization (ISH). The authors included in their study 12 articles that assessed studies comprising a total of 73,467 people. The prevalence of HER2-zero, HER2-low, and HER2-positive cases among all breast cancers (0, 1+, 2+/ISH−, 2+/ISH+, and 3+) was 45, 32, and 23 percent, respectively. The prevalence of HER2-zero and HER2-low expression among negative cases (0, 1+, and 2+/ISH−) was 53 and 47 percent, respectively. The authors concluded that a noteworthy percentage of Hispanic and Latino women would benefit from HER2-targeted therapies, even in HER2-negative cases. Additional research on the prevalence of HER2-low tumors across a wider range of Latin American countries is necessary to further understanding of the molecular epidemiology of this biomarker within the Hispanic and Latino population.
Mendivelso-González DF, Clavijo Cabezas D, Montoya L, et al. HER2-low prevalence among Hispanic/Latino women with breast cancer: A systematic review and meta-analysis. PLoS One. 2024;19(12). doi.org/10.1371/journal.pone0315287
Correspondence: Dr. Rafael Parra-Medina at rafa.parram@gmail.com
Perceptions of pathology report access via portals among patients with solid tumors
Patients can immediately review pathology reports via online health portals. The authors conducted a study to better understand oncology patients’ perceptions regarding the ability to access the content of pathology reports via such portals. Semistructured interviews were conducted with oncology patients who had breast, endocrine, gastrointestinal, genitourinary, or thoracic malignancies. The study involved statistically analyzing patient demographic information, cancer type, responses to questions, and thematically grouped comments. The number of male and female participants was nearly equal—116 (50.4 percent) female and 114 (49.6 percent) male. Patients who viewed their reports in the portal or had a support person do so (172 of 230; 74.8 percent) differed from those who did not (58 of 230; 25.2 percent) only in their perceptions of the helpfulness (P<.001) of the report. Difficulty understanding medical terminology was the most frequently cited challenge among both those who found the reports helpful (30 of 160; 18.75 percent) and those who did not (31 of 46; 67.4 percent). Most patients (196 of 230; 85.2 percent) preferred that results be released immediately, even if they contained bad news, whereas some (34 of 230; 14.7 percent) would opt out of immediate release for fear of misunderstanding information (11 of 34; 32.4 percent) or receiving distressing information by reading the report (23 of 34; 67.6 percent). The authors concluded that offering more flexibility in portal options, such as giving patients the choice of immediately receiving some, but not all, results, as well as providing patient-centered pathology reports, educational materials, and tailored support can benefit patients seeking to review their pathology reports in patient portals.
Bo AY, Cheng YC, George B, et al. Online portal use of pathology reports in patients with solid tumors. Arch Pathol Lab Med. 2024. doi.org/10.5858/arpa.2024-0327-OA
Correspondence: Dr. Julie M. Jorns at jjorns@mcw.edu