{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:02:07Z","timestamp":1784523727371,"version":"3.55.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mixed urothelial carcinoma (UC) and small-cell carcinoma (SmCC) of the renal pelvis is a rare but clinically consequential malignancy in which recognition of the neuroendocrine component directly influences diagnosis and treatment. We compared insulinoma-associated protein 1 (INSM1) with traditional neuroendocrine markers and explored clinicopathological correlates of outcome in a retrospective cohort of mixed renal pelvic UC\/SmCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty-seven consecutive patients with histologically confirmed mixed renal pelvic UC\/SmCC were identified from the institutional pathology archive during a prespecified consecutive 5-year accrual window (January 2019 to December 2023). Paired SmCC and urothelial compartments were evaluated separately on 4-\u03bcm formalin-fixed paraffin-embedded sections for INSM1, synaptophysin, chromogranin A, CD56, CK7, GATA3, Ki-67, and p53, using a modified H-score (0\u2013300). Paired marker positivity was compared with the McNemar test, paired quantitative differences with the Wilcoxon signed-rank test, and overall survival was modeled with Kaplan\u2013Meier estimation and Cox proportional hazards regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>INSM1 showed the highest sensitivity for the SmCC compartment, with nuclear positivity in 26 of 27 cases (96.3%; 95% CI, 81.0\u201399.9%), compared with synaptophysin 59.3%, chromogranin A 18.5%, and CD56 85.2%; all paired UC components were INSM1-negative. INSM1 was significantly more sensitive than synaptophysin (P &amp;lt; 0.01) and chromogranin A (P &amp;lt; 0.001), whereas CD56 did not differ significantly from INSM1 (P\u00a0=\u00a00.375). CK7 and GATA3 were retained exclusively in the UC compartment, and the median Ki-67 index was markedly higher in SmCC than UC (76% vs 24%; P &amp;lt; 0.001). On univariable Cox analysis, advanced pT stage, nodal metastasis, predominant SmCC burden, and higher INSM1 H-score were adversely associated with overall survival, whereas adjuvant chemotherapy was associated with reduced mortality risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>INSM1 is a sensitive and compartment-specific marker for identification of the SmCC component and showed higher sensitivity than synaptophysin and chromogranin A in this cohort, while performing similarly to CD56. Combined with CK7 and GATA3, INSM1 helps delineate the urothelial and neuroendocrine lineages within a single biphasic tumor. Larger multi-institutional cohorts with molecular profiling are needed to validate these exploratory findings and to clarify whether quantitative INSM1 expression carries prognostic relevance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1861172","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T04:21:04Z","timestamp":1784521264000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression and prognostic significance of INSM1 compared with traditional neuroendocrine markers in mixed urothelial and small-cell carcinoma of the renal pelvis"],"prefix":"10.3389","volume":"16","author":[{"given":"Ji","family":"Li","sequence":"first","affiliation":[{"name":"Clinical Pathology Diagnosis Center, The Second Affiliated Hospital of Qiqihar Medical University","place":["Qiqihar, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Jiamusi University","place":["Jiamusi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lunbi","family":"Wu","sequence":"additional","affiliation":[{"name":"Clinical Pathology Diagnosis Center, The Second Affiliated Hospital of Qiqihar Medical University","place":["Qiqihar, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s12894-021-00876-7","article-title":"The incidence and prevalence of upper tract urothelial carcinoma: a systematic review","volume":"21","author":"Soualhi","year":"2021","journal-title":"BMC 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