{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:38:47Z","timestamp":1790105927922,"version":"4.0.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004491","name":"Balikesir \u00dcniversitesi","doi-asserted-by":"publisher","award":["2021-107"],"award-info":[{"award-number":["2021-107"]}],"id":[{"id":"10.13039\/501100004491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study investigates the link between proliferation markers (PCNA, p16, Ki-67) and histopathological factors, exploring their prognostic value in breast cancer patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We analyzed female breast cancer patients who underwent surgery. Data collected included demographics, clinical parameters (hemogram, Ca 15.3, menopause status, etc.), family cancer history, pathology, treatments (neoadjuvant, surgical, oncological), tumor staging, lymph node status, receptor status (ER, PR, cerb-b2), and survival. Paraffin blocks were retrospectively analyzed for PCNA, p16, and Ki-67 expression via immunohistochemical staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PCNA scores showed no association with demographic or clinical features, though a statistically significant inter-marker correlation with p16 was found (both markers increased together). P16 scores were not linked to other parameters aside from Ki-67 (also demonstrating positive correlation). Higher Ki-67 index was associated with decreased ER and PR expression and, importantly, decreased survival. Although a significant correlation was observed between PCNA and p16 expression levels, neither marker demonstrated independent prognostic significance with respect to overall survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although PCNA and p16 expression levels were inter-correlated, neither marker showed an independent association with clinicopathological variables or overall survival in our cohort. In contrast, the Ki-67 index was significantly associated with hormone receptor status, pathological stage, and shorter overall survival, and remains the most informative proliferation marker for prognostic stratification in breast cancer. Further prospective studies with standardized scoring and multivariate analysis are warranted to clarify the prognostic value of PCNA and p16.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1779553","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:21:42Z","timestamp":1784175702000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The prognostic significance of immunohistochemical expressions of proliferating cell nuclear antigen, P16 and Ki-67 in breast cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Ali","family":"Duran","sequence":"first","affiliation":[{"name":"Department of Surgical Oncology, Balikesir Universitesi","place":["Balikesir, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00fcseyin","family":"Pulat","sequence":"additional","affiliation":[{"name":"General Surgery Clinic, TC Saglik Bakanligi 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