{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:42:40Z","timestamp":1790678560975,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/ http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p>Serous tubal intraepithelial carcinoma (STIC) is the fallopian tube precursor lesion for most cases of pelvic high-grade serous carcinoma (HGSC). To date, the morphologic, molecular, and clinical heterogeneity of STIC and a less atypical putative precursor lesion, termed serous tubal intraepithelial lesion, has not been well characterized. Better understanding of precursor heterogeneity could impact the clinical management of women with incidental STICs (without concurrent carcinoma) identified in cases of prophylactic or opportunistic salpingectomy. This study analyzed morphologic and molecular features of 171 STICs and 21 serous tubal intraepithelial lesions. We assessed their histologic features, Ki-67 and p53 staining patterns, and genome-wide DNA copy number alterations. We classified all precursor lesions into 2 morphologic subtypes, one with a flat surface (Flat) and the other characterized by budding, loosely adherent, or detached (BLAD) morphology. On the basis of pathology review by a panel of 8 gynecologic pathologists, we found 87 BLAD, 96 Flat, and 9 indeterminate lesions. As compared with Flat lesions, BLAD lesions were more frequently diagnostic of STIC (<jats:italic toggle=\"yes\">P<\/jats:italic>&lt;0.0001) and were found concurrently with HGSC (<jats:italic toggle=\"yes\">P<\/jats:italic>&lt;0.0001). BLAD morphology was also characterized by higher Ki-67 proliferation index (<jats:italic toggle=\"yes\">P<\/jats:italic>&lt;0.0001), presence of epithelial stratification (<jats:italic toggle=\"yes\">P<\/jats:italic>&lt;0.0001), and increased lymphocyte density (<jats:italic toggle=\"yes\">P<\/jats:italic>&lt;0.0001). BLAD lesions also exhibited more frequent DNA copy number gain\/amplification at the <jats:italic toggle=\"yes\">CCNE1<\/jats:italic> or <jats:italic toggle=\"yes\">CMYC<\/jats:italic> loci canonical to HGSCs (<jats:italic toggle=\"yes\">P<\/jats:italic>&lt;0.0001). Both BLAD morphology and STIC diagnoses are independent risk factors for an elevated Ki-67 proliferation index. No correlation was observed between BLAD and Flat lesions with respect to patient age, presence of germline <jats:italic toggle=\"yes\">BRCA1\/2<\/jats:italic> mutation, or p53 staining pattern. These findings suggest that tubal precursor lesions are morphologically and molecularly heterogeneous, laying the foundation for further studies on the pathogenesis of HGSC initiation and identifying histologic features predictive of poor patient outcomes.<\/jats:p>","DOI":"10.1097\/pas.0000000000002187","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T08:00:34Z","timestamp":1706774434000},"page":"475-486","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":35,"title":["Morphologic and Molecular Heterogeneity of High-grade Serous Carcinoma Precursor Lesions"],"prefix":"10.1097","volume":"48","author":[{"given":"Yen-Wei","family":"Chien","sequence":"first","affiliation":[{"name":"Departments of Gynecology and Obstetrics"},{"name":"Department of Oncology, Division of Quantitative Science, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeh","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Division of Quantitative Science, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine"},{"name":"Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barrett Craig","family":"Lawson","sequence":"additional","affiliation":[{"name":"Department of Pathology, MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Kolin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Herman","family":"Chui","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Vang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tricia A.","family":"Numan","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Rinda","family":"Soong","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brant G.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Inova Fairfax Hospital"},{"name":"University of Virginia School of Medicine Inova Campus, Falls Church, VA"},{"name":"Department of Pathology, Georgetown University Medical Center, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saron Ann","family":"Smith","sequence":"additional","affiliation":[{"name":"Legacy Health Systems, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Long","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Taipei Medical University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Stone","sequence":"additional","affiliation":[{"name":"Departments of Gynecology and Obstetrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Douville","sequence":"additional","affiliation":[{"name":"Department of Oncology, Division of Quantitative Science, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Gynecology and Obstetrics"},{"name":"Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ie-Ming","family":"Shih","sequence":"additional","affiliation":[{"name":"Departments of Gynecology and Obstetrics"},{"name":"Department of Biostatistics, 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