Ali Ben-Mussa, Rajeev Shah, Simon Rajendran, W Glenn McCluggage
{"title":"A Population-based Study Investigating the Incidence of Human Papillomavirus-Associated and Human Papillomavirus-Independent Cervical Adenocarcinomas.","authors":"Ali Ben-Mussa, Rajeev Shah, Simon Rajendran, W Glenn McCluggage","doi":"10.1097/PGP.0000000000001063","DOIUrl":"10.1097/PGP.0000000000001063","url":null,"abstract":"<p><p>Cervical adenocarcinomas are now classified as human papillomavirus (HPV)-associated and HPV-independent types with the former being more common. However, population-based studies regarding the relative incidences of the 2 types are few. This study investigates the incidence of cervical adenocarcinomas in Northern Ireland (a country with a relatively stable population of ~1.8 million) over a recent 9-year period (2015-2023). Overall, there were 146 primary cervical adenocarcinomas, 130 HPV-associated (89%) and 16 HPV-independent (11%). The median age was 43 years (range: 24-82) for HPV-associated and 62.5 years (range: 31-84) for HPV-independent neoplasms; this was statistically significant ( P < 0.001). The calculated age-adjusted incidence of the patients with HPV-associated and HPV-independent neoplasms was 1.68 and 0.20 per 100,000 person-years, respectively. The HPV-independent neoplasms were more often advanced stage at diagnosis; 97 of 130 (75.4%) of the HPV-associated cases were diagnosed at Stage I compared with 5 of 16 (31.3%) of the HPV-independent cases. The HPV-independent neoplasms were mostly gastric-type (56.3%) with smaller numbers of clear cells and mesonephric. Despite the relatively short follow-up, the mortality of patients with HPV-independent adenocarcinomas was significantly higher than patients with HPV-associated neoplasms (56.3% vs 5.4%) with a median survival of just over a year (13.2 mo) in the former for those who died.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"249-254"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cem Yagmur Ozdemir, Dagistan Tolga Arioz, Mine Kanat Pektaş, Cigdem Ozdemir, Nayif Cicekli, Filiz Bilir, Riza Dur, Ecenur Goztepe
{"title":"How Can \"No Specific Molecular Profile\" Heterogeneity be Reduced in Molecularly Classified Endometrial Cancer?: Prognostic Significance of L1 Cell Adhesion Molecule.","authors":"Cem Yagmur Ozdemir, Dagistan Tolga Arioz, Mine Kanat Pektaş, Cigdem Ozdemir, Nayif Cicekli, Filiz Bilir, Riza Dur, Ecenur Goztepe","doi":"10.1097/PGP.0000000000001057","DOIUrl":"10.1097/PGP.0000000000001057","url":null,"abstract":"<p><p>This study aims to investigate the role of L1 cell adhesion molecule (L1CAM) in the prognostic assessment of endometrial cancers that have been depicted as having no specific molecular profile (NSMP) in molecular classification. This is a retrospective review of 150 patients who received the diagnosis of endometrial cancer and underwent surgery at the study center between January 2008 and January 2022. When evaluating L1CAM immunohistochemical staining, scoring was done according to the percentage of positivity in tumor cells. Accordingly, score 0 = 0%, score 1=1% to 10%, score 2 = >10% to 50% and score 3 = >50%. If the staining in tumor cells was ≥10% (scores 2 and 3), it was considered positive. The patients with L1CAM positivity had significantly more frequent lymphovascular space invasion and lymph node metastasis than patients with L1CAM negativity ( P = 0.013 and P = 0.007). L1CAM expression was strongly associated with mutant p53 ( P = 0.003). Recurrence was significantly higher ( P = 0.001) and overall survival and progression-free survival were significantly lower in patients with L1CAM positivity ( P = 0.001 for both). Seventy-nine patients (52.7%) were put into NSMP group. About 84.8% of them (n = 67) were L1CAM negative and 15.2% of them (n = 12) were L1CAM-positive. Recurrence was significantly higher ( P = 0.001) and overall survival and progression-free survival were significantly lower in patients with NSMP who were positive for L1CAM ( P = 0.002 and P = 0.001, respectively). This study demonstrates that L1CAM expression status may add prognostic information to endometrial cancer, particularly in the NSMP subgroup. Considering the prognostic importance of L1CAM, its use as a marker may make significant contributions to reducing prognostic heterogeneity, especially in the NSMP subgroup.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"230-236"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinicopathologic and Genomic Features of Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix Coexisting With High-grade Squamous Intraepithelial Lesion.","authors":"Xinyuan Long, Xiaoting Ma, Wei Xiao, Jinghuan Lv","doi":"10.1097/PGP.0000000000001075","DOIUrl":"10.1097/PGP.0000000000001075","url":null,"abstract":"<p><p>Invasive stratified mucin-producing carcinoma (ISMC) is a specific type of adenocarcinoma of the cervix, which is associated with human papillomavirus infection and often coexists with other types of carcinomas. However, given its rarity, understanding of this disease remains insufficient. We present a unique case of ISMC of the cervix coexisting with a high-grade squamous intraepithelial lesion (HSIL). In addition to histologic and immunohistochemical feature observation, genomic profiling of the 2 lesions was performed. Histologically, the ISMC and HSIL lesions were independent of each other. Aside from the typical morphology, various architectural features of ISMC were observed. Immunohistochemically, the ISMC and HSIL lesions were strongly and diffusely positive for p16 and exhibited high Ki-67 expression. The ISMC lesion was also positive for CK7, MUC5AC, and MUC6, while it was negative for PAX-8. The HSIL lesion was positive for CK5/6 and p40. The combined positive score of PD-L1 was 55. The other markers were all negative in both lesions, and the p53 was wild-type. Next-generation sequencing analysis revealed multiple gene mutations in the ISMC and HSIL lesions. A total of 88 gene mutations were identified in the ISMC lesion, while 20 gene mutations were identified in the HSIL lesion. Three mutations ( ERBB2 , histidine decarboxylase gene [ HDC ], and BSN ) were detected in the ISMC and HSIL lesions. Both lesions had a low tumor mutation burden and microsatellite-stable status. No copy number-associated variants or structural variations were identified in either lesion. These results suggest that patients with ISMC may benefit from PD-L1 immunotherapy and targeted therapy.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"268-273"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David K Carlson, Cheyenne Painter, Sarah E Gradecki, Kari L Ring, Eli S Williams, Anne M Mills
{"title":"High-grade Endometrial Carcinomas With Solid Basaloid Morphology and Geographic Necrosis Lacking Definitive Pilomatrix-like Features: Clinicopathologic Characteristics Including Aggressive Behavior and Novel Molecular Events.","authors":"David K Carlson, Cheyenne Painter, Sarah E Gradecki, Kari L Ring, Eli S Williams, Anne M Mills","doi":"10.1097/PGP.0000000000001081","DOIUrl":"10.1097/PGP.0000000000001081","url":null,"abstract":"<p><p>High-grade endometrioid carcinomas occasionally demonstrate solid basaloid morphology with geographic necrosis (SB-GN). This pattern is among the defining features of pilomatrix-like high-grade endometrioid carcinoma (PiMHEC), a recently proposed tumor type which is additionally characterized by the presence of shadow cells, abnormal beta-catenin/ CTNNB1 mutations, strong CDX2 expression, and poor outcomes. Clinicopathologic overlap between PiMHEC and other high-grade endometrial cancers with SB-GN has not been established. We screened 300 endometrial carcinomas on tissue microarray for SB-GN histology and performed a detailed whole-section morphologic review, immunohistochemical analysis, and next-generation sequencing on all cases bearing this pattern. Four (1.3%) demonstrated SB-GN. All 3 with clinical follow-up had extremely aggressive behavior despite being MMR-deficient; in contrast, only 27% of other MMR-deficient high-grade carcinomas recurred. One SB-GN case met most of the previously outlined diagnostic criteria for PiMHEC including abnormal beta-catenin/ CTNNB1 (p.S37P variant) and strong CDX2 expression; notably, however, shadow cells were absent. This case also demonstrated a KRAS p.A59T pathogenic variant. The other 3 cases also lacked shadow cells; the 2 with sequencing data bore no CTNNB1 abnormalities but showed likely oncogenic variants involving the pilomatrixoma-associated gene FGFR2. All 3 cases with molecular results also bore somatic Notch pathway ( NOTCH1/NOTCH2/NOTCH3 ) variants. The single case treated with immunotherapy showed complete and sustained response with regression of bone metastases despite abnormal beta-catenin/ CTNNB1 , which has been associated with immunotherapeutic resistance. These data suggest that the SB-GN pattern may connote a poor prognosis even in the absence of overt pilomatrix-like differentiation, and that novel molecular events may have implications for the treatment of these tumors.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"199-209"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kelly Wei, Noorah Almadani, Emina Torlakovic, Ryan Haupt, Lyndal Anderson, Richard Crawford, Gustavo Focchi, Blake Gilks, Lars-Christian Horn, Mayada Kellow, Yen Chen Kevin Ko, Jaume Ordi, Carlos Parra-Herran, Naveena Singh, Stephanie Skala, Sarah Strickland, Jaclyn Watkins, Richard Wong, Janine Senz, Derek Chiu, Lynn Hoang, Marilyn Kinloch
{"title":"Proficiency Testing of p53 Immunohistochemistry Pattern Read-out in Vulvar Biopsies Demonstrates Frequent Basal Overexpression Interpretation in TP53 Wild-type Cases.","authors":"Kelly Wei, Noorah Almadani, Emina Torlakovic, Ryan Haupt, Lyndal Anderson, Richard Crawford, Gustavo Focchi, Blake Gilks, Lars-Christian Horn, Mayada Kellow, Yen Chen Kevin Ko, Jaume Ordi, Carlos Parra-Herran, Naveena Singh, Stephanie Skala, Sarah Strickland, Jaclyn Watkins, Richard Wong, Janine Senz, Derek Chiu, Lynn Hoang, Marilyn Kinloch","doi":"10.1097/PGP.0000000000001111","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001111","url":null,"abstract":"<p><p>Recently, criteria for p53 immunohistochemistry (IHC) interpretation were described in squamous neoplasia of the vulva. This pattern-based approach detailed 2 wild-type patterns (scattered and basal-sparing) and 4 mutant patterns (parabasal/diffuse overexpression, basal overexpression, null, and cytoplasmic). However, the proficiency of pathologist read-out has not been studied. We created an online tool to evaluate p53 IHC interpretation proficiency. p53 IHC on 90 vulvar biopsies (n=31 squamous insitu/premalignant and n=59 benign lesions) were scanned (without corresponding H&E). Fifteen pathologists assessed 45 cases in Module A and assigned each case as wild-type or mutant via the 6 p53 IHC patterns. Following Module A, participants were given the suggested p53 IHC pattern and TP53 sequencing data for each case. After self-review, pathologists completed a second 45 case set (Module B). The average pathologist score per case increased from Module A to Module B (69.8%-87.7%, P=0.0005). Pathologist proficiency was excellent in the parabasal/diffuse (100%-100%), null (93.3%-90.0%), and basal-sparing (88.9%-100%) patterns. The greatest discrepancy was due to the interpretation of the basal overexpression pattern in cases that were TP53 wild-type by sequencing, but this improved with educational intervention. Scores for the scattered pattern improved from 64.9% to 82.8% and basal overexpression from 73.3% to 91.1% after completion of the training module. Pathologists should exhibit caution when interpreting p53 IHC as basal overexpression, as this pattern can be seen in the absence of TP53 alterations. There were 2 cases with convincing p53 IHC abnormal patterns (1 parabasal/diffuse and 1 null) without TP53 mutations by sequencing.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annamari Leino, Anton Nostolahti, Anne Ahtikoski, Jutta Huvila
{"title":"Molecular Subtype and Mutational Profile of Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia.","authors":"Annamari Leino, Anton Nostolahti, Anne Ahtikoski, Jutta Huvila","doi":"10.1097/PGP.0000000000001113","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001113","url":null,"abstract":"<p><p>Endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN) is the acknowledged precursor of most endometrial carcinomas. Our aim was to assess the molecular alterations and the 4 specific molecular subtypes in EAH/EIN diagnosed on endometrial biopsy. Forty EAH/EIN biopsies were stained for estrogen receptor (ER), mismatch repair (MMR) proteins (PMS2 and MSH6), and p53 and were subjected to genomic testing (NGS Panel, Canexia Health V5). Based on these results, cases were assigned to 1 of 4 molecular subtypes [POLEmut, MMRd, p53abn, and no specific molecular profile (NSMP)]. Follow-up data was collected. There was 1 POLEmut case with a pathogenic POLE mutation (P286R), 5 were MMRd, 1 was p53abn, and the remaining 33 were NSMP. Thirty-nine of 40 cases harbored one or several mutations known to be associated with endometrial carcinoma pathogenesis (PIK3CA, PTEN, and CTNNB1). On follow-up, there was carcinoma or EAH identified in a subsequent hysterectomy or biopsy in 6 of 6 patients with MMRd or p53abn EAH, compared with 19 of 34 with NSMP or POLEmut (P=0.067). Most EAH/EIN (33/40, 81.5%) are of the NSMP molecular subtype. Molecular subtypes other than NSMP (eg, POLE mutation, MMR deficiency, and p53 mutant pattern staining) are present in EAH/EIN but are less common than in carcinoma. Mutations associated with EC pathogenesis were identified in 39/40 (97.5%) biopsies containing EAH/EIN, highlighting the neoplastic nature of this lesion and raising the possibility of using sequencing (NGS) as an adjuvant test to support a diagnosis of EAH/EIN.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nooshin K Dashti, Amy A Swanson, Gary L Keeney, Mark A Edgar, Sounak Gupta, John Kenneth Schoolmeester
{"title":"Alterations of G-protein Activating Subunit Genes in Ovarian Hemangiomas: A Molecular Study of 6 Cases Including 3 Anastomosing Hemangiomas With a Cavernous Component.","authors":"Nooshin K Dashti, Amy A Swanson, Gary L Keeney, Mark A Edgar, Sounak Gupta, John Kenneth Schoolmeester","doi":"10.1097/PGP.0000000000001107","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001107","url":null,"abstract":"","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anjali Walia, Nicholas R Ladwig, Julie S Mak, Joseph T Rabban
{"title":"Prevalence of Occult Ovarian Cancer and Metastatic Breast Cancer in Ovarian Ablation Specimens of Patients With Hormone Receptor-Positive Breast Cancer: Implications for Tissue Sampling Strategies, Early Ovarian Cancer Detection and Resource Utilization.","authors":"Anjali Walia, Nicholas R Ladwig, Julie S Mak, Joseph T Rabban","doi":"10.1097/PGP.0000000000001055","DOIUrl":"10.1097/PGP.0000000000001055","url":null,"abstract":"<p><p>Bilateral oophorectomy is one method of hormone suppression for premenopausal patients with hormone receptor-positive breast cancer. Such specimens could, in theory, harbor occult early ovarian cancer and/or metastatic breast cancer but guidelines for tissue sampling for pathologic examination remain to be addressed. Therefore, we evaluated oophorectomy specimens from 166 patients who underwent ovarian ablation for hormone receptor-positive breast cancer. Results of germline genetic testing were documented by the surgeon in only 31.3% of the pathology specimen requisition forms, whereas that information was available for 81.3% of patients elsewhere in the electronic medical records. All but 5.2% tested negative for a hereditary ovarian cancer gene pathogenic variant before oophorectomy. Complete tissue sampling was performed in 77.1% of the cases and representative sampling in the remainder. No cases of ovarian cancer were observed. Ovarian metastasis of breast cancer was identified in 9.6% of patients, all of whom were already known to have advanced-stage disease. The number of tissue cassettes per ovary required for complete tissue submission was on average three times higher than that for representative tissue sampling ( P < 0.01) and ranged up to 20 cassettes per ovary when multiple follicle cysts were present. We propose that guidelines for tissue sampling in this context be defined by a combination of hereditary risk and macroscopic examination; representative sampling is reasonable for macroscopically normal ovaries in hormone receptor-positive breast cancer patients whose germline genetic testing is negative. Positive genetic test results merit complete tissue submission even if macroscopically normal. This strategy balances the goals of early ovarian cancer detection and optimal resource utilization. However, it depends on clear documentation of genetic test results. Our study demonstrates that many opportunities remain to close gaps in the communication of genetic test results by clinicians submitting oophorectomy specimens for pathologic evaluation.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"174-181"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lars Velthof, Jo Van Dorpe, Philippe Tummers, David Creytens, Koen Van de Vijver
{"title":"TRPS1 Is Consistently Expressed in Hidradenoma Papilliferum.","authors":"Lars Velthof, Jo Van Dorpe, Philippe Tummers, David Creytens, Koen Van de Vijver","doi":"10.1097/PGP.0000000000001042","DOIUrl":"10.1097/PGP.0000000000001042","url":null,"abstract":"<p><p>TRPS1 is a novel immunohistochemical marker, so far quite specific and sensitive for breast cancer and especially useful for the diagnosis of triple-negative breast cancer. TRPS1 expression has recently been reported in normal skin appendages, as well as in a variety of benign and malignant cutaneous tumors, including adnexal tumors. However, it has not yet been reported in hidradenoma papilliferum (papillary hidradenoma), a benign adnexal neoplasm, accepted to originate from mammary-like glands in the vulvar or anogenital region of middle-aged women. We report consistent nuclear expression of TRPS1 in the epithelium of 9/9 cases of hidradenoma papilliferum, while in 2/2 cases with foci of oxyphilic metaplasia, these foci were consistently negative for TRPS1 immunohistochemistry. Our findings are in line with the theory that hidradenoma papilliferum is derived from mammary-like glands and showed that TRPS1 can be an additional sensitive immunohistochemical marker for hidradenoma papilliferum.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"99-103"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Barrett C Lawson, Mario L Marques-Piubelli, Shannon N Westin, Anais Malpica
{"title":"Folate Receptor Immunohistochemical Staining and Gynecologic Tumors: Initial Experience With 216 Cases.","authors":"Barrett C Lawson, Mario L Marques-Piubelli, Shannon N Westin, Anais Malpica","doi":"10.1097/PGP.0000000000001053","DOIUrl":"10.1097/PGP.0000000000001053","url":null,"abstract":"<p><p>Folate receptor alpha has been shown to have possible mechanisms of tumorigenesis in malignancies, becoming a potential target for therapy. Mirvetuximab soravtansine is an antifolate receptor alpha monoclonal antibody, with an approved FOLR1-2.1 immunohistochemical biomarker. After IRB approval, a retrospective review of gynecologic pathology cases was performed to identify cases in which FOLR1 immunohistochemistry (IHC) was performed at our institution over a period of 9 months as part of clinical care for therapy eligibility. Clinical data collected included patients' age, tumor histotype, tumor grade, primary tumor site, FIGO stage, dates of recurrence/progression, and use of mirvetuximab therapy. FOLR1 IHC data were recorded, including the date specimen obtained, date IHC was performed, site tested, case type, percentage tumor staining, and intensity. Cases were deemed positive or negative according to current recommendations (75%, 2-3+intensity). Two hundred sixteen cases were identified. Patient ages ranged from 25 to 83 years old (median: 59 yr). Staining intensity was reported as 0 in 15 (6.9%) cases, weak (1+) in 8 (3.7%), moderate (2+) in 27 (12.5%), strong (3+) in 27 (12.5%), weak-to-moderate (1-2+) in 15 (6.9%), and moderate-to-strong (2-3+) in 99 (45.8%); intensity was not provided in 25 (11.6%). Percentage of tumor staining ranged from 0 to 100, with a median of 60. The IHC was overall deemed positive in 98 (45.4%) cases and negative in 118 (54.6%). By histotype, 5 of 17 (29.4%) low-grade serous carcinomas, 88 of 162 (54.3%) high-grade serous carcinomas, 3 of 5 (60%) of carcinosarcomas, and 2 of 6 (33.3%) of mixed carcinomas were positive. No case of clear cell CA, endometrioid CA, Mullerian CA NOS, serous borderline, mucinous CA, or granulosa cell tumor was positive. The primary site of disease was tubo-ovarian in 192 (88.9%) cases, peritoneal in 8 (3.7%) cases, uterine in 3 (1.4%) cases, and unknown in 13 (6%) cases. By site on which immunohistochemical stain was performed: primary site positive in 53 of 96 (55.2%) cases, metastatic site at time of diagnosis/debulking positive in 23 of 41 (52.1%) cases, and metastatic/recurrent cases positive in 22 of 79 (27.8%) cases. There was a statistically significant correlation when comparing the positivity rates between these sites ( P = 0.0004). Survival data were examined with high-grade serous carcinoma, with no statistically significant difference between positive and negative cases in overall survival ( P = 0.622) or progression-free survival ( P = 0.711). Biopsy specimens were positive in 17 (25%) cases, while negative in 51 (75%), whereas resection specimens were positive in 81 (54.7%) and negative in 67 (45.3%), a statistically significant difference ( P < 0.0001). Cases that were <19 months old had 38 (36.2%) positive and 67 (63.8%) negative, compared with cases ≥19 months old that had 60 (54.1%) positive and 51 (45.9%) negative, a statistically significant difference ( P = ","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"167-173"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}