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9. Clinical Behavior and Molecular Landscape of Stage I p53-abnormal Low-Grade Endometrioid Endometrial Carcinomas

Author

Jamieson, Amy, primary, Vermij, Lisa, additional, Kramer, Claire J.H., additional, Jobsen, Jan J., additional, Jürgenliemk-Schulz, Ina, additional, Lutgens, Ludy, additional, Mens, Jan Willem, additional, Haverkort, Marie A.D., additional, Slot, Annerie, additional, Nout, Remi A., additional, Oosting, Jan, additional, Carlson, Joseph, additional, Howitt, Brooke E., additional, Ip, Philip P.C., additional, Lax, Sigurd F., additional, McCluggage, W. Glenn, additional, Singh, Naveena, additional, McAlpine, Jessica N., additional, Creutzberg, Carien L., additional, Horeweg, Nanda, additional, Gilks, C. Blake, additional, and Bosse, Tjalling, additional

Published
2023
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12. Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas

Author

Jamieson, Amy, Vermij, Lisa, Kramer, Claire J.H., Jobsen, Jan J., Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A.D., Slot, Annerie, Nout, Remi A., Oosting, Jan, Carlson, Joseph, Howitt, Brooke E., Ip, Philip P.C., Lax, Sigurd F., McCluggage, W. Glenn, Singh, Naveena, McAlpine, Jessica N., Creutzberg, Carien L., Horeweg, Nanda, Gilks, C. Blake, Bosse, Tjalling, Jamieson, Amy, Vermij, Lisa, Kramer, Claire J.H., Jobsen, Jan J., Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A.D., Slot, Annerie, Nout, Remi A., Oosting, Jan, Carlson, Joseph, Howitt, Brooke E., Ip, Philip P.C., Lax, Sigurd F., McCluggage, W. Glenn, Singh, Naveena, McAlpine, Jessica N., Creutzberg, Carien L., Horeweg, Nanda, Gilks, C. Blake, and Bosse, Tjalling

Abstract

PURPOSE: The clinical significance of the p53-abnormal (p53abn) molecular subtype in stage I low-grade endometrioid endometrial carcinoma (EEC) is debated. We aimed to review pathologic and molecular characteristics, and outcomes of stage I low-grade p53abn EEC in a large international cohort. EXPERIMENTAL DESIGN: Previously diagnosed stage I p53abn EC (POLE-wild-type, mismatch repair-proficient) low-grade EEC from Canadian retrospective cohorts and PORTEC-1&2 trials were included. Pathology review was performed by six expert gynecologic pathologists blinded to p53 status. IHC profiling, next-generation sequencing, and shallow whole-genome sequencing was performed. Kaplan-Meier method was used for survival analysis. RESULTS: We identified 55 stage I p53abn low-grade EEC among 3,387 cases (2.5%). On pathology review, 17 cases (31%) were not diagnosed as low-grade EEC by any pathologists, whereas 26 cases (47%) were diagnosed as low-grade EEC by at least three pathologists. The IHC and molecular profile of the latter cases were consistent with low-grade EEC morphology (ER/PR positivity, patchy p16 expression, PIK3CA and PTEN mutations) but they also showed features of p53abn EC (TP53 mutations, many copy-number alterations). These cases had a clinically relevant risk of disease recurrence (5-year recurrence-free survival 77%), with pelvic and/or distant recurrences observed in 12% of the patients. CONCLUSIONS:A subset of p53abn EC is morphologically low-grade EEC and exhibit genomic instability. Even for stage I disease, p53abn low-grade EEC are at substantial risk of disease recurrence. These findings highlight the clinical relevance of universal p53-testing, even in low-grade EEC, to identify women at increased risk of recurrence.

Published
2023

13. Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas

Author

MS Radiotherapie, Cancer, Jamieson, Amy, Vermij, Lisa, Kramer, Claire J H, Jobsen, Jan J, Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A D, Slot, Annerie, Nout, Remi A, Oosting, Jan, Carlson, Joseph, Howitt, Brooke E, Ip, Philip P C, Lax, Sigurd F, McCluggage, W Glenn, Singh, Naveena, McAlpine, Jessica N, Creutzberg, Carien L, Horeweg, Nanda, Gilks, C Blake, Bosse, Tjalling, MS Radiotherapie, Cancer, Jamieson, Amy, Vermij, Lisa, Kramer, Claire J H, Jobsen, Jan J, Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A D, Slot, Annerie, Nout, Remi A, Oosting, Jan, Carlson, Joseph, Howitt, Brooke E, Ip, Philip P C, Lax, Sigurd F, McCluggage, W Glenn, Singh, Naveena, McAlpine, Jessica N, Creutzberg, Carien L, Horeweg, Nanda, Gilks, C Blake, and Bosse, Tjalling

Published
2023

19. Detection rates and factors affecting thereof in endometrial hyperplasia, endometrial carcinoma, and cervical glandular lesions on cervical smear.

Author

Ng, Joanna K. M., Cheung, Bryan H. C., Lee, Dennis H. Y., Li, Joshua J. X., Ip, Philip P. C., Lee, Jacqueline H. S., Yeung, Carol S. Y., and Yu, Mei‐Yung

Subjects
ENDOMETRIAL hyperplasia, ENDOMETRIAL cancer, CYTODIAGNOSIS, GENITALIA, CARCINOMA, DIAGNOSIS
Abstract

Introduction: Endometrial lesions are morphologically diverse and uncommon on cervical smears, with its detection rate and associated diagnostic categories uncharacterized. In this study, cervical smears matched to histologically proven endometrial hyperplasias and carcinomas were reviewed and compared with cervical in‐situ‐carcinomas/carcinomas, aiming to detail the diagnostic performance of cervical smears for upper tract and glandular lesions. Methods: Pathology reports of cervical smears, hysterectomies, endometrial and cervical biopsies from 1995 to 2021 were retrieved. Diagnoses of cervical smears were matched to endometrial hyperplasias and carcinomas, or cervical carcinomas and reviewed. Results: Totally 832 cervical smears (272 cervical carcinomas, 312 endometrial carcinomas, and 248 hyperplasias) were included. Considering all cytologic glandular diagnosis as positive, the detection rate of cervical adenocarcinoma‐in‐situ was the highest (64.3%), followed by cervical adenocarcinoma (63.8%), endometrial carcinoma (31.7%), and hyperplasia (with atypia–8.5%; without atypia–2.3%) (p < 0.001). Endometrial hyperplasia was most often diagnosed as atypical squamous cells of undetermined significance (ASCUS) (5.0%) or atypical glandular cells, not otherwise specified (3.6%) without indication of endometrial origin. For endometrial carcinomas, higher FIGO grading and endocervical involvement were associated with higher detection rates across all diagnostic categories (p = 0.002–0.028). High FIGO grade was associated with suspicious/favor neoplastic (C4) (31.1%vs10.3%, p < 0.001) and carcinoma (C5) (17.8% vs. 5.6%, p = 0.005) categories, but not for all glandular diagnoses combined (33.3% vs. 31.0%, p = 0.761). Conclusion: Detection rates for endometrial lesions are lower than cervical lesions but not insignificant. Endometrial hyperplasia should be recognized as a differential of human papilloma virus‐negative ASCUS and prompt consideration of investigation of the upper genital tract. [ABSTRACT FROM AUTHOR]

Published
2023
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28. Development of a Multi-Institutional Prediction Model for Three-Year Survival Status in Patients with Uterine Leiomyosarcoma (AGOG11-022/QCGC1302 Study)

Author

Tse, Ka-Yu, primary, Wong, Richard Wing-Cheuk, additional, Chao, Angel, additional, Ueng, Shir-Hwa, additional, Yang, Lan-Yan, additional, Cummings, Margaret, additional, Smith, Deborah, additional, Lai, Chiung-Ru, additional, Lau, Hei-Yu, additional, Yen, Ming-Shyen, additional, Cheung, Annie Nga-Yin, additional, Leung, Charlotte Ka-Lun, additional, Chan, Kit-Sheung, additional, Chan, Alice Ngot-Htain, additional, Li, Wai-Hon, additional, Choi, Carmen Ka-Man, additional, Pong, Wai-Mei, additional, Hui, Hoi-Fong, additional, Yuk, Judy Ying-Wah, additional, Yao, Hung, additional, Yuen, Nancy Wah-Fun, additional, Obermair, Andreas, additional, Lai, Chyong-Huey, additional, Ip, Philip Pun-Ching, additional, and Ngan, Hextan Yuen-Sheung, additional

Published
2021
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36. A Selective β−Catenin‐Metadherin/CEACAM1‐CCL3 Axis Mediates Metastatic Heterogeneity upon Tumor–Macrophage Interaction.

Author

To, Sally K. Y., Tang, Maggie K. S., Tong, Yin, Zhang, Jiangwen, Chan, Karen K. L., Ip, Philip P. C., Shi, Jue, and Wong, Alice S. T.

Subjects
CANCER relapse, METASTASIS, CATENINS, HETEROGENEITY, CANCER cells, OVARIAN cancer
Abstract

Tumor heterogeneity plays a key role in cancer relapse and metastasis, however, the distinct cellular behaviors and kinetics of interactions among different cancer cell subclones and the tumor microenvironment are poorly understood. By profiling an isogenic model that resembles spontaneous human ovarian cancer metastasis with an highly metastatic (HM) and non‐metastatic (NM) tumor cell pair, one finds an upregulation of Wnt/β‐catenin signaling uniquely in HM. Using humanized immunocompetent mice, one shows for the first time that activated β‐catenin acts nonautonomously to modulate the immune microenvironment by enhancing infiltrating tumor‐associated macrophages (TAM) at the metastatic site. Single‐cell time‐lapse microscopy further reveals that upon contact with macrophages, a significant subset of HM, but not NM, becomes polyploid, a phenotype pivotal for tumor aggressiveness and therapy resistance. Moreover, HM, but not NM, polarizes macrophages to a TAM phenotype. Mechanistically, β‐catenin upregulates cancer cell surface metadherin, which communicates through CEACAM1 expressed on macrophages to produce CCL3. Tumor xenografts in humanized mice and clinical patient samples both corroborate the relevance of enhanced metastasis, TAM activation, and polyploidy in vivo. The results thus suggest that targeting the β‐catenin‐metadherin/CEACAM1‐CCL3 positive feedback cascade holds great therapeutic potential to disrupt polyploidization of the cancer subclones that drive metastasis. [ABSTRACT FROM AUTHOR]

Published
2022
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38. International Society of Gynecological Pathologists (ISGyP) Endometrial Cancer Project : Guidelines From the Special Techniques and Ancillary Studies Group:Guidelines From the Special Techniques and Ancillary Studies Group

Author

Cho, Kathleen R, Cooper, Kumarasen, Croce, Sabrina, Djordevic, Bojana, Herrington, C Simon, Howitt, Brooke, Hui, Pei, Ip, Philip, Koebel, Martin, Lax, Sigurd, Quade, Bradley J, Shaw, Patricia, Vidal, August, Yemelyanova, Anna, Clarke, Blaise, Hedrick Ellenson, Lora, Longacre, Teri A, Shih, Ie-Ming, McCluggage, W Glenn, Malpica, Anais, Oliva, Esther, Parkash, Vinita, and Matias-Guiu, Xavier

Abstract

The aim of this article is to propose guidelines and recommendations in problematic areas in pathologic reporting of endometrial carcinoma (EC) regarding special techniques and ancillary studies. An organizing committee designed a comprehensive survey with different questions related to pathologic features, diagnosis, and prognosis of EC that was sent to all members of the International Society of Gynecological Pathologists. The special techniques/ancillary studies group received 4 different questions to be addressed. Five members of the group reviewed the literature and came up with recommendations and an accompanying text which were discussed and agreed upon by all members of the group. Twelve different recommendations are made. They address the value of immunohistochemistry, ploidy, and molecular analysis for assessing prognosis in EC, the value of steroid hormone receptor analysis to predict response to hormone therapy, and parameters regarding applying immunohistochemistry and molecular tests for assessing mismatch deficiency in EC.

Published
2019
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40. Oncogenic microRNA signature for early diagnosis of cervical intraepithelial neoplasia and cancer

Author

Liu, Stephanie S., primary, Chan, Karen K. L., additional, Chu, Daniel K. H., additional, Wei, Tina N., additional, Lau, Lesley S. K., additional, Ngu, Siew F., additional, Chu, Mandy M. Y., additional, Tse, Ka Yu, additional, Ip, Philip P. C., additional, Ng, Enders K. O., additional, Cheung, Annie N. Y., additional, and Ngan, Hextan Y. S., additional

Published
2018
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42. Su1031 High Liver Stiffness Measurement by Transient Elastography Predicts High Grade Post-Hepatectomy Liver Failure in Patients With Hepatocellular Carcinoma: A Prospective Cohort Study

Author

Chong, Charing, primary, Wong, Grace, additional, Wong, Vincent W., additional, Ip, Philip, additional, Fong, KWONG WAI Anthony, additional, Cheung, Sunny, additional, Wong, John, additional, Lee, Kit-fai, additional, Lai, Paul B., additional, and Chan, Henry L., additional

Published
2015
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