HER2-low and Overexpression in Mucinous Ovarian Cancer: Analysis of ASCO/CAP and ToGA Immunohistochemical Scoring.
Journal
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
ISSN: 1538-7151
Titre abrégé: Int J Gynecol Pathol
Pays: United States
ID NLM: 8214845
Informations de publication
Date de publication:
04 Mar 2024
04 Mar 2024
Historique:
medline:
4
3
2024
pubmed:
4
3
2024
entrez:
4
3
2024
Statut:
aheadofprint
Résumé
Mucinous ovarian carcinoma is an uncommon malignancy characterized by resistance to chemotherapy and poor survival in the metastatic setting. HER2 amplification is a frequent late event in carcinogenesis, yet the incidence of HER2-low in mucinous ovarian carcinoma is unknown. Further, the optimal method for determining overexpression in these tumors is not established. We sought to assess the ASCO/CAP and ToGA trial scoring methods for HER2 IHC with correlation to FISH, p53, and mismatch repair protein status and to determine the incidence of HER2-low in mucinous ovarian carcinoma. A total of 29 tumors from 23 patients were included. Immunohistochemistry for HER2, p53, MLH1, PMS2, MSH2, and MSH6 was performed. Scoring was performed according to the ASCO/CAP and ToGA trial criteria. HER2 FISH was performed and scored according to the ASCO/CAP criteria. The proportion of HER2-low, defined as 1+ or 2+ staining with negative FISH, was determined. Using ASCO/CAP, 26% demonstrated 3+ while 35% demonstrated 2+ staining. Using ToGA, 30% demonstrated 3+ while 57% demonstrated 2+ staining. By FISH, 26% were positive for HER2 amplification. Both systems captured all FISH-positive cases; the use of ASCO/CAP resulted in fewer equivocal and false-positive cases. Among HER2-negative cases, 88% were HER2-low. Aberrant p53 expression was detected in 55% of cases; mismatch repair deficiency was not identified in any cases. ASCO/CAP guidelines are accurate and resource-effective in determining HER2 overexpression in mucinous ovarian carcinoma. HER2-low is common in these tumors; further studies to determine the role of HER2-targeted therapy including antibody-drug conjugates are indicated.
Identifiants
pubmed: 38436360
doi: 10.1097/PGP.0000000000000972
pii: 00004347-990000000-00151
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 by the International Society of Gynecological Pathologists.
Déclaration de conflit d'intérêts
A.M. declares honoraria from AstraZeneca, Clovis, GSK, and PharmaMar. S.L. declares consulting fees from AstraZeneca, GSK, Roche, Merck, Eisai, Novocure, and Shattuck Labs. S.L. is the principal investigator or co-investigator of different clinical trials with agents from AstraZeneca, Merck, Roche, GSK, Regeneron, Repare Therapeutics, and Clovis. A.C.S. declares honoraria from Pfizer and personal financial interest in Bionano Genomics. The remaining authors declare no conflict of interest.
Références
Köbel M, Kalloger SE, Huntsman DG, et al. Differences in tumor type in low-stage versus high-stage ovarian carcinomas. Int J Gynecol Pathol 2010;29:203–11.
Morice P, Gouy S, Leary A. Mucinous ovarian carcinoma. N Engl J Med 2019;380:1256–66.
Schiavone MB, Herzog TJ, Lewin SN, et al. Natural history and outcome of mucinous carcinoma of the ovary. Am J Obstet Gynecol 2011;205:480.e1–8.
Mueller JJ, Lajer H, Mosgaard BJ, et al. International study of primary mucinous ovarian carcinomas managed at tertiary medical centers. Int J Gynecol Cancer 2018;28:915–24.
Zaino RJ, Brady MF, Lele SM, et al. Advanced stage mucinous adenocarcinoma of the ovary is both rare and highly lethal: a Gynecologic Oncology Group study. Cancer 2011;117:554–62.
Ménard S, Pupa SM, Campiglio M, et al. Biologic and therapeutic role of HER2 in cancer. Oncogene 2003;22:6570–8.
Iqbal N, Iqbal N. Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Mol Biol Int 2014;2014:852748.
Cheasley D, Wakefield MJ, Ryland GL, et al. The molecular origin and taxonomy of mucinous ovarian carcinoma. Nat Commun 2019;10:3935.
Gorringe KL, Cheasley D, Wakefield MJ, et al. Therapeutic options for mucinous ovarian carcinoma. Gynecol Oncol 2020;156:552–60.
Wolff AC, Hammond MEH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol 2018;36:2105–22.
Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376:687–97.
Buza N, English DP, Santin AD, et al. Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice. Mod Pathol 2013;26:1605–12.
Koopman T, van der Vegt B, Dijkstra M, et al. HER2 immunohistochemistry in endometrial and ovarian clear cell carcinoma: discordance between antibodies and with in-situ hybridisation. Histopathology 2018;73:852–63.
Rechsteiner M, Zimmermann AK, Wild PJ, et al. TP53 mutations are common in all subtypes of epithelial ovarian cancer and occur concomitantly with KRAS mutations in the mucinous type. Exp Mol Pathol 2013;95:235–41.
Zhang H, Katerji H, Turner BM, et al. HER2-low breast cancers. Am J Clin Pathol 2022;157:328–36.
Chao WR, Lee MY, Lin WL, et al. Assessing the HER2 status in mucinous epithelial ovarian cancer on the basis of the 2013 ASCO/CAP guideline update. Am J Surg Pathol 2014;38:1227–34.
Kao KR, Hasan T, Baptista A, et al. Effect of fixation time on breast biomarker expression: a controlled study using cell line-derived xenografted (CDX) tumours. J Clin Pathol 2017;70:832–7.
Chao WR, Lee MY, Ruan A, et al. Assessment of HER2 status using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) techniques in mucinous epithelial ovarian cancer: a comprehensive comparison between ToGA biopsy method and ToGA surgical specimen method. PLoS One 2015;10:e0142135.
Buza N. HER2 testing and reporting in endometrial serous carcinoma: practical recommendations for HER2 immunohistochemistry and fluorescent in situ hybridization: proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual Meeting. Int J Gynecol Pathol 2021;40:17–23.
Kim SK, Cho NH. HER2-positive mucinous adenocarcinomas of the ovary have an expansile invasive pattern associated with a favorable prognosis. Int J Clin Exp Pathol 2014;7:4222–30.
Mackenzie R, Kommoss S, Winterhoff BJ, et al. Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms. BMC Cancer 2015;15:415.
Anglesio MS, Kommoss S, Tolcher MC, et al. Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas. J Pathol 2013;229:111–20.
Chay WY, Chew SH, Ong WS, et al. HER2 amplification and clinicopathological characteristics in a large Asian cohort of rare mucinous ovarian cancer. PLoS One 2013;8:e61565.
McAlpine JN, Wiegand KC, Vang R, et al. HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy. BMC Cancer 2009;9:433.
Siddiqui AZ, Almhanna K. Beyond chemotherapy, PD-1, and HER-2: novel targets for gastric and esophageal cancer. Cancers (Basel) 2021;13:4322.
Fader AN, Roque DM, Siegel E, et al. Randomized phase II trial of carboplatin-paclitaxel compared with carboplatin-paclitaxel-trastuzumab in advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress Her2/Neu (NCT01367002): updated overall survival analysis. Clin Cancer Res 2020;26:3928–35.
Madariaga A, Oza AM. Wee1 inhibition in recurrent serous uterine cancer: science paving the way in a challenging disease. J Clin Oncol 2021;39:1513–7.
Jain A, Ryan PD, Seiden MV. Metastatic mucinous ovarian cancer and treatment decisions based on histology and molecular markers rather than the primary location. J Natl Compr Canc Netw 2012;10:1076–80.
Tarantino P, Carmagnani Pestana R, Corti C, et al. Antibody-drug conjugates: smart chemotherapy delivery across tumor histologies. CA Cancer J Clin 2022;72:165–82.
Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 2022;387:9–20.
Chui MH, Ryan P, Radigan J, et al. The histomorphology of Lynch syndrome-associated ovarian carcinomas: toward a subtype-specific screening strategy. Am J Surg Pathol 2014;38:1173–81.
Rambau PF, Duggan MA, Ghatage P, et al. Significant frequency of MSH2/MSH6 abnormality in ovarian endometrioid carcinoma supports histotype-specific Lynch syndrome screening in ovarian carcinomas. Histopathology 2016;69:288–97.