Abstract 790P
Background
HER2 is a transmembrane tyrosine kinase receptor, mediating cell proliferation and apoptosis inhibition. In breast and gastric tumors, HER2 -overexpression (HER2-OE) assessed by immunohistochemistry (IHC) is a validated prognostic and predictive biomarker with well-established scoring guidelines. However, its significance in GTs remains unclear, lacking no specific guidelines.
Methods
To establish prevalence of HER2-OE in GTs, archival formalin-fixed, paraffin-embedded tumor blocks from patients diagnosed at our academic institution were analyzed during 2023-2024. Tumor samples were stained using a validated HER2 monoplex-IHC panel (anti-HER2/neu 4B5 Rabbit monoclonal antibody) using Ventana system. HER2-OE was firstly scored using Breast Cancer ASCO-CAP (BCG) and subsequently ASCO-CAP-ASCP Gastroesophageal Adenocarcinoma (GEG) Guidelines. Concordance rates (CR) between both methods were calculated. HER2-OE scores were correlated with tumor molecular profiles.
Results
A total of 324 GTs were evaluated including 194 epithelial ovarian (OC), 80 endometrial (EC) and 31 cervical cancers (CC). Percentage of HER2-OE scores by BGC: 0, +1, +2, and +3 were 58%, 29%, 11% and 2%, respectively in all GTs. In OC: 56%, 30%, 12% and 2%. In EC: 51%, 34%, 13% and 2%. And, in CC: 65%, 19%, 9.7% and 6.3%. Percentage of HER2-OE scores by GEG: 0, +1, +2, +3 were 56%, 28%, 14% and 2%, respectively in all GTs. In OC: 55%, 29%, 14%, and 2%. In EC: 51%, 30%, 15% and 4%. And in CC, 55%, 26%, 13%, and 6%. Overall CR between BCG and GEG was 89.78%. CR in OC, EC an CC was: 92.78%, 85% and 80.65%, respectively. HER2-OE according to tumor molecular features are shown in the table. Table: 790P
| BCG | GEG | |||||||
| 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | |
| OC HRD status N (%) | ||||||||
| HRD positive | 28 (61) | 13 (28) | 5(11) | 0 (0) | 27 (59) | 11 (24) | 8 (17) | 0 (0) |
| HRD negative | 17 (45) | 15 (39) | 5(13) | 1 (3) | 16 (42) | 15 (39) | 6 (16) | 1 (3) |
| Molecular profile EC N (%) | ||||||||
| MMRd | 14 (52) | 9 (33) | 4(15) | 0 (0) | 13 (48) | 9 (33) | 4 (15) | 1 (4) |
| p53 abnormal | 16 (47) | 11 (32) | 6(18) | 1 (3) | 17 (50) | 8 (24) | 8 (24) | 1 (2) |
| NSMP | 11 (58) | 7 (37) | 0 (0) | 1 (5) | 11 (50) | 8 (24) | 0 (0) | 1 (6) |
| Histology CC N (%) | ||||||||
| Squamous | 12 (71) | 3 (18) | 2(12) | 0 (0) | 10 (55) | 5 (29) | 2 (15) | 0 (0) |
| adenocarcinoma | 6 (60) | 1 (10) | 1(10) | 2 (20) | 4 (40) | 2 (20) | 2 (20) | 2 (20) |
| CPS CC N (%) | ||||||||
CPSConclusionsHER2-OE was relatively low across GTs, though certain histotypes and molecular features (HRD negative OCs, p53 abnormal EC and adenocarcinomas/CPS<1% CC) exhibited higher scores. The high CR suggests either scoring guideline may be suitable for GTs. HER2-OE's predictive/prognostic value in GTs requires further evaluation. Clinical trial identificationEditorial acknowledgementLegal entity responsible for the studyVall d’Hebron Institute of Oncology. FundingHas not received any funding. DisclosureC. Garcia Duran: Financial Interests, Institutional, Invited Speaker: MSD-AstraZeneca, GSK; Financial Interests, Institutional, Other, Educative activity: EISAI; Financial Interests, Personal, Other, Travel expenses: GSK, AstraZeneca. J.F. Grau Béjar: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK; Financial Interests, Personal, Other, Educational Activities: AstraZeneca; Financial Interests, Personal, Other, Travel Expenses: GSK. D.G. Illescas: Financial Interests, Personal, Other, Travel expenses: GSK, MSD-AstraZeneca; Financial Interests, Personal, Invited Speaker: GSK. L. Fariñas Madrid: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Institutional, Invited Speaker: AstraZeneca & MSD, Pharma&; Financial Interests, Personal, Invited Speaker: Eisai, GSK. G. Villacampa: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabre, GSK; Financial Interests, Personal, Invited Speaker, Internal discussion about the interpretation of some published results: Pfizer; Financial Interests, Personal, Other, Collaborations with specific projects: Reveal Genomics. A. Oaknin: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, F. Hoffmann-La Roche, GSK, Genmab, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Novocure, OncoXerna Therapeutics, Inc, PharmaMar, Regeneron, Shattuck Labs, Seagen/Pfizer, Sutro Biopharma, Exelisis, Daiichi Sankyo, Debiopharm International, Myriad Genetics, Zentalis; Financial Interests, Personal, Other, Travel and accommodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Amgen, AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Aprea Therapeutics AB, Regeneron Pharmaceuticals, Clovis Oncology Inc, Eisai limited LTD, F. Hoffmann –La Roche LTD, ImmunoGen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines: ESMO; Non-Financial Interests, Leadership Role, ESMO GYN Co-Chair 2023 - 2025: ESMO; Non-Financial Interests, Leadership Role, Chair de Cervix Committee. 2022-2024: GCIG; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. All other authors have declared no conflicts of interest. 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