Abstract
Objective
To evaluate human epidermal growth factor receptor 2 (HER2) status in endometrial carcinoma (EC) using 3 different criteria, assess its association with clinicopathological and molecular characteristics, and investigate intertumoral heterogeneity and prognostic significance, focusing on HER2-low.
Methods
HER2 immunohistochemistry was performed on whole-slide sections from 365 EC and interpreted using EC, gastric cancer (GC), and breast cancer (BC) criteria. Silver in situ hybridization was performed for 2+/3+ cases. Intertumoral heterogeneity was assessed in 30 matched primary and recurrent/metastatic tumors.
Results
Among 365 ECs, HER2-positive tumors (2.0%) were strongly associated with serous histology, high-grade, and the p53-abnormal (p53-abn) subgroup (p<0.001). HER2-low (45.7% by EC criteria and 18% by GC/BC criteria) was associated with advanced stage (p=0.045) and high-grade tumors (p=0.009), respectively. HER2-expression was enriched in p53-abn (60.4%, 37.7%), high-/advanced-risk (56.2%, 60.0%), and International Federation of Gynecology and Obstetrics III–IV (60.0%, 62.5%) tumors. Intertumoral heterogeneity was substantial (40.0%, 30.0%), reflecting dynamic changes, particularly in serous histology (p=0.018) and high-grade tumors (p=0.034). Based on GC/BC criteria, HER2-low status was an independent prognostic factor for recurrence in high- and advanced-risk groups compared with HER2-0 (p=0.040).
Conclusion
HER2 status in EC varies across scoring criteria, supporting the need for standardized interpretation. HER2 expression, including HER2-low, was more prevalent in biologically aggressive subsets, and HER-low showed prognostic relevance in high-/advanced-risk patients, supporting its potential value as a therapeutic target for antibody-drug conjugate therapy. The dynamic nature of HER2 across disease progression further supports the need for reassessment in recurrent or metastatic lesions.
Keywords: Genes, erbB-2; Biomarkers, Tumor; Endometrial Carcinoma; Immunohistochemistry; Prognosis
Synopsis
Human epidermal growth factor receptor 2 (HER2) status in endometrial carcinoma (EC) was evaluated using 3 diagnostic criteria. HER2 expression was associated with aggressive features, and enriched in high-risk EC with poor prognosis. Dynamic HER2 changes in recurrent/metastatic disease underscore the need for reassessment.
INTRODUCTION
Endometrial carcinoma (EC) is a heterogeneous malignancy with a rising incidence and mortality in developed countries [1]. Although most patients are diagnosed at an early stage and have a favorable prognosis, a subset with high-grade histology or advanced-stage disease experiences poor clinical outcomes. The recent incorporation of molecular classification into clinical practice has enhanced risk stratification, with the p53-mutant subgroup consistently associated with aggressive behavior and poor survival [2]. Despite this, therapeutic options for these patients remain limited, relying primarily on conventional chemotherapy. This therapeutic gap, combined with the increasing incidence, underscores the urgent need for novel treatment strategies [3].
Human epidermal growth factor receptor 2 (HER2) has emerged as a potential therapeutic target in EC, particularly in the serous and p53-abnormal (p53-abn) subtypes, where HER2 overexpression or amplification is relatively common [4,5]. Clinical trials have demonstrated that HER2-targeted agents, including trastuzumab and antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd), can improve outcomes in HER2-positive and HER2-low ECs [6,7,8]. Numerous recent studies have focused not only on HER2-positive tumors but also on HER2-low tumors, aiming to characterize their clinicopathologic and molecular features to refine patient selection for HER2-targeted therapies [9,10].
Considering the limited treatment options for EC and the clinical effect of HER2-targeted therapy, there is considerable clinical interest in expanding HER2-targeted therapy to other subtypes of EC. Moreover, there were no standardized guidelines for assessing HER2 status in EC. Therefore, we evaluated HER2 status in all subtypes of EC using 3 different criteria and investigated its association with clinicopathological and molecular characteristics. Moreover, we evaluated intertumoral heterogeneity by comparing matched primary and recurrent/metastatic tumors and the prognostic significance of HER2 status.
MATERIALS AND METHODS
1. Case selection
This retrospective study was conducted at Seoul National University Bundang Hospital and approved by the Institutional Review Board (approval number: B-2008-628-304). We reviewed the medical records and pathological reports of 365 patients with primary EC who underwent surgery between May 2006 and December 2018. Among these, 30 patients had matched primary and recurrent or metastatic tumor samples available for HER2 concordance analysis.
Clinicopathologic variables collected included age at diagnosis, histologic subtype, depth of myometrial invasion, lymphovascular space invasion (LVSI), International Federation of Gynecology and Obstetrics (FIGO) grade and stage, European Society for Medical Oncology-European Society of Gynaecological Oncology-European Society for Radiotherapy & Oncology risk classification, and receipt of adjuvant therapy. Two pathologists (H.Y. and H.K.) independently reviewed hematoxylin and eosin-stained slides to confirm the diagnosis based on the 2020 WHO classification system [11]. Tumors with endometrioid, serous, clear-cell, or mixed histology were included. Patients who received neoadjuvant therapy were excluded.
2. Molecular classification
Molecular classification was performed using surrogate markers to stratify cases into the 4 TCGA-like subtypes [2,12,13]. Immunohistochemistry (IHC) was performed using a tissue microarray (TMA) to assess mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, PMS2) and p53 expression. To minimize sampling bias from intratumoral heterogeneity (ITH), paired 2-mm cores were extracted from representative tumor areas of each block and arranged into new TMAs using a trephine apparatus (SuperBioChips Laboratories, Seoul, Korea). Details on molecular marker evaluation (POLE, MMR, p53) are summarized in Table S1. For tumors with more than one molecular feature, hierarchical classification was applied: POLE-mutated > MMR-deficient > p53-abn, as previously described [14,15].
3. HER2 evaluation
HER2 IHC was performed on whole-tissue sections of both primary and recurrent/metastatic tumors to address ITH. A rabbit monoclonal anti-HER2/neu antibody (clone 4B5; Ventana Medical Systems, Tucson, AZ, USA) was used. HER2 expression was assessed by 2 pathologists using 3 distinct scoring criteria: endometrial, gastric, and breast cancer guidelines [16,17,18]. Discrepant cases were resolved by consensus review. ITH of HER2 expression was defined by having at least a 2-degree change in the intensity of HER2 expression (none to moderate, weak to strong, or none to strong) involving at least 5% of the tumor [19].
HER2 amplification was assessed by silver in situ hybridization (SISH) in cases with IHC scores of 2+ or 3+ (Fig. S1A and B), using the VENTANA HER2 Dual ISH DNA Probe Cocktail assay (Roche Diagnostics, Indianapolis, IN, USA). HER2 (black) and CEP17 (red) signals were counted in ≥20 tumor cell nuclei. Amplification was defined as a HER2/CEP17 ratio ≥2.0, or a ratio <2.0 with an average HER2 copy number ≥6 per cell [16]. HER2 status was classified as follows [20]:
• HER2-positive: IHC 3+ or IHC 2+ with SISH-positive
• HER2-low: IHC 1+ or IHC 2+ with SISH-negative
• HER2-zero: IHC 0
4. Statistical analysis
Categorical variables were summarized using frequencies and percentages, while continuous variables were described using medians and ranges. Group comparisons were conducted using the χ2 test or Fisher’s exact test for categorical variables, and the independent t test for continuous variables. Concordance between scoring systems and between paired primary and metastatic tumors was evaluated using Cohen’s kappa coefficient (κ). Survival curves of progression-free survival (PFS) and overall survival (OS) were performed using the Kaplan–Meier method and compared using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards regression model. Two-sided p-values <0.05 were considered statistically significant. Analyses were performed using IBM SPSS Statistics (version 25.0; IBM Corp., Armonk, NY, USA).
RESULTS
1. HER2 expression and HER2 status according to different scoring criteria
HER2 IHC was performed in all cases. By EC criteria, 191 (52.3%) were 0, 150 (41.1%) 1+, 20 (5.5%) 2+, and 4 (1.1%) 3+. Gastric cancer (GC) criteria classified 292 (80.0%) as 0, 49 (13.4%) 1+, 18 (4.9%) 2+, and 6 (1.6%) 3+. According to breast cancer (BC) criteria, 292 (80.0%) were 0, 56 (15.3%) 1+, 12 (3.3%) 2+, and 5 (1.4%) 3+ (Fig. 1A). The concordance rate between EC and GC criteria was 71.78% (κ=0.461), which was slightly higher than that between EC and BC criteria (70.14%, κ=0.422).
Fig. 1. Proportions of HER2 expression and HER2 status. (A) HER2 expression based on different criteria, (B) HER2 status based on EC criteria, (C) HER2 status based on GC criteria, and (D) HER2 status based on BC criteria.
BC, breast cancer; EC, endometrial cancer; GC, gastric cancer; HER2, human epidermal growth factor receptor 2.
SISH was performed in 24 cases with IHC scores of 2+ or 3+. All cases of IHC 3+ were amplified by SISH, but only 3 out of 20 IHC 2+ cases were amplified. ITH was identified in 17 out of 20 IHC 2+ cases and in all IHC 3+ cases. Notably, ITH on IHC correlated with genetic heterogeneity detected by SISH. (Fig. S1C-E).
Therefore, according to EC criteria, 7 cases (2%) were HER2-positive, 167 (45.7%) HER2-low, and 191 (52.3%) HER2-0 (Fig. 1B). Since the cases categorized as HER2-positive, HER2-low, and HER2-0 are concordant under the GC and BC criteria, they are collectively described hereafter, with proportions of 2%, 18%, and 80%, respectively (Fig. 1C and D).
2. Histologic subtype distribution of HER2 expression and amplification
Among the cases with IHC 3+ based on EC criteria, 3 were serous carcinoma, and one was endometrioid carcinoma. IHC 2+ was most frequently observed in endometrioid carcinoma (n=12), followed by mixed endometrioid-serous (E+S) carcinoma (n=5), serous carcinoma (n=2), and mixed endometrioid-clear cell (E+C) carcinoma (n=1). Of the 5 IHC 2+ mixed E+S carcinomas, 4 showed HER2 2+ expression in the serous component, whereas one in the endometrioid component. For the IHC 2+ mixed E+C carcinoma, HER2 2+ was expressed in the clear cell component. When applying GC scoring criteria, of the 6 IHC 3+ cases, 4 were serous carcinoma, and 1 case each was endometrioid and mixed E+S carcinoma. Among the 18 IHC 2+, 12 were endometrioid, 4 were mixed (E+S) carcinoma, and 1 case each was serous and mixed E+C carcinoma. According to BC criteria, among the 5 IHC 3+, 4 were serous, and 1 was endometrioid. Of the 12 IHC 2+ cases, 9 were endometrioid, 2 were mixed E+S carcinoma, and 1 was serous carcinoma (Table S2).
HER2 amplification was observed in 5/18 (27.8%) of serous carcinoma, 1/6 (16.7%) of mixed E+S carcinoma, and 1/333 (0.3%) of endometrioid carcinoma. In mixed E+S carcinoma, amplification was observed in the serous component. HER2 was not amplified in clear cell carcinoma (Table S2).
3. Clinicopathological characteristics
Tables S3, S4, S5 shows the comparison of clinicopathological characteristics among HER2-0, HER2-low, and HER2-positive EC. Based on EC criteria, the HER2-positive group was significantly associated with older age (p<0.001 and p=0.003), serous histology (p<0.001), high-grade (p<0.001), p53-abn subgroup (p<0.001 and p=0.001), and high-risk group (p=0.001 and p=0.004) compared to HER2-0 and HER2-low tumors. No significant differences were observed between HER2 categories for myometrial invasion, LVSI, or adjuvant treatment. Based on GC and BC criteria, HER2-positive was significantly associated with older age (p=0.003 and p=0.006), serous histology (p<0.001), high grade (p<0.001), p53-abn subgroup (p<0.001 and p=0.006) and high-risk group (p=0.001 and p=0.011) compared to HER2-0 and HER2-low, consistent with findings using EC criteria.
According to EC criteria, the HER2-low group was associated with advanced FIGO 2023 stage compared to the HER2-0 group (p=0.045). Based on GC and BC criteria, the proportion of high-grade tumors was significantly higher in the HER2-low group compared to the HER2-0 group (p=0.009) (Tables S3, S4, S5).
Furthermore, HER2-positive and HER2-low tumors were classified as HER2-expressing tumors, which are potentially responsive to ADCs, and compared with HER2-0 tumors. According to the EC criteria, HER2-expressing tumors were most frequently observed in the p53-abn group (60.4%), high- (56.2%) or advanced-risk (60.0%) groups, and in FIGO stage III (60.0%) or IV (62.5%) (Fig. S2A-C). Similarly, under the GC and BC criteria, HER2-expressing tumors were enriched in the p53-abn group (37.7%), high- (27.4%) or advanced-risk (40.0%) groups, and in FIGO stage IV (37.5%) (Fig. S2D-I).
4. Discordance of HER2 status between primary and matched recurrent/metastatic tumors
HER2 testing was performed in 30 patients with paired primary and recurrent/metastatic lesions. Using EC criteria, the discordance between primary and matched recurrent/metastatic tumors was 40.0%, with a Cohen’s kappa coefficient of 0.226, reflecting poor agreement. Notably, 6 showed a downward shift, while 6 showed an upward shift (Fig. 2A). Similarly, with GC and BC criteria, discordance was 30.0% (κ=0.082), with 5 downward and 4 upward shifts (Fig. 2B and C).
Fig. 2. Evolution of HER2 status from primary to recurrent/metastatic tumors in patients with EC. HER2 status evaluated by (A) EC, (B) gastric cancer, and (C) breast cancer criteria.
EC, endometrial cancer; HER2, human epidermal growth factor receptor 2.
The clinicopathologic characteristics of the 30 patients are summarized in Table S6. Based on EC criteria, serous carcinoma was exclusively found in the discordant group (p=0.018), and high-grade tumors were more likely to exhibit HER2 discordance (p=0.034). No clinicopathologic features were significantly associated with HER2 concordance when using GC or BC criteria.
5. Survival analysis
We performed survival analyses according to HER2 status in the entire cohort. The Kaplan-Meier curve analysis showed that HER2 status was not statistically significant for PFS according to the 3 criteria (EC criteria: p=0.368, GC/BC criteria: p=0.267) (Fig. 3A-C). However, for OS, it was demonstrated that the HER2-positive group had significantly worse prognosis compared to both the HER2-0 and HER2-low groups (EC criteria: p = 0.002, GC/BC criteria: p<0.001) (Fig. 3D-F). In the multivariate analysis adjusted for age, histologic subtype, 2023 FIGO stage, and HER2 status, age (p=0.042) and FIGO stage (p<0.001) were significant independent prognostic factors for PFS across all criteria, whereas only FIGO stage was independently prognostic for OS (p=0.025 based on EC criteria, p=0.032 based on GC/BC criteria (Table 1).
Fig. 3. Survival analyses. (A-F) Kaplan–Meier survival analyses stratified by HER2 status in the overall cohort (A-F) and in high- and advanced-risk patients (G-L) using endometrial cancer (A, D, G, J), gastric cancer (B, E, H, K), and breast cancer (C, F, I, L) criteria. (A-C, G-I) PFS, (D-F, J-L) OS.
HER2, human epidermal growth factor receptor 2; OS, overall survival; PFS, progression-free survival.
*Statistically significant.
Table 1. Multivariate survival analysis in the entire cohort according to HER2 status.
| Clinicopathologic characteristics | PFS | OS | ||||
|---|---|---|---|---|---|---|
| HR (95% CI) | p-value | HR (95% CI) | p-value | |||
| Endometrial cancer criteria | ||||||
| Age | 1.031 (1.001–1.061) | 0.042* | 1.048 (0.994–1.105) | 0.083 | ||
| Histologic subtype | ||||||
| Serous vs. non-serous | 0.889 (0.316–2.496) | 0.823 | 0.375 (0.083–1.693) | 0.202 | ||
| FIGO stage (2023) | ||||||
| III–IV vs. I–II | 6.366 (3.533–11.471) | <0.001* | 3.485 (1.171–10.371) | 0.025* | ||
| HER2 status | ||||||
| HER2-low vs. HER2-0 | 0.919 (0.516–1.635) | 0.773 | 0.925 (0.317–2.701) | 0.887 | ||
| HER2-positive vs. HER2-0 | 0.896 (0.166–4.850) | 0.899 | 1.848 (0.250–13.674) | 0.547 | ||
| Gastric cancer criteria | ||||||
| Age | 1.031 (1.001–1.061) | 0.042* | 1.048 (0.995–1.105) | 0.079 | ||
| Histologic subtype | ||||||
| Serous vs. non-serous | 0.933 (0.331–2.626) | 0.895 | 0.415 (0.091–1.901) | 0.257 | ||
| FIGO stage (2023) | ||||||
| III–IV vs. I–II | 6.261 (3.486–11.243) | <0.001* | 3.322 (1.109–9.953) | 0.032* | ||
| HER2 status | ||||||
| HER2-low vs. HER2-0 | 1.224 (0.620–2.416) | 0.560 | 2.212 (0.734–6.667) | 0.159 | ||
| HER2-positive vs. HER2-0 | 1.022 (0.195–5.362) | 0.979 | 2.620 (0.377–18.193) | 0.330 | ||
| Breast cancer criteria | ||||||
| Age | 1.031 (1.001–1.061) | 0.042* | 1.048 (0.995–1.105) | 0.079 | ||
| Histologic subtype | ||||||
| Serous vs. non-serous | 0.933 (0.331–2.626) | 0.895 | 0.415 (0.091–1.901) | 0.257 | ||
| FIGO stage (2023) | ||||||
| III–IV vs. I–II | 6.261 (3.486–11.243) | <0.001* | 3.322 (1.109–9.953) | 0.032* | ||
| HER2 status | ||||||
| HER2-low vs. HER2-0 | 1.224 (0.620–2.416) | 0.560 | 2.212 (0.734–6.667) | 0.159 | ||
| HER2-positive vs. HER2-0 | 1.022 (0.195–5.362) | 0.979 | 2.620 (0.377–18.193) | 0.330 | ||
CI, confidence interval; FIGO, International Federation of Gynecology and Obstetrics; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; OS, overall survival; PFS, progression-free survival.
*Statistically significant.
To further assess the prognostic relevance of the HER2-low subgroup within the high- and advanced-risk groups, Kaplan–Meier survival analysis was performed. Based on GC and BC criteria, the HER2-low group showed significantly worse outcomes than the HER2-0 group for both PFS (p=0.036) (Fig. 3H and I) and OS (p=0.045) (Fig. 3K and L). In contrast, HER2 status evaluated by EC criteria did not demonstrate statistical significance (Fig. 3G and J). In the multivariate analysis adjusted for age, histologic subtype, and HER2 status, HER2-low status was identified as an independent prognostic factor for PFS (p=0.040), but not for OS (p=0.069) (Table 2).
Table 2. Multivariate survival analysis in the high- and advanced-risk group according to HER2 status.
| Clinicopathologic characteristics | PFS | OS | ||||
|---|---|---|---|---|---|---|
| HR (95% CI) | p-value | HR (95% CI) | p-value | |||
| Endometrial cancer criteria | ||||||
| Age | 1.014 (0.980–1.050) | 0.429 | 0.983 (0.927–1.043) | 0.571 | ||
| Histologic subtype | ||||||
| Serous vs. non-serous | 1.191 (0.455–3.118) | 0.721 | 0.402 (0.103–1.570) | 0.190 | ||
| HER2 status | ||||||
| HER2-low vs. HER2-0 | 1.705 (0.849–3.422) | 0.134 | 1.583 (0.461–5.438) | 0.465 | ||
| Gastric cancer criteria | ||||||
| Age | 1.013 (0.979–1.048) | 0.465 | 0.983 (0.926–1.043) | 0.566 | ||
| Histologic subtype | ||||||
| Serous vs. non-serous | 1.234 (0.471–3.235) | 0.668 | 0.432 (0.110–1.693) | 0.228 | ||
| HER2 status | ||||||
| HER2-low vs. HER2-0 | 2.148 (1.034–4.462) | 0.040* | 3.033 (0.918–10.028) | 0.069 | ||
| Breast cancer criteria | ||||||
| Age | 1.013 (0.979–1.048) | 0.465 | 0.983 (0.926–1.043) | 0.566 | ||
| Histologic subtype | ||||||
| Serous vs. non-serous | 1.234 (0.471–3.235) | 0.668 | 0.432 (0.110–1.693) | 0.228 | ||
| HER2 status | ||||||
| HER2-low vs. HER2-0 | 2.148 (1.034–4.462) | 0.040* | 3.033 (0.918–10.028) | 0.069 | ||
CI, confidence interval; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; OS, overall survival; PFS, progression-free survival.
*Statistically significant.
DISCUSSION
In this study, we evaluated HER2 status in EC using 3 scoring criteria with specific focus on the emerging HER2-low category, and we demonstrated substantial discordance in HER2 status between paired primary and recurrent/metastatic tumors. These findings highlight the dynamic nature of HER2 expression in EC and the need for careful reassessment in the metastatic setting.
HER2 amplification was observed in 27.8% of uterine serous carcinomas, consistent with previous reports [21,22]. Recent evidence suggests that HER2 overexpression correlates more strongly with p53-abn tumors than with histologic subtype alone [4,23,24]. In line with these observations, our cohort included one endometrioid carcinoma with p53 mutation showing HER2 overexpression. These results underscore the importance of HER2 testing beyond histologic type and support incorporating HER2 assessment into the diagnostic workup of p53-abn EC to identify candidates for HER2-directed therapies.
Comparison of 3 scoring systems (EC, GC, and BC criteria) revealed clinically relevant differences. EC criteria classified a greater proportion as HER2-low, likely due to more inclusive IHC 1+ thresholds. GC criteria exhibited higher sensitivity for identifying truly HER2-positive tumors, as all GC 3+ cases corresponded to SISH amplification. In addition, GC criteria consider basolateral/lateral membranous staining, which is more consistent with staining patterns observed in EC [21,25]. Notably, one basolateral/lateral case in our study was SISH-positive, suggesting that GC criteria may better reflect HER2 biology in EC than BC criteria.
HER2 positivity was significantly associated with serous histology, high grade, and the p53-abn subtype, in agreement with previous studies [4,24]. Although the clinical significance of HER2-low tumors remains under discussion, HER2-low status showed associations with higher FIGO grade or stage depending on the scoring criteria, indicating that HER2-low may also reflect biologically aggressive disease. Furthermore, HER2-expressing tumors (HER2-positive and HER2-low) were enriched in aggressive subsets, particularly within p53-abn, advanced-stage, and high-/advanced-risk groups, suggesting that these patients may represent a relevant target population for ADCs.
A key finding of our study is the high rate of discordance in HER2 status between primary and metastatic ECs, with low concordance across all 3 scoring criteria. Similar patterns have been reported in breast and GCs, where HER2 evolution influences treatment eligibility and resistance [26,27,28]. In EC, HER2 discordance was associated with serous histology and high grade, suggesting that biologically aggressive tumors may be particularly prone to HER2 shifts. These findings support repeat HER2 testing in the metastatic setting, especially when considering ADCs such as T-DXd, which may benefit even HER2-low tumors.
Although HER2-positive tumors were associated with worse OS in univariate analysis, this association did not persist in multivariate models. HER2-low status did not demonstrate prognostic significance in the full cohort; however, in high- and advanced-risk groups, HER2-low tumors defined by GC/BC criteria were associated with significantly poorer PFS and remained an independent prognostic factor. These results suggest that the prognostic relevance of HER2-low may be confined to biologically aggressive EC subsets and that GC/BC criteria may better capture prognostic differences than EC criteria.
This study has limitations, including a relatively small sample size and a retrospective design from a single institution. Nevertheless, strengths include whole-slide assessment to evaluate ITH, integration of the HER2-low category across molecular subtype and 2023 FIGO stage, and paired analysis of primary and metastatic lesions.
In conclusion, HER2 status in EC varies substantially according to scoring criteria, emphasizing the need for standardized interpretation. HER2 expression, including HER2-low, evolves dynamically between primary and metastatic tumors, highlighting the clinical value of reassessment in recurrent/metastatic disease. HER2-expressing tumors were enriched in aggressive EC subsets, and HER2-low was an independent prognostic factor for recurrence in high- and advanced-risk groups. These findings provide support for incorporating HER2 re-evaluation into clinical management and may inform future selection of patients for HER2-directed ADC therapies.
Footnotes
Funding: Supported by grant from the Seoul National University College of Medicine Research Foundation (Next-Generation Research Grant in the Department of Pathology).
Conflict of Interest: No potential conflict of interest relevant to this article was reported.
Data Availability: All relevant data are included in the report and associated files.
- Conceptualization: Y.H., K.H.
- Data curation: Y.H., H.Y.B., S.D.H., K.K., N.J.H., K.Y.B., K.H.
- Formal analysis: Y.H., K.H.
- Investigation: Y.H., K.H.
- Methodology: Y.H., K.H.
- Supervision: Y.H., K.H.
- Validation: Y.H., K.H.
- Visualization: Y.H., K.H.
- Writing - original draft: Y.H., K.H.
- Writing - review & editing: Y.H., K.H.
SUPPLEMENTARY MATERIALS
POLE, MMR and p53 evaluation
Histologic subtype distribution of human epidermal growth factor receptor 2 expression and amplification according to different scoring criteria
Clinicopathological characteristics based on endometrial cancer criteria according to HER2 status
Clinicopathological characteristics based on gastric cancer criteria according to HER2 status
Clinicopathological characteristics based on breast cancer criteria according to HER2 status
Associations between HER2 status concordance and clinicopathologic characteristics
Representative slides of HER2 expression. (A) IHC 3+, (B) IHC 2+, (C) Intratumoral heterogeneity in HER2 expression, (D) HER2 amplified area, and (E) HER2 non-amplified area.
Distribution of HER2 status according to three different criteria. HER2 status based on endometrial cancer (A-C), gastric cancer (D-F), breast cancer criteria (G-I) criteria. The proportions of HER2-expressing tumors in each molecular group (A, D, G), in each ESMO-ESGO-ESTRO risk group (B, E, H), and in each 2023 FIGO stage (C, F, I). The percentage shown on the top indicates the proportion of HER2-0 tumors, whereas the percentage displayed at the bottom represents the proportion of HER2-expressing tumors (HER2-positive and HER2-low).
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Associated Data
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Supplementary Materials
POLE, MMR and p53 evaluation
Histologic subtype distribution of human epidermal growth factor receptor 2 expression and amplification according to different scoring criteria
Clinicopathological characteristics based on endometrial cancer criteria according to HER2 status
Clinicopathological characteristics based on gastric cancer criteria according to HER2 status
Clinicopathological characteristics based on breast cancer criteria according to HER2 status
Associations between HER2 status concordance and clinicopathologic characteristics
Representative slides of HER2 expression. (A) IHC 3+, (B) IHC 2+, (C) Intratumoral heterogeneity in HER2 expression, (D) HER2 amplified area, and (E) HER2 non-amplified area.
Distribution of HER2 status according to three different criteria. HER2 status based on endometrial cancer (A-C), gastric cancer (D-F), breast cancer criteria (G-I) criteria. The proportions of HER2-expressing tumors in each molecular group (A, D, G), in each ESMO-ESGO-ESTRO risk group (B, E, H), and in each 2023 FIGO stage (C, F, I). The percentage shown on the top indicates the proportion of HER2-0 tumors, whereas the percentage displayed at the bottom represents the proportion of HER2-expressing tumors (HER2-positive and HER2-low).