TY - JOUR
T1 - HER2 Status in High-Risk Endometrial Cancers (PORTEC-3): Relationship with Histotype, Molecular Classification, and Clinical Outcomes
AU - Vermij, Lisa
AU - Horeweg, Nanda
AU - Leon-castillo, Alicia
AU - Rutten, Tessa A.
AU - Mileshkin, Linda R.
AU - Mackay, Helen J.
AU - Leary, Alexandra
AU - Powell, Melanie E.
AU - Singh, Naveena
AU - Crosbie, Emma J.
AU - Smit, Vincent T.h.b.m.
AU - Creutzberg, Carien L.
AU - Bosse, Tjalling
PY - 2020/12/25
Y1 - 2020/12/25
N2 - HER2-status has not been investigated in the context of the molecular endometrial cancer (EC) classification. Here, we aimed to determine the clinicopathological features and prognostic significance of HER2-status in the molecularly classified PORTEC-3 trial population of patients with high-risk EC (HREC). HER2-testing was performed on tumour-tissues of 407 molecularly classified HREC. HER2-status was determined by HER2 immunohistochemistry (IHC; all cases) and subsequent HER2 dual in situ hybridization for cases with any (in)complete moderate to strong membranous HER2-IHC expression. Χ2 test and Spearman Rho correlation coefficient were used to compare clinicopathological and molecular features. The Kaplan-Meier method, log-rank test and Cox proportional-hazard models were used for survival analysis. We identified 24 (5.9%) HER2-positive EC of various histological subtypes including serous (n=9, 37.5%), endometrioid (n=6, 25.0%) and clear cell (n=5, 20.8%). HER2-positivity was highly associated with the p53-abnormal subgroup (p53abn, 23/24 cases; p<0.0001). The correlation between p53abn and HER2-status (ρ=0.438 p<0.0001) was significantly stronger (p<0.0001) than between serous histology and HER2-status (ρ=0.154; p=0.002). HER2-status did not have independent prognostic value for survival after correction for the molecular classification. Our study strongly suggests that molecular subclass-directed HER2-testing is superior to histotype-directed testing. This insight will be relevant for future trials targeting HER2.
AB - HER2-status has not been investigated in the context of the molecular endometrial cancer (EC) classification. Here, we aimed to determine the clinicopathological features and prognostic significance of HER2-status in the molecularly classified PORTEC-3 trial population of patients with high-risk EC (HREC). HER2-testing was performed on tumour-tissues of 407 molecularly classified HREC. HER2-status was determined by HER2 immunohistochemistry (IHC; all cases) and subsequent HER2 dual in situ hybridization for cases with any (in)complete moderate to strong membranous HER2-IHC expression. Χ2 test and Spearman Rho correlation coefficient were used to compare clinicopathological and molecular features. The Kaplan-Meier method, log-rank test and Cox proportional-hazard models were used for survival analysis. We identified 24 (5.9%) HER2-positive EC of various histological subtypes including serous (n=9, 37.5%), endometrioid (n=6, 25.0%) and clear cell (n=5, 20.8%). HER2-positivity was highly associated with the p53-abnormal subgroup (p53abn, 23/24 cases; p<0.0001). The correlation between p53abn and HER2-status (ρ=0.438 p<0.0001) was significantly stronger (p<0.0001) than between serous histology and HER2-status (ρ=0.154; p=0.002). HER2-status did not have independent prognostic value for survival after correction for the molecular classification. Our study strongly suggests that molecular subclass-directed HER2-testing is superior to histotype-directed testing. This insight will be relevant for future trials targeting HER2.
U2 - 10.3390/cancers13010044
DO - 10.3390/cancers13010044
M3 - Article
SN - 2072-6694
VL - 13
SP - 44
JO - Cancers
JF - Cancers
IS - 1
ER -
