Histopathological features of HER2 overexpression in uterine carcinosarcoma: proposal for requirements in HER2 testing for targeted therapy

Yoshida, Hiroshi; Nishikawa, Tadaaki; Matsumoto, Koji; Mori, Masahiko; Hirashima, Yasuyuki; Takehara, Kazuhiro; Ariyoshi, Kazuya; Yonemori, Kan

doi:10.1007/s00428-021-03017-5

Cited by 16 publications

(21 citation statements)

References 33 publications

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“… 11 HER2 expression rates in carcinosarcoma range from 17% to 43% with higher expression rates in the carcinomatous component (up to 56%) when compared to the sarcomatous component (6%). 12 – 15 …”

Section: Discussionmentioning

confidence: 99%

“…A recent proposal toward standardization of reporting of HER2 in carcinosarcomas suggests that as with ESC, large tissue sections be evaluated to account for tumor heterogeneity and if possible metastatic lesions also be included. 15 Scoring including lateral/basolateral membranous staining was also recommended. 15 To date, no large-scale studies have been conducted to evaluate HER2 expression specifically in LVI of carcinosarcoma.…”

Section: Discussionmentioning

confidence: 99%

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Preferential human epidermal growth factor receptor 2 expression in myometrial and lymphovascular invasion of a uterine carcinosarcoma: A case report

Gillam

Pillappa

Idowu

et al. 2022

SAGE Open Medical Case Reports

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This case report describes a unique pattern of human epidermal growth factor receptor 2 expression in a patient with uterine carcinosarcoma. The endometrial tumor showed biphasic morphology composed of serous carcinoma and a heterologous high-grade sarcoma component. Human epidermal growth factor receptor 2 immunostaining showed positive (3+) expression in foci of myoinvasion, lymphovascular invasion, and lymph node metastasis but was negative in both the endometrial surface tumor and sarcomatous component. Fluorescent in situ hybridization testing for human epidermal growth factor receptor 2 confirmed no amplification within the endometrial surface carcinoma component and amplification of the lymphovascular invasion component. As the use of human epidermal growth factor receptor 2 immunohistochemical evaluation becomes more commonplace for therapeutic consideration in patients with uterine carcinosarcoma, interpretation of the immunohistochemical should be performed preferentially on large tissue sections including both a surface, myoinvasive portions, and suspected areas of lymphovascular invasion and lymph node metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Preferential human epidermal growth factor receptor 2 expression in myometrial and lymphovascular invasion of a uterine carcinosarcoma: A case report

Gillam

Pillappa

Idowu

et al. 2022

SAGE Open Medical Case Reports

View full text Add to dashboard Cite

show abstract

“…Our evaluation method has been used in the ongoing phase 2 clinical trial of HER2 ADC in patients with recurrent/metastatic UCS (STATICE trial)[ 52 ]. In this study, we identified that most UCS showed lateral/basolateral staining patterns (Figure 2 ), similar to endometrial serous carcinoma and gastric adenocarcinoma[ 39 ]. Based on our previous observations, we concluded that a HER2 testing protocol for UCS should contain the following requirements[ 39 ]: (1) Established pre-analytical factors of HER2 IHC[ 32 , 33 ] should be carefully controlled; (2) One representative section containing carcinoma components should be submitted from the hysterectomy specimen; (3) HER2 IHC should be performed using an IVD kit or a laboratory-developed test with appropriate quality control[ 32 , 33 ]; (4) Positive lateral/basolateral membranous staining patterns should be considered as positive, according to the 2016 ASCO/CAP gastric cancer criteria[ 32 ]; and (5) The proportion of HER2 expressing tumor cells should be determined as an approximate number of HER2-positive tumor cells divided by that of total tumor cells (both carcinoma and sarcomatous elements).…”

Section: Her2 Testing In Uterine Carcinosarcomamentioning

confidence: 98%

“…In endometrial cancer, HER2 testing has become more clinically relevant in serous carcinoma[ 37 ] and carcinosarcoma[ 38 , 39 ], with the accumulating knowledge of HER2 testing accompanied by ongoing therapeutic developments.…”

Section: Her2 Testing In Endometrial Cancer; Pathological Perspectivementioning

confidence: 99%

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Human epidermal growth factor receptor 2 targeted therapy in endometrial cancer: Clinical and pathological perspectives

Saito¹,

Yoshida²,

Nishikawa³

et al. 2021

WJCO

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Endometrial cancer is the most common gynecological cancer in developed countries, and its incidence has increased. The majority of patients with endometrial cancer have an early disease and favorable prognosis; however, a significant proportion of endometrial cancer, which mainly comprises high-grade or type II endometrial cancer such as serous, clear cell, and carcinosarcoma, shows advanced/recurrent disease and dismal prognosis. Novel therapeutic development is required for patients with aggressive endometrial cancers. Recent genomic and immunohistochemical analyses revealed human epidermal growth factor receptor 2 (HER2) overexpression/gene amplification in 20%-40% of patients with type II endometrial cancer. Historically, HER2 targeted therapy has been developed for various major cancers, including breast and gastric cancer. Notably, recent advances in HER2 targeted therapy for patients with type II endometrial cancer are also expected to change. Simultaneously, an optimized HER2 test for endometrial cancer as companion diagnostics should be established. In this review, we summarize the recent findings on endometrial cancer, current treatment, optimized HER2 testing, key clinical trials on HER2 targeted therapy, and future directions in aggressive endometrial cancer, including serous carcinoma and carcinosarcoma.

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Discordances in expression of human epidermal growth factor receptor 2 between primary and metastatic uterine carcinosarcoma: A proposal for HER2-targeted therapy specimen selection

Yoshida¹,

Mizoguchi²,

Saito³

et al. 2023

Annals of Diagnostic Pathology

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Histopathological features of HER2 overexpression in uterine carcinosarcoma: proposal for requirements in HER2 testing for targeted therapy

Cited by 16 publications

References 33 publications

Preferential human epidermal growth factor receptor 2 expression in myometrial and lymphovascular invasion of a uterine carcinosarcoma: A case report

Preferential human epidermal growth factor receptor 2 expression in myometrial and lymphovascular invasion of a uterine carcinosarcoma: A case report

Human epidermal growth factor receptor 2 targeted therapy in endometrial cancer: Clinical and pathological perspectives

Discordances in expression of human epidermal growth factor receptor 2 between primary and metastatic uterine carcinosarcoma: A proposal for HER2-targeted therapy specimen selection

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