HER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy

Douglas Rottmann, Olivia Snir, Xinyu Wu, Serena Wong, Pei Hui, Alessandro D. Santin, Natalia Buza

Research output: Contribution to journalArticle

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Abstract

A recent phase II clinical trial showed increased progression-free survival in patients with HER2-positive endometrial serous carcinoma receiving trastuzumab in addition to carboplatin–paclitaxel chemotherapy. Similar to endometrial serous carcinomas, carcinosarcomas of the female genital tract have a dismal prognosis and could potentially benefit from new targeted therapeutic approaches. We aimed to systematically evaluate the characteristics of HER2 expression/amplification in gynecologic carcinosarcomas using standardized staining methods and scoring criteria. Tumors from 80 patients (65 uterine, 15 tubo-ovarian) were included, containing a serous (60%), endometrioid (10%), clear cell (3%), undifferentiated (3%), neuroendocrine (1%), or mixed (24%) carcinoma, and either a homologous (46%), or a heterologous (54%) sarcoma component. HER2 scores were assigned to both components per the 2007 and 2013 ASCO/CAP breast scoring criteria. A total of 13 cases (12 uterine, 1 ovarian, 16%) were HER2 positive (either by immunohistochemistry or FISH) using the 2013 criteria, while only 10 cases (9 uterine, 1 ovarian, 13%) were HER2 positive per the 2007 criteria. Nine cases showed a change in their HER2 immunohistochemical score between the two scoring systems, including two cases with a change in the overall HER2 status from negative (2007) to positive (2013). Heterogeneity of HER2 protein expression was observed in 38% of HER2-positive tumors, and a lateral/basolateral membranous staining pattern was common. The sarcoma component showed 2+, equivocal HER2 expression in five cases, one of which also demonstrated HER2 amplification by FISH. All HER2-positive carcinosarcomas had either a serous or a mixed carcinoma component, and all but one HER2-positive tumors were of uterine primaries. Our study demonstrates that gynecologic carcinosarcomas share similarities in their HER2 expression/amplification profiles to endometrial serous carcinomas, which should be taken into account when assessing their HER2 status to ensure appropriate patient selection for potential targeted HER2-based therapies in the future.

Original languageEnglish (US)
JournalModern Pathology
DOIs
StateAccepted/In press - Jan 1 2019

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Carcinosarcoma
Endometrial Neoplasms
Sarcoma
Neoplasms
Staining and Labeling
Carcinoma
Phase II Clinical Trials
Therapeutics
Patient Selection
Disease-Free Survival
Breast
Research Design
Immunohistochemistry
Drug Therapy
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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HER2 testing of gynecologic carcinosarcomas : tumor stratification for potential targeted therapy. / Rottmann, Douglas; Snir, Olivia; Wu, Xinyu; Wong, Serena; Hui, Pei; Santin, Alessandro D.; Buza, Natalia.

In: Modern Pathology, 01.01.2019.

Research output: Contribution to journalArticle

Rottmann, Douglas ; Snir, Olivia ; Wu, Xinyu ; Wong, Serena ; Hui, Pei ; Santin, Alessandro D. ; Buza, Natalia. / HER2 testing of gynecologic carcinosarcomas : tumor stratification for potential targeted therapy. In: Modern Pathology. 2019.
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abstract = "A recent phase II clinical trial showed increased progression-free survival in patients with HER2-positive endometrial serous carcinoma receiving trastuzumab in addition to carboplatin–paclitaxel chemotherapy. Similar to endometrial serous carcinomas, carcinosarcomas of the female genital tract have a dismal prognosis and could potentially benefit from new targeted therapeutic approaches. We aimed to systematically evaluate the characteristics of HER2 expression/amplification in gynecologic carcinosarcomas using standardized staining methods and scoring criteria. Tumors from 80 patients (65 uterine, 15 tubo-ovarian) were included, containing a serous (60{\%}), endometrioid (10{\%}), clear cell (3{\%}), undifferentiated (3{\%}), neuroendocrine (1{\%}), or mixed (24{\%}) carcinoma, and either a homologous (46{\%}), or a heterologous (54{\%}) sarcoma component. HER2 scores were assigned to both components per the 2007 and 2013 ASCO/CAP breast scoring criteria. A total of 13 cases (12 uterine, 1 ovarian, 16{\%}) were HER2 positive (either by immunohistochemistry or FISH) using the 2013 criteria, while only 10 cases (9 uterine, 1 ovarian, 13{\%}) were HER2 positive per the 2007 criteria. Nine cases showed a change in their HER2 immunohistochemical score between the two scoring systems, including two cases with a change in the overall HER2 status from negative (2007) to positive (2013). Heterogeneity of HER2 protein expression was observed in 38{\%} of HER2-positive tumors, and a lateral/basolateral membranous staining pattern was common. The sarcoma component showed 2+, equivocal HER2 expression in five cases, one of which also demonstrated HER2 amplification by FISH. All HER2-positive carcinosarcomas had either a serous or a mixed carcinoma component, and all but one HER2-positive tumors were of uterine primaries. Our study demonstrates that gynecologic carcinosarcomas share similarities in their HER2 expression/amplification profiles to endometrial serous carcinomas, which should be taken into account when assessing their HER2 status to ensure appropriate patient selection for potential targeted HER2-based therapies in the future.",
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