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

• Published in: Modern pathology Vol. 33; no. 1; pp. 118 - 127
• Main Authors: Rottmann, Douglas, Snir, Olivia L., Wu, Xinyu, Wong, Serena, Hui, Pei, Santin, Alessandro D., Buza, Natalia
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 2020; Elsevier Limited
• Subjects: 13; 13/51; 38; 38/32; 45; 631/67/1517/1931; 692/53/2423; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Breast; Carboplatin; Carcinoma; Carcinosarcoma - genetics; Carcinosarcoma - metabolism; Carcinosarcoma - pathology; Chemotherapy; Endometrium; ErbB-2 protein; Fallopian Tube Neoplasms - genetics; Fallopian Tube Neoplasms - metabolism; Fallopian Tube Neoplasms - pathology; Female; Gene Amplification; Genital tract; Humans; Immunohistochemistry; Laboratory Medicine; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Molecular Targeted Therapy; Monoclonal antibodies; Paclitaxel; Pathology; Receptor, ErbB-2 - analysis; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Sarcoma; Trastuzumab; Tumors; Uterine Neoplasms - genetics; Uterine Neoplasms - metabolism; Uterine Neoplasms - pathology; Uterus
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/s41379-019-0358-x

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.