Clinical and pathological analysis of companion diagnostic testing of microsatellite instability-high for pembrolizumab in gynaecologic malignancy

• Published in: Japanese journal of clinical oncology 2022-02, Vol.52 (2), p.128-133
• Main Authors: Takeda, Takashi, Tsuji, Kosuke, Kobayashi, Yusuke, Banno, Kouji, Aoki, Daisuke
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal, Humanized; Child; DNA Mismatch Repair - genetics; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - genetics; Female; Humans; Immunohistochemistry; Microsatellite Instability; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Retrospective Studies
• ISSN: 1465-3621; 1465-3621
• DOI: 10.1093/jjco/hyab175

Abstract Background Microsatellite instability-high is a known biomarker for anti-PD-1/PD-L1 immune checkpoint therapy. It is also a known tumour feature of Lynch syndrome, detected most frequently in endometrial cancer. However, it remains unclear how microsatellite instability testing is carried out in the clinical field. Methods Ninety-nine patients with gynaecological malignant tumours who underwent microsatellite instability testing as a companion diagnosis for pembrolizumab and 16 patients who previously underwent microsatellite instability testing as a screening for Lynch syndrome were recruited. Clinical information, microsatellite instability status, outcomes, genetic assessments and information about cancer tissue were retrospectively analysed. Results Ninety-nine patients had 101 gynaecologic malignant tumours including 26 endometrial, 38 ovarian and 28 cervical cancers, 9 with other tumours including 2 synchronous endometrial and ovarian cancers. All tissue samples were successfully tested, even though some were ≥10-year-old samples. Three cases (3.0%, 3/99) showed microsatellite instability-high; all cases were endometrial cancers with one case of synchronous endometrial and ovarian cancer [11.5% (3/26) in endometrial cancer, 2.6% (1/38) in ovarian cancer], and there was no microsatellite instability-high in cervical and other cancers. One of the endometrial cancer patients received pembrolizumab treatment, but finally died of cancer. Two other cases underwent genetic testing; both were diagnosed as Lynch syndrome. Six cases (37.5%) showed microsatellite instability-high in screening for Lynch syndrome. Conclusions Microsatellite instability-high was less commonly detected as a companion diagnosis for pembrolizumab in unselected gynaecologic patients. Genetic counselling should be always provided along with treatment selection. Three percent (3/99) of advanced or recurrent gynaecologic malignancies showed MSI-H as a companion diagnosis for pembrolizumab, mostly detected in endometrial cancer (11.5%, 3/26).