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. 2017 Jan 6;6(2):e1277308.
doi: 10.1080/2162402X.2016.1277308. eCollection 2017.

Clear cell ovarian cancers with microsatellite instability: A unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression

Brooke E Howitt  1 , Kyle C Strickland  1 , Lynette M Sholl  1 , Scott Rodig  1 , Lauren L Ritterhouse  1 , Dipanjan Chowdhury  2 , Alan D D'Andrea  2 , Ursula A Matulonis  3 , Panagiotis A Konstantinopoulos  3
Affiliations

Clear cell ovarian cancers with microsatellite instability: A unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression

Brooke E Howitt et al. Oncoimmunology. .

Abstract

Clear cell ovarian carcinoma (CCOC) represents a distinct histologic subtype of ovarian cancer associated with significantly worse prognosis across all stages and no effective therapeutic options. Here, we report a rare but clinically important cohort of CCOCs with microsatellite instability (MSI) (MSI-CCOCs), which are highly immunogenic and may thus be very responsive to immune checkpoint blockade. CCOCs with MSI exhibit a significantly higher number of CD8+ TILs, higher CD8+/CD4+ ratio, and higher PD-1+ TILs compared with microsatellite stable (MSS) CCOCs and compared with high grade serous ovarian cancers, which are the most common histologic subtype of ovarian cancer. Of note, PD-L1 expression in tumor cells or immune cells was noted in all cases of CCOCs with MSI. These observations open an alternative therapeutic avenue for a fraction of patients with CCOC and argue for the routine testing of CCOCs for MSI, a test that is not currently routinely performed.

Keywords: Clear cell ovarian cancer; PD-1; PD-L1; immunotherapy; microsatellite instability; tumor-infiltrating lymphocytes.

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Figures

Figure 1.
Figure 1.
Comparison of CD3, CD8+, CD8+/CD4+ ratio, and PD-1+ lymphocytes (A) between CCOCs with endometriosis vs. no endometriosis, (B) ARID1A/BAF250a loss vs. retention, and (C) between MSI-CCOCs and MSS-CCOCs.
Figure 2.
Figure 2.
Two representative MSS-CCOC and MSI-CCOC cases with staining results for CD3, CD8+, PD-1, and PD-L1 (PD-L1 staining in tumor cells).
Figure 3.
Figure 3.
Comparison of CD3, CD8+, CD8+/CD4+ ratio, and PD-1+ lymphocytes between (A) all CCOCs and all HGSOCs and between (B) MSI-CCOCs (n = 3) and all HGSOCs.
See this image and copyright information in PMC

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