CHAPTER 4 88 Immunohistochemical staining patterns In Table 2 immunohistochemical staining patterns are shown. The clear cell component in mixed uterine CCC was ER positive in 52% of patients, compared to 24% in pure uterine CCCs (p = 0.111). PR was positive in 29% of mixed uterine CCCs, compared to 5% in pure uterine CCCs (p = 0.046); while L1CAM was positive in 71% compared to 77% in mixed versus pure uterine CCCs respectively (p = 0.736). Within the endometrioid/serous component, loss of hormone receptors and L1CAM positivity was seen less frequently: ER positivity in 100%; PR positivity in 84%; L1CAM positivity in 24%. PMS2 staining was deficient in one case. Loss of MSH6 was present in 29% of mixed CCC, compared to 5% in pure uterine CCCs (p = 0.046). In case of mixed uterine CCCs, MSH6 and PMS2 expression was concordant in both components. MMR immunohistochemical and MSI results were concordant in all cases, except for one patient with a mixed uterine CCC showing MSI but intact immunohistochemical expression of both MSH6 and PMS2. Outcome Figure 2A shows that patients with mixed uterine CCC had a superior OS compared to patients with pure uterine CCC (log-rank test: p = 0.029), which is also the case for DSS and PFS (Supplementary D, p = 0.045 and = 0.034, respectively). As can be appreciated from Figure 2B, OS was inferior in the TP53 mutated subgroup (log-rank test: p = 0.003) whereas patients with POLE mutations and MSI showed very favorable outcome. DSS and PFS were inferior in the TP53 mutated subgroup as well (Supplementary D, p = 0.001 and p = 0.022). Remarkably, patients with negative L1CAM had a superior OS (p = 0.035, Figure 2C), as well as a superior DSS and PFS (Supplementary D, e molecular subgroups were correlated with OS, DSS and PFS (Table 4A-C). In multivariable Cox regression analysis however, histology was not correlated with outcome, whereas molecular subgroups were correlated with OS and DSS.
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