PD‐L1, RB1 and mismatch repair protein immunohistochemical expression in neuroendocrine carcinoma, small cell type of the uterine cervix

Abstract

Aim

Neuroendocrine carcinoma, small cell type of the uterine cervix (SmCC‐Cx) is a rare HPV‐ related tumor with limited therapeutic options. Merkel cell carcinoma, another virus‐associated neuroendocrine malignancy, has significant PD‐L1 expression rates. PD‐L1 expression has been reported in other malignancies of the cervix. We aimed to determine the prevalence of PD‐L1 in the context of mismatch repair protein (MMR) and RB1 expression status in SmCC‐Cx.

Methods And Results

Ten cases of SmCC‐Cx were tested for immunohistochemistry expression of PD‐L1, MLH1, MSH2, MSH6, PMS2, RB1, CD3, CD20 and HPV in situ hybridization (ISH). PD‐L1 expression was scored quantitatively (H‐score) in tumor cells and lymphocytes (tumoral/peritumoral). PD‐L1 positivity was seen in 7 cases, focal in most cases (H‐scores 3 to 140). 3/9 cases showed MMR deficiency. PD‐L1 expression levels correlated with MMR expression status: all 3 MLH1/PMS2‐deficient cases had a ≥5% PD‐L1 staining and an H‐score ≥10 (p=0.01). RB1 was lost in 4/9 cases, all PD‐L1+, but this correlation was not statistically significant.7/9 tumors were positive for HPV‐ISH; two of these had MLH1/PMS2 loss. Among the 2 HPV‐ISH negative tumors, one had MLS1/PMS2 loss.

Conclusions

PD‐L1 expression, predominantly focal, is seen in 70% of SmCC‐Cx, while loss of MMR expression is seen in 33% of SmCC‐Cx in our cohort. PD‐L1 expression in >10% of tumor cells is seen in a subset of tumors in association with loss of MMR expression. These patients may be amenable to immune checkpoint inhibitor therapy as a promising alternative for this aggressive disease.

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