case_images: PMC8544124_01
case_images: Heterogeneous morphology, MMR protein expression and PD-L1 expression patterns of the 2 synchronous rectal tumours (masses A and B) in the LS patient. (A and G) HE staining of masses A and B showing the classic protruding pattern of adenocarcinoma growth. The IHC staining of mass A showed intact expression of MLH1 (B), PMS2 (C), MSH2 (D), and PD-L1 (F) in addition to loss of expression of MSH6 (E). Mass #B showed intact expression of MLH1 (H), PMS2 (I), MSH2 (J), MSH6 (K) and PD-L1 (L). All images were collected at 100x magnification.
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case_images: Mass A demonstrated deficient MMR (dMMR); specifically, there was an absence of MSH6 protein but normal expression of MLH1, MSH2 and PMS2. Mass B expressed all 4 MMR proteins and was therefore deemed to have proficient MMR (pMMR) (Figure 1). Mass B presented strong positive PD-L1 expression; however, it had less than 1% positivity for tumour cells and 5% positivity for immune cells (Figure 1).
case_images: The patient's pedigree. The proband had rectal cancer and carried the MSH6 p.R495* germline mutation. Similarly, the individuals (the patient's mother and the patient's brother) without cancers carried the MSH6 p.R495* germline mutation. One of the patient's uncles had colon cancer but did not undergo NGS assessment.
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case_images: In addition, one of the patient's uncles was affected by colon cancer without detailed information (Figure 2).
case_images: Assessment of the TIME via multiplex IHC (mIHC). (A and F) The green fluorescence indicates CD8+ T cells. (B and G) The pink fluorescence indicates PD-1 expression. (C and H) The yellow fluorescence indicates CD68 expression. (D and I) The Orange fluorescence indicates PD-L1 expression. (E and J) The pictures show all layers merged.
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case_images: In particular, the CD8+ T cell proportions in the two CRC tumours were 9.07% and 6.63%, respectively (Figure 3). CD8+PD-1+ T cells and CD68+PD-L1+ macrophages (Figure 3). The HLA-I molecules were of the hla-b44 supertype, which are positive indicators for immunotherapy. Considering the numerous markers indicating the potential of immunotherapy, including MSI-H, high TMB, presence of CD8+PD-L1+ cells and CD68+PD-L1+ macrophages, and the HLA-b44 supertype, ICI strategies had the potential to be effective.