S100‐stained perineural invasion is associated with worse prognosis in stage I/II colorectal cancer: Its possible association with immunosuppression in the tumor

Abstract

Perineural invasion (PNI) is known as a poor prognostic factor in colorectal cancer (CRC). Although histopathological evaluation of PNI is usually conducted on hematoxylin and eosin (HE)‐stained sections (HE‐PNI), it remains controversial whether PNI can be precisely evaluated only by HE‐staining, and its concise mechanisms causing worse prognosis remains elusive. In this study, we examined the impact of PNI evaluated by S‐100‐immunostaining (S100‐PNI) on postoperative mortality in 279 consecutive CRC patients and further investigated its association with the tumor immune microenvironment. S100‐PNI was present in 67.3% of tumors whereas HE‐PNI was present in 18.5%. A 5‐year cumulative incidence of death in the S100‐PNI‐positive group was significantly higher than that in the S100‐PNI‐negative group. Further statistical analyses revealed that S100‐PNI was an independent prognostic factor of all‐cause mortality in stage I/II but not in stage III/IV. Importantly, S100‐PNI was associated with the altered tumor immune microenvironment. Infiltrating immune cell profiling revealed that stromal lymphocytic reaction, which was inversely correlated with postoperative mortality, was significantly reduced in S100‐PNI‐positive tumors compared to S100‐PNI‐negative tumors in stage I/II. These results indicated that S100‐PNI was a poor prognostic factor in stage I/II CRC with possible association with immunosuppression in the tumor.

Transcriptome analyses reveal new insights on key determinants of perineural invasion in high-grade serous ovarian cancer

“…Our first step was to determine whether PNI induced Schwann cell dedifferentiate by testing the level of GFAP protein. Anti-GFAP and anti-S100 antibodies were used to stain sections of tumor tissue with and without PNI ( Deborde et al, 2016 ; Fukuda et al, 2022 ). As compared with PNI-negative samples, nerves showed higher GFAP levels in PNI-positive samples ( Figure 5C ).…”

“…Anti-GFAP and anti-S100 antibodies were used to stain sections of tumor tissue with and without PNI (Deborde et al, 2016;Fukuda et al, 2022). As compared with PNI-negative samples, nerves showed higher GFAP levels in PNI-positive samples (Figure 5C).…”

The depth of perineural invasion is an independent prognostic factor for stage II colorectal cancer

“…Firstly, as a single-center retrospective study, our findings may be limited by potential information bias and may not be generalizable to other populations. Secondly, we did not conduct immunostaining for neuropeptide markers in patient specimens [ 26 ], which may have affected the accuracy of the PNI classifications. Finally, due to the insufficient number of dMMR patients, it is difficult to explain the relationship between dMMR and PNI, and the relevant study is being conducted.…”

Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

“…The primary screening method for PNI involves the use of hematoxylin and eosin (HE) staining, with immunohistochemistry (IHC) employing S100 markers enhancing the detection accuracy. Research indicates that shortcomings in identifying PNI via HE can be addressed through S100 immunostaining, thereby quantification of PNI by S100 is a potential method for prognosis prediction [29,30]. Advances have also been made in molecular methodologies that leverage markers associated with PNI.…”