Immunohistochemical Expression of Programmed Death Ligand-1 (PDL-1) in Colorectal carcinoma and Its Correlation with Stromal Tumor Infiltrating Lymphocytes

Abstract

Objectives: Detection of Immunohistochemical (IHC) expression of PDL-1 by tumor cells and stromal tumor infiltrating lymphocytes (TILs) in colorectal carcinoma, to investigate the possibility of using it as a targeted therapy, as well as, correlation of this expression with the clinico-pathologic parameters of the tumors. Materials and Methods: Colorectal tissue sections were collected from 60 colectomy specimens were taken from Kasr El Ainy Hospital, Faculty of Medicine, Cairo University. Exclusion criteria included cases with missing data and cases who received chemotherapy or radiotherapy. IHC expression of PDL-1 was investigated in tumor cells (T) and stromal TILs separately. PDL-1 positivity was defined as PDL-1 expression on ≥ 5% of membranous positive cell staining of any intensity. Results: PDL-1 (T) expression was detected in 25% of cases and showed statistically significant correlation with higher tumor grade and right sided colon tumors (P value < 0.05). PD-L1 stromal TILs expression was detected in 38.3 % of cases. Insignificant statistical relation between Stromal TILs PDL-1 expression and the tumor extent (T) was detected (P value = 0.07), however, the expression of PDL-1 in lymphocytes was inversely proportional to the tumor extent (invasion). There were linear relation between PDL-1 expression stromal (TILs) (33.3%) and PDL-1 expression in tumor cells (28.2%) and positive lympho-vascular invasion but it was statistically insignificant (P value = 0.4 and 0.2 respectively). Despite there were no statistical relation between either PDL-1 (T) and PDL-stromal TILS and Perineural invasion (P value =1 and 0.5) but inverse relation was noticed with more PDL-1 expression in tumor cells (24.5%) and TILS (40.8%) with negative Perineural invasion. Conclusion: Our results supported PDL-1 expression in CRC by both TC and TILs, with higher expression in subset of tumors that are high grade highlighting them as candidates for anti-PD-1/PDL-1 therapy.

Correlation Between Programmed Cell Death Ligand1 (PD-L1) Expression and Clinical Parameters in Colorectal Carcinoma

“…Although PD-L1 expression was more common in rightsided tumors with female predominance similar to previous studies, 3,18 they didn't approach a statistic significance. From our point of view, this attributed to the small sample size of the study.…”

Programmed death ligand 1 (PD-L1) in colon cancer and its interaction with budding and tumor-infiltrating lymphocytes (TILs) as tumor-host antagonists

“…In our study, TILs > 5% and dMMR were the only two parameters that correlated reproducible and significantly with PD-L1 positivity in all three settings (overall, TPS, IC) with both antibodies. Interestingly, overall and IC PD-L1 positivity with both antibodies were significantly linked to more favourable clinicopathological features like lower pT, pN, and M and less L1 and V1, [40,41,48,49].…”

“…Studies focussing on PD-L1 immunohistochemistry in CC are very heterogenous in their scoring conventions, regarding, for example, amount of tissue for PD-L1 assessment (tissue micro array versus whole tumor slide), staining pattern (membranous versus cytoplasmatic), and cutoffs for PD-L1 positivity which make them difficult to compare. Elfishawy et al, for example, measured membranous staining only in tumor cells and stromal TILs and defined positivity as > 5% [40]. Wang et al assessed PD-L1 in duplicate cores of 1 mm each on tissue micro arrays and also only evaluated membranous staining on tumor cells as well as immune cells, using stepwise cutoffs from < 1 to > 10% [41].…”

PD-L1 as a Prognostic Factor in Early-Stage Colon Carcinoma within the Immunohistochemical Molecular Subtype Classification

“…CRC is considered to be a cold tumor with a low PD-L1 expression compared with other solid tumors such as lung cancer, renal cell carcinoma and urothelial carcinoma. PD-L1 expression in CRC is not frequently observed in tumor cells [ 29 , 38 , 44 , 45 , 46 ], although this may not be the case for all clones. Accordingly, the PD-L1 expression in our study with the SP142 clone mostly occurred in the immune cells of the tumor-related stroma, and not in any tumor cells ( Figure S2a,b ).…”