Clinicopathologic profile, immunophenotype, and genotype of CD274 (PD-L1)-positive colorectal carcinomas.
The CD274 (PD-L1)/PDCD1 (PD-1) pathway is crucial for the modulation of immune responses and self-tolerance. Aberrantly expressed CD274 allows tumor cells to evade host immune system and is considered to be a mechanism of adaptive immune resistance. Inhibition of the CD274/PDCD1 immune checkpoint offers a promising new therapeutic strategy. Although CD274-expressing tumor cells have been identified in different types of tumors including colorectal cancer, clinicopathologic profile of these CD274-positive tumors has not been extensively studied. In this study, 454 primary colorectal carcinomas were analyzed histologically and immunohistochemically for CD274, mismatch repair (MMR) proteins, intestinal differentiation marker (CDX2), and stem cell markers (ALCAM, ALDH1A1, and SALL4). CD274-positive colorectal carcinomas (54/454 (12%)) usually (83%) involved the right or transverse colon with poorly differentiated and solid/medullary histology. On the basis of multivariate logistic regression analysis, CD274 positivity was significantly associated with poorly differentiated histotype (OR: 3.32; 95% CI: 1.46-7.51; P=0.004), MMR deficiency (OR: 10.0; 95% CI: 4.66-21.5; P<0.001), and 'stem-like' immunophenotype defined by the loss or weak expression of CDX2 and ALCAM-positivity (OR: 5.51; 95% CI: 1.66-18.3; P=0.005). Mutation analysis of 66 arbitrary selected colorectal carcinomas revealed that CD274-positive tumors usually (88%) carried the BRAF V600E mutation. Thus, colorectal carcinomas defined by CD274 positivity displayed features associated with tumors arising via the serrated neoplasia pathway. Moreover, colorectal carcinomas characterized by lack of CDX2 and prominent expression of ALCAM frequently (71%) showed CD274 positivity. This might suggest association of CD274 expression with 'stem-like' phenotype. Further evaluation of a larger cohort or experimental analyses would be needed to confirm this notion.
Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.|Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.
Shingo
S
Inaguma
Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Jerzy
J
Lasota
Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Zengfeng
Z
Wang
Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Anna
A
Felisiak-Golabek
Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.
Hiroshi
H
Ikeda
Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Markku
M
Miettinen
D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D000071616:CDX2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053843:DNA Mismatch Repair / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D050697:Retinal Dehydrogenase; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020410:Activated-Leukocyte Cell Adhesion Molecule
D000444:Aldehyde Dehydrogenase; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD; D060890:B7-H1 Antigen; D000071616:CDX2 Transcription Factor; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D048493:Proto-Oncogene Proteins B-raf; D050697:Retinal Dehydrogenase; D014157:Transcription Factors; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C472575:SALL4 protein, human; C510223:ALDH1A1 protein, human; C482119:BRAF protein, human