Shotaro Korehisa

Clinical significance of programmed cell death-ligand 1 expression and the immune microenvironment at the invasive front of colorectal cancers with high microsatellite instability

Immunotherapy is reportedly effective in colorectal cancers (CRCs) with high microsatellite instability (MSI‐H); however, the specific cell types that respond to immune checkpoint therapy are unclear. Herein, we aimed to examine the expression of programmed cell death‐ligand 1 (PD‐L1) and related proteins in MSI‐H and microsatellite‐stable (MSS) CRCs to investigate the immune microenvironment at the tumors invasive front. The MSI status was retrospectively assessed in 499 patients undergoing surgical resection of primary CRC; of these, 48 were classified as MSI‐H. Propensity score matching was performed, and tissues from 36 and 37 patients with MSI‐H and MSS CRCs, respectively, were immunohistochemically evaluated for PD‐L1, PD‐1, CD8 and CD68. PD‐L1 expression was evaluated separately for tumor cells (PD‐L1 [T]) and tumor‐infiltrating myeloid cells in the stroma (PD‐L1 [I]). PD‐L1 (T) was positive in only 5.4% and 36.1% of MSS and MSI‐H CRCs, while PD‐L1 (I) was positive in 27% and 72.2% of these CRCs, respectively. The PD‐L1 (T) and PD‐L1 (I) expression levels in MSI‐H CRCs significantly correlated with poor differentiation, lymphatic invasion and vascular invasion (p < 0.05), and with early‐stage adenocarcinoma and high budding grade (p < 0.05), respectively. Significantly more PD‐L1 (I), CD8‐positive cells and CD68‐positive macrophages were present at the invasive front than in the central tumor in MSI‐H CRCs (p < 0.005). PD‐L1 was expressed on both tumor cells and CD68/CD163‐positive (M2) macrophages at the invasive front of MSI‐H CRCs. In conclusion, PD‐L1‐positive tumor cells and M2‐type tumor‐associated macrophages may contribute to tumor invasion and immune escape at the invasive front.

A case of mixed adenoneuroendocrine carcinoma (MANEC) arising in Barrett’s esophagus: literature and review

BackgroundMixed adenoneuroendocrine carcinoma (MANEC) is defined as a neoplasm composed of both exocrine and endocrine carcinomas, each comprising at least 30% of the tumor. MANEC can occur in various organs of the gastrointestinal tract, including the esophagus, stomach, and colon. We herein provide the first case report of surgically resected MANEC arising in Barrett’s esophagus (BE).Case presentationA 70-year-old man presenting with abdominal pain was referred to our hospital. Upper endoscopy showed a type 0-IIa + IIc elevated lesion adjacent to BE. According to a biopsy specimen, the elevated lesion was diagnosed as adenocarcinoma with neuroendocrine differentiation. No lymphatic or distant metastasis was detected in the preoperative examination. Laparoscopic distal esophagectomy and proximal gastrectomy were performed, and a diagnosis of MANEC in BE was determined according to the surgically resected specimen.ConclusionsA very rare case of MANEC in BE was detected. BE can be the origin of esophageal MANEC as well as adenocarcinoma. Due to the small number of esophageal or esophagogastric MANEC cases reported, further accumulation of such cases is necessary to recommend an optimal management strategy for esophageal or esophagogastric MANEC.

A novel histological examination with dynamic three-dimensional reconstruction from multiple immunohistochemically stained sections of a PD-L1-positive colon cancer

Programmed cell death‐ligand 1 (PD‐L1) expression is observed in patients with microsatellite instability‐high (MSI‐H) colon cancer, which is susceptible to immune checkpoint blockade. The aim of this study was to investigate the interrelationship between PD‐L1‐positive cells and cytotoxic T cells, lymphatic vessels and vascular endothelium by using histological examination with the three‐dimensional (3D) reconstruction of a PD‐L1‐positive colon cancer.