Common clinicopathological and immunological features of sarcomatoid carcinoma across organs: A histomorphology‐based cross‐organ study

Abstract

Sarcomatoid carcinoma (SC), which can occur in any organ, is a rare disease. To elucidate common characteristics of SC beyond organs, we evaluated clinicopathological and immunological features of SC defined by the single histological criterion beyond organs compared to randomly matched conventional carcinoma (non‐SC) adjusted for the disease stage. Immunological features were assessed by multiplex immunohistochemistry, comparing immune cell density in tumor tissues and tumor programmed death‐ligand 1 (PD‐L1) expression. A total of 101 patients with SC or non‐SC (31 lung, 19 esophagus, 22 pancreas, 15 liver, 4 bile duct, 6 kidney, 2 uterus and 2 ovary) were identified among 7197 patients who underwent surgery at our institute (1997‐2020). SC was significantly associated with worse survival (HR: 1.571; 95% CI: 1.084‐2.277; P = .017). The frequency of postoperative progression within 6 months was significantly higher for SC patients (54% vs 28%; P = .002). The immune profiling revealed the densities of CD8+ T cells (130 vs 72 cells/mm2; P = .004) and tumor‐associated macrophages (566 vs 413 cells/mm2; P < .0001) and the tumor PD‐L1 expression score (40% vs 5%; P < .0001) were significantly higher in SCs than in non‐SCs. Among 73 SC patients with postoperative progression, multivariate Cox regression analysis showed that immunotherapy tended to be associated with favorable survival (HR: 0.256; 95% CI: 0.062‐1.057; P = .060). Collectively, SCs shared clinicopathological and immunological features across organs. Our study can initiate to standardize the pathological definition of SC and provide a rationale for the investigation and development for this rare disease in a cross‐organ manner.

Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes

“…However, these efforts have so far focused on its most common subtypes, such as LUAD and LSCC [ 47 , 48 , 49 ]. In contrast to these conventional cancer types, PSC, this exceptionally aggressive lung cancer subtype, exhibited high CD8 + T cell density, tumor‐associated macrophages, and PD‐L1 expression and was linked to poorer survival and a higher incidence of postoperative progression [ 50 ]. Over the past several years, targetable molecular alterations such as MET exon 14 skipping mutations were identified [ 1 , 4 , 6 , 51 , 52 , 53 , 54 , 55 , 56 ].…”

“…Immunotherapy by ICB has shown unprecedented durable clinical responses in patients with various cancer types, including NSCLC [ 58 ]. ICB has been recently tested in PSCs and demonstrated promising clinical efficacy and tends to be associated with favorable survival [ 50 , 59 , 60 , 61 ]. However, the response rate is suboptimal in unselected patient populations [ 62 ].…”

Epigenomic signatures as circulating and predictive biomarkers in sarcomatoid renal cell carcinoma

“…RCC with sarcomatoid features (sRCC) exhibits an aggressive phenotype characterized by epithelial-to-mesenchymal transition (EMT) and responds poorly to vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) compared to non-sarcomatoid or "epithelioid" RCC [4][5][6] . Diagnosing sRCC is clinically important because it responds particularly well to immune checkpoint inhibitors (ICIs) [6][7][8][9][10] , potentially due to increased PD-L1 expression on tumor cells and prominent immune cell infiltration 6,[10][11][12][13] .…”