Pathology of clear cell carcinoma of the ovary: A basic view based on cultured cells and modern view from comprehensive approaches

Abstract

Clear cell carcinoma (CCC) is a distinct histologic type of ovarian carcinoma. CCC is more frequent in Japan than in the Western world. CCC is chemo‐resistant and often associated with paraneoplastic thromboembolism. Histologically, CCC is characterized by both cancer cells and stromas, being concordant with the cytological features. Clear cells contain abundant glycogen. Hepatocyte nuclear factor‐1β is a specific marker of CCC, and is likely to be involved in glucose metabolism. Extracellular matrix (ECM)‐deposited stroma and plasma cell‐rich inflammatory stroma are characteristic stromas of CCC. Studies using CCC cell lines showed that CCC cells produce ECMs and stimulate plasma cell differentiation in a paracrine manner. Most CCCs, as well as endometrioid carcinomas, originate from ovarian endometriosis. This is supported by molecular genetic data, although it remains unclear why different histologic types originate from the same precursor. CCC and endometrioid carcinoma are Lynch syndrome‐associated ovarian carcinomas. Recent comprehensive studies indicate that CCC is distinct not only in terms of histology but also in genomics, epigenomics and transcriptomics. This review summarizes the pathology of ovarian CCC along with a basic view based on cultured cells, and refers to recent genetic and omic data.

Screening of Differentially Expressed Iron Death-Related Genes and the Construction of Prognosis Model in Patients with Renal Clear Cell Carcinoma

“…Therefore, biomarkers related to iron death may be potential diagnostic biomarkers and therapeutic targets for patients with renal cancer [13]. As a common subtype of renal cell carcinoma, in recent years, many medical researchers have devoted themselves to studying the occurrence, development, and treatment of renal clear cell carcinoma [14][15][16][17][18]. Many studies have shown that different subtypes of renal cell carcinoma have different clinical characteristics and results.…”

Revisiting Glycogen in Cancer: A Conspicuous and Targetable Enabler of Malignant Transformation

“…These "clear cell" malignancies include cancers of the kidney, ovary, breast, endometrium, and colorectum (23)(24)(25)(26). The two most common clear cell cancersrenal and ovarian-have been well-characterized molecularly and histologically and provide useful systems to interrogate the roles of glycogen in tumorigenesis (26)(27)(28).…”

“…Additional research is also required to minimize adverse events that can occur when targeting metabolic processes which are important in both normal and malignant cells. This is highlighted by toxicities that have been reported from trials of 2DG against a range of advanced solid tumors, where the clinically tolerable dose of this agent was accompanied by significant adverse events including cardiac and gastrointestinal toxicities and neutropenia (28,29), with one patient experiencing a fatal cardiac arrest (96,102).…”

Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability

“…The most significant terms in Li signature were associated with meiosis, mismatch repair, and (unexpectedly) with glycogen biosynthesis ( Figure 4 ). Interestingly, there were previously only indirect links reported for the glycogen metabolism and Lynch syndrome ( Kato, 2020 ) or MSI ( Krausova and Korinek, 2014 ; Oh et al, 2016 ), e.g., through the Wnt signaling pathway ( Krausova and Korinek, 2014 ). In Danaher signature, the most significant terms were associated with mismatch repair and with somatic hypermutation of immunoglobulin genes and physiologically related processes: somatic diversification of immune receptors and immunoglobulins ( Figure 5 ).…”