酒井 康弘

Cancer genome testing routinely reports driver alterations, mutational signatures, and DNA repair states, yet key clinical phenotypes—tumor behavior, relapse risk, and chemoresistance—are not fully explained by geno- type alone. Deleted in split-hand/split-foot 1 (DSS1) is a small, acidic, intrinsically disordered protein conserved across eukaryotes and shared by several large multiprotein assemblies, making it a plausible functional modifier of these phenotypes. This review summarizes DSS1 biology from the perspective of clinical laboratory medi- cine, focusing on how DSS1 links RNA metabolism, R-loop homeostasis, and homologous recombination repair (HRR) and how this linkage may inform biomarker development. Mechanistically, DSS1 behaves as a stabilizing “molecular glue” in protein complexes and serves as a core component of RNA export/quality-control modules, including TREX-2 and the TREX-2.1/REX complex, which regulate co-transcriptional messenger ribonucleop- rotein remodeling, nuclear export, and RNA surveillance—processes closely tied to R-loop (DNA:RNA hybrid) control and transcription-coupled DNA damage. DSS1 is also an obligate cofactor of BRCA2: DSS1 binding sta- bilizes BRCA2, improves its solubility, and limits off-target interactions, supporting repair-competent BRCA2 in the nucleus. We then review clinicopathological evidence that DSS1 dysregulation correlates with cancer behav- ior, including shorter relapse-free survival and a chemoresistant phenotype. Finally, we propose that DSS1-low, BRCA-proficient tumors may acquire BRCAness, providing a rationale for PARP inhibitor responses beyond cur- rent BRCA-focused companion diagnostics, and we outline how standardized DSS1 measurement (mRNA and/ or protein), integrated with BRCA status and other HRR-related signatures, could refine molecular testing and therapeutic stratification in routine practice.

Accurate distinction between pulmonary metastases of oral squamous cell carcinoma (OSCC) and primary lung squamous cell carcinoma (LSCC) is critical for clinical management, but practical immunohistochemical markers remain limited in routine practice. We screened three public mRNA expression datasets, GSE84846 for OSCC and The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium for LSCC, and selected six candidate markers for immunohistochemical evaluation in 39 OSCC and 92 LSCC specimens. Among them, keratin 1 (K1; encoded by KRT1) and keratin 18 (K18; encoded by KRT18) showed the most significant differential expression between OSCC and LSCC (both p < 0.0001). K1 was predominantly expressed in OSCC and rarely in LSCC, whereas K18 showed the opposite pattern. K1 showed high specificity (0.989) and an odds ratio of 117.8, while K18 showed a specificity of 0.974 and an odds ratio of 59.1. Receiver operating characteristic analysis confirmed strong discriminatory performance for K1 (AUC, 0.865) and K18 (AUC, 0.872). In four whole-exome sequencing-confirmed pairs of primary OSCC and lung metastases, staining patterns for both markers were concordant between the primary oral tumors and pulmonary lesions. These findings support K1 and K18 as practical markers for distinguishing pulmonary metastases of OSCC from primary LSCC.

Prospero homeobox protein 1 (PROX1) is aberrantly expressed in tumors, including neuroendocrine neoplasms (NENs); however, the detailed expression pattern remains elusive. This study aimed to immunohistochemically assess PROX1 expression. Immunohistochemistry (IHC) for PROX1 was performed on tissue microarrays of normal tissues (n = 107), NENs (n = 152) (small cell lung carcinoma [SCLC], lung carcinoid [LC], gastroenteropancreatic-NEN [GEP-NEN], esophageal neuroendocrine carcinoma [ENEC], medullary thyroid carcinoma [MTC], neuroblastoma [NB], and pheochromocytoma [PHEO]), and non-NENs (n = 469). In normal tissues, PROX1 was expressed in lymphatic endothelial cells and a subset of epithelial cells in the gastrointestinal tract and the distal convoluted tubules. In NENs, the positive expression was observed in the nucleus of tumor cells in 19/26 SCLC (73.1%), 13/16 LC (81.3%), 10/15 GEP-NEN (66.7%), 2/2 ENEC (100%), 17/43 MTC (39.5%), 1/25 NB (4.0%), and 0/25 PHEO (0%). Although PROX1 was negative in many non-NENs, our analysis revealed high expression in certain cases with medulloblastoma and one case with juvenile granulosa cell tumor. PROX1 was expressed in specific cases with epithelial NENs and some cases with non-NENs. Analysis of PROX1 should provide insights into the molecular characteristics of distinct tumors.

Background and aims: Capillary Cup® is a novel finger-stick blood collection device equipped with separation float technology to effectively isolate plasma and blood cell layers. This study aimed to evaluate its analytical equivalence compared to venipuncture sampling in clinical chemistry, complete blood count, and hemoglobin A1c testing. Methods: Blood samples were collected from 63 healthy participants for clinical chemistry and hemoglobin A1c tests and 67 for complete blood count tests. Discrepancies between the Capillary Cup® and venipuncture sampling results were analyzed using the 2025 Clinical Laboratory Improvement Amendments (CLIA) acceptance limits and total allowable error (TEA) thresholds. Results: The Capillary Cup® samples showed strong linear correlations with venipuncture samples across proteins, transaminases, kidney function markers, lipids, C-reactive protein, blood cell and platelet counts, white blood cell differentials, hemoglobin, hematocrit, and Wintrobe's indices (r = 0.740–0.999, P < 0.0001). Hemoglobin A1c was accurately measured alongside other clinical chemistry markers in a single kit (r = 0.976, P < 0.0001). All values met the 2025 CLIA acceptance limits, and most also met the TEA thresholds. Minor deviations were observed for creatinine, triglycerides, and C-reactive protein, as well as for platelet counts—potentially affected by activation and aggregation—but all remained within acceptance limits and demonstrated preserved linearity. Conclusions: The Capillary Cup® provides analytically equivalent results to venipuncture for all tested parameters. It is easy to use, reduces waste, and is a potential alternative for at-home health monitoring, addressing challenges in venous access, and reducing iatrogenic blood loss risk in clinical practice.