Pathology International最新文献

Air transport of FFPE cancer tissue samples led to increased DNA fragmentation, primarily due to radiation exposure rather than temperature changes or freeze-thaw cycles. While overall degradation was minor, critical samples requiring high nucleic acid integrity may benefit from local testing or research. Avoiding air transport could help mitigate potential risks and ensure reliable results.

The incidence of upper tract urothelial carcinoma (UTUC) in Taiwan is high, characterized by aggressive clinical behavior and a tendency to be more invasive at diagnosis. Identifying tumorigenic genes remains an important challenge. Myc binding protein 2 (MYCBP2) regulates the cAMP, p38MAPK, TSC/mTOR, and autophagy signaling pathways in mammalian cells. MYCBP2 dysfunction has been associated with poor prognosis in leukemia, melanoma, colon, and prostate cancer. Its role in UTUC needs to be clarified. We investigated the expression of MYCBP2 in UTUC and its relationship to patient outcomes. MYCBP2 expression levels were assessed by immunohistochemistry in 110 tissue samples from UTUC patients. Higher MYCBP2 protein expression was significantly correlated with worse disease-free survival (p = 0.001) and cancer-specific survival (p = 0.007). The major clinicopathological characteristics associated with MYCBP2 expression were stage, lymphovascular invasion, distant metastasis, recurrence, and cancer death. Based on multivariate analysis, pathological stage (HR:2.31, p = 0.017) and MYCBP2 expression (HR:2.75, p = 0.015) were significant predictors of disease-free survival in UTUC. MYCBP2 is elevated in UTUC cell lines compared with immortalized uroepithelial cells. Knocking down MYCBP2 significantly suppressed cellular migration and invasion activity in BFTC909 cells. In conclusion, MYCBP2 expression might predict poor survival among UTUC patients.

Kidney injury molecule-1 (KIM-1) is a potential prognostic marker of advanced-stage clear cell renal cell carcinoma (ccRCC) and is associated with tumor immunogenicity. Little is known about its role in early-stage ccRCC, especially in pathological T1b (pT1b) disease, which shows a higher recurrence rate than pT1a disease. Resected specimens from 112 pT1b ccRCC cases were reviewed and immunohistochemically analyzed for KIM-1 expression. High membranous KIM-1 expression was defined as H score ≥ 140, based on the immunoreactive intensity and area, and cytoplasmic expression in ≥ 10% of cancer cells was considered as high cytoplasmic KIM-1 expression. KIM-1 expression status was compared with clinicopathological variables, including tumor-associated immune cell (TAIC) status. Among the 112 cases, high membranous and cytoplasmic KIM-1 expression was observed in 30 (27%) and 38 (34%) cases, respectively. High membranous KIM-1 expression was significantly associated with a higher nuclear grade, tumor necrosis, hot TAIC status, and shorter recurrence-free survival (RFS) and cancer-specific survival, whereas high cytoplasmic expression was only related to a higher nuclear grade. Multivariate Cox regression analysis revealed that high membranous KIM-1 expression and tumor necrosis were independent predictors of shorter RFS. Our results indicate that membranous KIM-1 expression could be a biomarker for predicting postnephrectomy recurrence in pT1b ccRCC.

Advances in cancer biology have been achieved by the identification of oncogenes and tumor suppressor genes through the remarkable progression of next-generation sequencing. New techniques, such as single-cell analysis, help uncover cancer progression and heterogeneity. Reverse genetic screenings, including methods like random mutagenesis via retroviruses, transposons, RNA interference, and CRISPR, are useful for exploring gene functions and their roles in cancer. Especially in random mutagenesis, CRISPR screening and its modifications have recently emerged as powerful tools due to their comprehensiveness and simplicity in inducing genetic mutations. Initially, CRISPR screening focused on analyzing biological phenotypes in a cell population. It has since evolved to incorporate advanced techniques, such as combining single-cell and spatial analyses. These developments enable the investigation of cell-cell and spatial interactions, which more closely mimic In Vivo microenvironments, offering deeper insights into complex biological processes. These approaches allow for the identification of essential genes involved in cancer survival, drug resistance, and tumorigenesis. Together, these technologies are advancing cancer research and therapeutic development.

Growing experience has correlated the histomorphological characteristics of clear cell renal cell carcinoma (ccRCC), ranging from cytoplasmic features to architectural patterns and tumor immune microenvironment, with clinical outcomes. However, further assessment is needed to determine which of these histologic parameters best correlate with outcomes of interest, especially response to tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Herein, we evaluated four histologic parameters: (i) World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade; (ii) clear and eosinophilic cytological phenotypes; (iii) immunophenotypes; and (iv) vascularity-based architectural classification, using hematoxylin and eosin-stained whole slide images for The Cancer Genome Atlas (TCGA) ccRCC cohort (n = 433). We then correlated these parameters with gene expression signatures associated with TKI and ICI response. Multivariate analysis found that the cytological phenotype and vascularity-based architectural classification were independently associated with an angiogenesis-related gene signature (both p < 0.05). Conversely, WHO/ISUP grade and immunophenotype were independently associated with effector T-cell and immune checkpoint gene signatures (both p < 0.05). In conclusion, histologic parameters, including cytological features, architectural patterns, and tumor immune microenvironment, are associated with gene signatures related to therapy response, with different parameters informative for TKIs versus ICIs. These findings may help guide prospective validation studies.

Adenosquamous carcinoma is an uncommon type of cancer that comprises malignant squamous and glandular components. We present a case of human papillomavirus (HPV)-positive adenosquamous carcinoma of the anorectum, which exhibited extensive pagetoid spread, in a 70-year-old woman. The tumor had spread from the lower rectum to the perianal skin and was removed through a combined endoscopic and transanal surgical procedure. Histological examination revealed three morphologically distinct components: adenocarcinoma in the lower rectum, squamous intraepithelial neoplasia with a minor invasive squamous cell carcinoma component in the anal canal, and pagetoid spread of adenocarcinoma extending to the perianal skin. HPV18 DNA and diffuse p16 expression were detected in all three components, suggesting the integration of HPV and a histogenetic relationship among these morphologically distinct components. This case indicates that HPV-associated adenosquamous carcinoma also occurs in the anal canal, similar to the uterine cervix, and may present as secondary Paget's disease.

This study presents the ultrastructural and immunohistochemical findings of a gastric bizarre leiomyoma arising in the vestibule of a 79-year-old male. Histologically, loosely proliferating tumor cells consist of large, multinucleated, bizarre nuclei with intranuclear inclusions and abundant cytoplasm-containing vacuoles. A murky line was apparent between the tumor cells and eosinophilic and heterogenous stroma-like areas. Immunohistochemically, tumor cells exhibited positively stained dot patterns of α-smooth muscle actin and caldesmon, which were distributed in the cytoplasm of tumor cells and stroma-like regions. Ultrastructurally, tumor cells exhibited extended and complex cytoplasmic processes comprising the fascicles of filamentous fibers. These structures were also detected in the apparent stroma-like regions observed histologically and were consistent with the α-smooth muscle actin- and caldesmon-immunopositive dot structures. The original stromal areas remained as considerably narrow gaps between tumor cells with extended cytoplasmic processes. To the best of our knowledge, this is the first report detailing the unique ultrastructural and immunohistochemical characteristics of tumor cells and the limited stromal composition of an extremely rare primary gastric bizarre leiomyoma.