Medical Molecular Morphology最新文献

The purpose of this study was to assess the clinicopathological features of oropharyngeal cancer patients in Jordan based on their HPV status. Sixty-nine biopsies from two hospitals were included. Tissue microarrays were prepared from formalin-fixed paraffin-embedded (FFPE) specimens and stained with antibodies for CDKN2A/P16, EGFR, PI3K, PTEN, AKT, pS473AKT, PS2mTOR, and TIMAP. The cohort was divided according to P16 expression. Chi-square test and survival analyses were employed to evaluate the variations among the study variables and determine the prognostic factors, respectively. P16 expression was found in 55.1% of patients; however, there was no significant association between P16 expression and the patients' clinicopathological features. The Kaplan-Meier test revealed that smoking in P16-positive group and younger age (< 58 years) negatively impacted disease-free survival (DFS) (P = 0.04 and P = 0.003, respectively). Multivariate Cox regression test indicated that smoking, age, PI3K, and AKT were negative predictors of DFS (P = 0.021, P = 0.002, P = 0.021, and P = 0.009, respectively), while TIMAP was a positive predictor (P = 0.045). Elevated P16 expression is found in more than half of the patients' specimens. DFS is negatively affected by younger age and the combined effect of smoking and P16 overexpression. TIMAP is overexpressed in P16-positive oropharyngeal cancer, and it is a favorable predictor of DFS.

In some cases of human epidermal growth factor 2 (HER2)-negative breast cancer, including triple-negative breast cancer, HER2 expression is sporadically and strongly upregulated, a condition known as HER2 heterogeneity. We investigated the clinicopathological features of patients with HER2 heterogeneity in triple-negative breast cancers treated with neoadjuvant chemotherapy. Thirty-nine patients with triple-negative breast cancer who had undergone preoperative chemotherapy participated in this study. To assess for HER2 heterogeneity, we used dual in situ hybridization slides. We evaluated the association between HER2 heterogeneity and clinicopathological factors such as rates of pathologic complete response (pCR) and of recurrence-free survival. Of the 39 patients, 15 (38.5%) had cancers with HER2 heterogeneity. The pCR rates were 13.3% among patients with HER2 heterogeneity and 20.8% among those with HER2 nonheterogeneity, but the difference was not significant. The recurrence-free survival rate was significantly lower in patients with HER2 heterogeneity than in those without (P = 0.025). HER2 heterogeneity is a significant predictor of poor prognosis in patients with triple-negative breast cancer treated with neoadjuvant chemotherapy.

We report a case of alpha-fetoprotein-producing endometrioid carcinoma (AFP-EC) that originated within an adenomyoma of the uterine corpus. A 76-year-old Japanese woman was incidentally discovered to have a uterine tumor along with multiple lung nodules. Upon surgical removal of the uterus, it was revealed that the tumor was situated within the adenomyoma. The tumor exhibited microfollicular structures and solid growth patterns, with hyaline globules, clear cell glands, and primitive tumor cells. Immunohistochemical analysis indicated the presence of germ cell markers, including AFP, SALL4, and glypican3, leading to final diagnosis of AFP-EC. Histopathologically, AFP-ECs exhibit characteristics similar to those of AFP-producing neoplasms in other organs. Furthermore, a nomenclature issue arises when distinguishing AFP-ECs from yolk sac tumors of the endometrium in older patients due to their shared features. The concept of retrodifferentiation or neometaplasia suggests that “endometrioid carcinoma with yolk sac tumor differentiation” or “endometrioid carcinoma with a primitive phenotype” may serve as more fitting terms for the diverse spectrum of AFP-producing neoplasms in the endometrium. In conclusion, this case underscores the diagnostic challenges posed by AFP-ECs arising from adenomyomas and emphasizes the need for refining the nomenclature and classification of AFP-producing neoplasms within the endometrium.

Chromobox (CBX)2 and CBX7, members of CBX family protein, show diverse expression patterns and contrasting roles in certain cancers. We aimed to investigate the subcellular expression patterns and clinical significances of CBXs in breast cancer (BC) subtypes, which have heterogeneous clinical course and therapeutic responses. Among the subtypes, the triple-negative BC (TNBC) is a heterogeneous group that lacks specific markers. We categorized TNBC into quadruple-negative BC (QNBC) and TNBC, based on androgen receptor (AR) status, to make the groups more homogeneous. Immunohistochemistry for CBX proteins was performed on 323 primary invasive BC tissues and their clinical significances were analyzed. Cytoplasmic CBX2 (CBX2-c) was linked to adverse clinicopathological factors and TNBC and QNBC subtypes. In contrast, nuclear CBX7 (CBX7-n) was associated with favorable parameters and luminal A subtype. CBX2-c expression increased progressively from that in benign lesions to that in in situ carcinomas and invasive cancers, whereas CBX7-n and AR expressions showed sequential downregulation. AR was lower in metastatic tissues compared to matched primary cancer tissues. We speculate that the upregulation of CBX2-c and downregulation of CBX7-n could play a role in breast oncogenesis and an adverse clinical course, suggesting them as potential prognostic markers and therapeutic targets in invasive BCs.

Serpinb9 is an inhibitor of granzyme B and is potentially involved in the immune escape of tumor cells. In the present study, bioinformatics analysis using open databases suggested that SerpinB9 is overexpressed in testicular embryonal carcinoma. Immunohistological analysis was performed on 28 cases of testicular germ cell tumors to investigate the relationship between SerpinB9 expression in testicular germ cell tumors and the tumor immune environment. SerpinB9 was significantly upregulated in the non-seminoma group and inversely correlated with the number of tumor-infiltrating CD8-positive cells. In addition, yolk sac tumors were characterized by the loss of human leukocyte antigen-class I expression. These findings suggest that SerpinB9 contributes to the immune escape of testicular germ cell tumors. Targeting therapy for SerpinB9 might therefore be useful in immunotherapy for testicular germ cell tumors resistant to immune checkpoint inhibitors.

The objective of this study was to establish an animal model of arteriosclerosis for assessing vasospasm and to investigate the relationship between arteriosclerosis and vasospasm. Twelve-week-old male Sprague-Dawley rats were fed a diet supplemented with adenine and vitamin D (adenine/vitD). Body weight, blood, and femoral artery histopathology were assessed at 2, 4, and 6 weeks. Change in the femoral artery was examined by transmission electron microscope (TEM). Vasospasm was induced by administering epinephrine extravascularly into the femoral artery and released by the treatment with lidocaine as a vasodilator. During this period, the extravascular diameter and blood flow were measured. The rats in the adenine/vitD group developed renal dysfunction, uremia, hyperphosphatemia, and elevated serum alkaline phosphatase. Histological and TEM analyses of the femoral arteries in the treated rats revealed the degeneration of elastic fibers and extensive calcification of the tunica media and intima. Vascular smooth muscles were degenerated and osteoblasts were developed, resulting in calcified arteriosclerosis. Vasospasm in arteriosclerotic arteries was detected; however, vasodilation as well as an increase in the blood flow was not observed. This study revealed the development of vasospasm in the femoral arteries of the arteriosclerotic rats and, a conventional vasodilator did not release the vasospasm.

The relationship between the expression of the SATB2 and CDX2 proteins and common molecular changes and clinical prognosis in colorectal cancer (CRC) still needs further clarification. We collected 1180 cases of CRC and explored the association between the expression of SATB2 and CDX2 and clinicopathological characteristics, molecular alterations, and overall survival of CRC using whole-slide immunohistochemistry. Our results showed that negative expression of SATB2 and CDX2 was more common in MMR-protein-deficient CRC than in MMR-protein-proficient CRC (15.8% vs. 6.0%, P = 0.001; 14.5% vs. 4.0%, P = 0.000, respectively). Negative expression of SATB2 and CDX2 was more common in BRAF-mutant CRC than in BRAF wild-type CRC (17.2% vs. 6.1%, P = 0.003; 13.8% vs. 4. 2%; P = 0.004, respectively). There was no relationship between SATB2 and/or CDX2 negative expression and KRAS, NRAS, and PIK3CA mutations. The lack of expression of SATB2 and CDX2 was associated with poor histopathological features of CRC. In multivariate analysis, negative expression of SATB2 (P = 0.030), negative expression of CDX2 (P = 0.043) and late clinical stage (P = 0.000) were associated with decreased overall survival of CRC. In conclusion, the lack of SATB2 and CDX2 expression in CRC was associated with MMR protein deficiency and BRAF mutation, but not with KRAS, NRAS and PIK3CA mutation. SATB2 and CDX2 are prognostic biomarkers in patients with CRC.

Early diagnosis is essential for the safer perinatal management of placenta accreta spectrum (PAS). We used transcriptome analysis to investigate diagnostic maternal serum biomarkers and the mechanisms of PAS development. We analyzed eight formalin-fixed paraffin-embedded placental specimens from two placenta increta and three placenta percreta cases who underwent cesarean hysterectomy at Sapporo Medical University Hospital between 2013 and 2019. Invaded placental regions were isolated from the uterine myometrium and RNA was extracted. The transcriptome difference between normal placenta and PAS was analyzed by microarray analysis. The PAS group showed markedly decreased expression of placenta-specific genes such as LGALS13 and the pregnancy-specific beta-1-glycoprotein (PSG) family. Term enrichment analysis revealed changes in genes related to cellular protein catabolic process, female pregnancy, autophagy, and metabolism of lipids. From the highly dysregulated genes in the PAS group, we investigated the expression of PSG family members, which are secreted into the intervillous space and can be detected in maternal serum from the early stage of pregnancy. The gene expression level of PSG6 in particular was progressively decreased from placenta increta to percreta. The PSG family, especially PSG6, is a potential biomarker for PAS diagnosis.

Cancer cell proliferation is affected by post-translational modifications of tubulin. Especially, overexpression or depletion of enzymes for modifications on the tubulin C-terminal region perturbs dynamic instability of the spindle body. Those modifications include processing of C-terminal amino acids of α-tubulin; detyrosination, and a removal of penultimate glutamic acid (Δ2). We previously found a further removal of the third last glutamic acid, which generates so-called Δ3-tubulin. The effects of Δ3-tubulin on spindle integrities and cell proliferation remain to be elucidated. In this study, we investigated the impacts of forced expression of Δ3-tubulin on the structure of spindle bodies and cell division in a pancreatic cancer cell line, PANC-1. Overexpression of HA-tagged Δ3-tubulin impaired the morphology and orientation of spindle bodies during cell division in PANC-1 cells. In particular, spindle bending was most significantly increased. Expression of EGFP-tagged Δ3-tubulin driven by the endogenous promoter of human TUBA1B also deformed and misoriented spindle bodies. Spindle bending and condensation defects were significantly observed by EGFP-Δ3-tubulin expression. Furthermore, EGFP-Δ3-tubulin expression increased the nuclear size in a dose-dependent manner of EGFP-Δ3-tubulin expression. The expression of EGFP-Δ3-tubulin tended to slow down cell proliferation. Taken together, our results demonstrate that Δ3-tubulin affects the spindle integrity and cell division.