Medical Molecular Morphology最新文献

Poorly differentiated adenosquamous carcinoma (glassy cell carcinoma) of the cervix is extremely rare, accounting for 1-2% of all cervical cancers. Herein, we report a case with coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), "usual-type" adenocarcinoma, and squamous cell carcinoma in situ of the cervix. A female patient in her 60 s was referred to our hospital and diagnosed with poorly differentiated adenosquamous carcinoma based on cervical cytology and biopsy. The tumor was classified as clinical stage IB1 cervical cancer following magnetic resonance imaging; radical hysterectomy was performed. Histopathological examination revealed poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ, all coexisting. All carcinoma regions showed identical sizes to high-risk human papillomavirus (HPV) in fragment analysis. The patient is currently alive, without evidence of recurrence, 31 months post surgery. In this case, three different carcinomas coexisted. Fragment analysis of the patient's HPV status suggested that all carcinomas were related to an infection with the same high-risk HPV type. To determine the precise mechanism of tumor development, i.e., whether the tumors were of the mixed or collision type, further studies are needed, including clonal analysis for the loss of heterozygosity pattern.

Breast papillary neoplasms include a wide range of tumor types, and their pathological diagnosis is sometimes difficult. Furthermore, the etiology of these lesions is still not fully understood. We report the case of a 72-years-old woman referred to our hospital with bloody discharge from the right nipple. An imaging study detected a cystic lesion, including a solid component contiguous with the mammary duct, in the subareolar region. The lesion was then removed by segmental mastectomy. Pathological examination of the resected specimen revealed an intraductal papilloma with atypical ductal hyperplasia. Moreover, the atypical ductal epithelial cells expressed neuroendocrine markers. The presence of an intraductal papillary lesion with neuroendocrine differentiation suggests solid papillary carcinoma. Thus, this case suggests that intraductal papilloma could be a precursor of solid papillary carcinoma.

The purpose of this study was to investigate whether fibroblast growth factor 4 (FGF4) and FGF9 are active in dentin differentiation. Dentin matrix protein 1 (Dmp1) -2A-Cre transgenic mice, which express the Cre-recombinase in Dmp1-expressing cells, were crossed with CAG-tdTomato mice as reporter mouse. The cell proliferation and tdTomato expressions were observed. The mesenchymal cell separated from neonatal molar tooth germ were cultured with or without FGF4, FGF9, and with or without their inhibitors ferulic acid and infigratinib (BGJ398) for 21 days. Their phenotypes were evaluated by cell count, flow cytometry, and real-time PCR. Immunohistochemistry for FGFR1, 2, and 3 expression and the expression of DMP1 were performed. FGF4 treatment of mesenchymal cells obtained promoted the expression of all odontoblast markers. FGF9 failed to enhance dentin sialophosphoprotein (Dspp) expression levels. Runt-related transcription factor 2 (Runx2) was upregulated until day 14 but was downregulated on day 21. Compared to Dmp1-negative cells, Dmp1-positive cells expressed higher levels of all odontoblast markers, except for Runx2. Simultaneous treatment with FGF4 and FGF9 had a synergistic effect on odontoblast differentiation, suggesting that they may play a role in odontoblast maturation.

Matrix metalloproteinases (MMPs) and their major source, endometrial stromal cells (ESCs), play important roles in menstruation. However, other mechanisms in endometrial shedding may be unexplored. This study focused on four proteins: S100A8 and S100A9 (alarmins) are binding partners and induce MMPs, MMP-3 cycle-dependently plays a key role in the proteolytic cascade, and CD147, which has S100A9 as its ligand, induces MMPs. Immunostaining for these proteins was performed on 118 resected specimens. The percentage and location of each positive reaction in ESCs were measured and compared using Image J. The influence of leukocytes on S100A8 or S100A9 immunopositivity was also examined. From the premenstrual phase, S100A8 and MMP-3 began to have overlapping expressions in ESCs of the superficial layer, and ESC detachment was found within these sites. S100A9 was expressed from the late secretory phase and CD147 already from earlier. Later, the expression sites of S100A9 and CD147 included those of S100A8. Before menstruation, S100A8 or S100A9 expression was not affected by leukocytes. These results suggest that the local formation of S100A8/S100A9 complex, which occurs specifically in ESCs upon progesterone withdrawal, induces the local expression of MMP-3 and serves as a switch to the lysis phase.

Accumulated evidence has shown that endocan, which was originally called endothelial cell-specific molecule-1, is an attractive prognostic factor in a variety of cancers. However, the relevance of endocan expression in human malignancies remains to be clarified. In the present study, the expression of endocan in cervical squamous neoplasia of the uterus, including low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), as well as in invasive squamous cell carcinoma was examined by immunohistochemistry. Endocan was not sufficiently expressed in the normal cervical epithelium. Endocan expression was present in LSIL cases but was limited to basal and parabasal areas of the cells. HSIL cases exhibited strong expression of endocan with widely distributed expression toward the epithelial surface. In contrast, further strong expression of endocan was not observed in patients with invasive carcinoma. This study is the first study showing increased expression of endocan in precancerous dysplastic lesions and malignancy of the cervix. The data suggest that a high expression level of endocan potentially contributes to the development of cervical squamous neoplasia of the uterus.

Adenomatous polyposis coli (APC) is recognized as an antioncogene related to familial adenomatous polyposis and colorectal cancers. However, APC is a large protein with multiple binding partners, indicating APC has diverse roles besides as a tumor suppressor. We have ever studied the roles of APC by using APC^1638T/1638T (APC1638T) mice. Through those studies, we have noticed stools of APC1638T mice were smaller than those of APC^+/+ mice and hypothesized there be a disturbance in fecal formation processes in APC1638T mice. The gut motility was morphologically analyzed by immunohistochemical staining of the Auerbach's plexus. Gut microbiota was analyzed by terminal restriction fragment length polymorphism (T-RFLP). IgA concentration in stools was determined by enzyme-linked immunosorbent assay (ELISA). As results, macroscopic findings suggestive of large intestinal dysmotility and microscopic findings of disorganization and inflammation of the plexus were obtained in APC1638T mice. An alteration of microbiota composition, especially increased Bacteroidetes population was observed. Increases in IgA positive cells and dendritic cells in the ileum with high fecal IgA concentration were also confirmed, suggesting over-activation of gut immunity. Our findings will contribute to our understanding of APC's functions in the gastrointestinal motility, and lead to a development of novel therapies for gut dysmotility-related diseases.

Hereditary hemochromatosis type 4 is an autosomal-dominant inherited disease characterized by a mutation in the SLC40A1 gene encoding ferroportin. This condition can be further subdivided into types 4A (loss-of-function mutations) and 4B (gain-of-function mutations). To date, only a few cases of type 4B cases have been reported, and the treatment has not been clearly mentioned. Here, we report a genotype of hereditary hemochromatosis type 4B involving the heterozygous mutation c.997 T > C (p. Tyr333His) in SLC40A1. The patient was treated with red blood cell apheresis every month for 1 year, followed by oral deferasirox, and the combined therapy was found to be effective.

To improve the resolution of low-vacuum scanning electron microscopy (LVSEM), the epoxy resin block for the transmission electron microscopy (TEM) was observed directly with LVSEM. After observing ultrathin sections from renal biopsies of IgA nephropathy, membranous nephropathy, lupus nephritis, diabetic nephropathy (DM), thin basement membrane disease (TBMD), Alport's syndrome, Fabry's disease, and renal amyloidosis, the epoxy resin blocks of the same sites were observed by LVSEM and compared. The LVSEM image of the epoxy resin block corresponds to the negative of the TEM image, and when the gradation is reversed, the LVSEM image was comparable to the TEM image. At a low magnification of 100 ×, the entire specimen, including the glomerulus, was obtained. LVSEM at 5000 × magnification was sufficient to identify paramesangial deposits in IgA nephropathy and subepithelial electron-dense deposits (EDD) and spikes in membranous nephropathy. Glomerular basement membrane thickening in DM and thinning in TBMD could be sufficiently diagnosed with LVSEM at 6000 ×. Accumulation of ceramide in Fabry's disease was easily identified, but amyloid fibril could not be identified by LVSEM. LVSEM of renal biopsy epoxy resin blocks can replace TEM up to moderate magnification.

This study aimed to demonstrate and compare the accuracy of tooth shade selection due to the remineralized enamel crystal with enamel matrix derivative (EMD) in vitro. Etched enamel slices were immersed in four types of mineralization buffers for 16 h. Sodium fluoride (NaF) was added to final concentrations of 1-100 ppm with the mineralization buffer that demonstrated the highest mineralization efficiency. EMD was added to the mineralization buffer containing NaF to see if it has any remineralization capacities. The remineralized enamel crystal was analyzed by SEM and XRD. The tooth shade was evaluated by CIE L*a*b*. The results showed that, without NaF, plate-like nanocrystals were formed on the enamel surface, but with NaF, needle-like nanocrystals were formed. By adding EMD, a layer of well-compacted hydroxyapatite crystals was successfully precipitated onto the natural enamel surface. No significant differences were observed in the L* value of the mineralization surface pre-etching and after mineralization buffer containing NaF and EMD. A new method has been developed to recover the color quality of enamel, as well as to mineralize the tooth enamel by constructing hydroxyapatite crystals with mineralization buffers containing NaF and EMD on the etched tooth surface.