Cdc20 and securin overexpression predict short-term breast cancer survival.

BACKGROUND: Cdc20 is an essential component of cell division and responsible for anaphase initiation regulated by securin degradation. Cdc20 function is strongly regulated by the spindle assembly checkpoint to ensure the timely separation of sister chromatids and integrity of the genome. We present the first results on Cdc20 in a large clinical breast cancer material. METHODS: The study was based on 445 breast cancer patients with up to 20 years of follow-up (mean 10.0 years). DNA content was determined by image cytometry on cell imprints, and Cdc20 and securin immunohistochemistry on tissue microarrays of breast cancer tissue. RESULTS: In our results, high Cdc20 and securin expression was associated with aneuploid DNA content. In prognostic analyses, high Cdc20 immunoexpression alone and in combination with high securin immunoexpression indicated aggressive course of disease and up to 6.8-fold (P<0.001) risk of breast cancer death. Particularly, high Cdc20 and securin immunoexpression identified a patient subgroup with extremely short, on average 2.4 years, breast cancer survival and triple-negative breast cancer (TNBC) subtype. CONCLUSIONS: We report for the first time the association of high Cdc20 and securin immunoexpression with extremely poor outcome of breast cancer patients. Our experience indicates that Cdc20 and securin are promising candidates for clinical applications in breast cancer prognostication, especially in the challenging prognostic decisions of TNBC.

Immunohistochemical study of neuroendocrine cells at the gastric cardia mucosa.

BACKGROUND/AIMS: The gastric cardia mucosa is a narrow band of tissue between the oesophagus and the stomach. The physiological role of this tissue is unknown. This study examined the presence and characteristics of neuroendocrine cells at this site. METHODS: Biopsy samples were obtained from across normal appearing squamocolumnar junctions. The cardiac mucosa was defined as the presence of special type mucosa composed of mucous secreting glands in the immediate vicinity of oesophageal squamous epithelium. Biopsy specimens were stained with haematoxylin and eosin, alcian blue (pH 2.5) periodic acid Schiff, and modified Giemsa. The chromogranin A and Fontana-Masson stains were used to identify neuroendocrine cells, which were also stained immunohistochemically for gastrin, serotonin, glucagon, pancreatic polypeptide, somatostatin, and vasoactive intestinal peptide. RESULTS: Chromogranin positive cells were seen in 18 cases with adequate biopsy specimens from the gastric cardia mucosa. These cells were all serotonin positive, but stains for other peptide hormones remained negative. Serotonin positive cells were detected only at the base of foveolae at the periphery of mucous secreting cardiac glands, giving a microscopic appearance resembling that of endocrine cells at the gastric antrum. The presence and numbers of serotonin positive cells did not correlate with chronic inflammation or intestinal metaplasia of the cardiac mucosa. These cells were seen both in Helicobacter pylori positive and negative patients. CONCLUSIONS: Serotonin positive cells appear to be the sole neuroendocrine cell type at the gastric cardia mucosa. These cells may have a role in regulating the physiology of the gastric cardia mucosa and the lower oesophageal sphincter.

Pulmonary adiaspiromycosis in a two year old girl.

A case of disseminated bilateral pulmonary adiaspiromycosis is reported in a two year old Finnish girl. She recovered from this rare infection after treatment with amphotericin B. She is the first human case of adiaspiromycosis in Scandinavia and she is the youngest child with this disease reported so far. Electron microscopy showed that the three layers of the spore wall were not typical; rather, there seemed to be a gradual transition between the main wall zones, which may be split into an indefinite number of thin layers. Varying numbers and thicknesses were seen with different staining methods, and in different spores. Diagnosis relies on recognition of the fungus in a pulmonary biopsy specimen, because there are no reliable serological tests and culture of the fungus is time consuming and not always successful. It was thought that this patient had become infected as a result of contact with soil dust containing the spores in the yard surrounding her home, and as a result of her mother's work in a large garden shop.

Ultrastructural aspects of liver injury with special reference to small bile ducts in patients with ulcerative colitis.

Liver tissue specimens taken at colectomy from 29 patients with chronic ulcerative colitis were studied by electron microscope. The fine-structural alterations were correlated with light microscopy and with biochemical liver function tests. The purpose was to identify ultrastructural features which could explain the pathogenesis of sclerosing cholangitis. Severely injured bile-duct epithelial cells were seen in three out of the eight light-microscopically diagnosed cholangitis cases, in the two cases of non-specific reactive hepatitis, and in the two fatty livers. Four cholangitis cases had, in heavily thickened bile-duct basement membranes, translucent areas containing bile-like material. Bile-duct microvilli were often blunted, and reduced in number. Intracanalicular bile thrombi and bile inclusions in hepatocytes were seldom seen, mostly but not exclusively in cholangitis. The fine-structural alterations apparently represent various stages of liver injury. These findings do not appear to be specific, but their prominence seems to correlate with the progression of the disease, at least in the case of histological parameters, but also in serum enzyme activities indicative of cholestasis. The bile-like electron-dense material found in proliferating basement membranes, very possibly regurgitated into the injured bile-duct wall after epithelial injury, could enhance the development of periductal fibrosis, leading to progression of sclerosing cholangitis.

Observations on the structure and the biomechanics of the cricothyroid articulation.

We examined quantitatively the ventrodorsal gliding occurring along a sagittal plane in the cricothyroid articulation. For this purpose we used 10 fresh excised human larynges taken at autopsy. Furthermore we examined the morphology, the hydroxyproline content and collagen types of the ligaments and the articular capsule of the cricothyroid articulation. This articulation appeared to be a synovial joint, supported by two ligaments: the lateral and posterior ceratocricoid ligament and articular capsule. The ligaments and the capsule contained both type I and type III collagen fibres and they were rich in elastin fibres 1-2.5 microns in diameter. Ventrodorsal gliding was generally possible when the joint was not rotated to its extremes. The marked individual variation was not essentially affected by sex or age. The collagen content of the lateral ceratocricoid ligament showed a statistically significant negative correlation with the gliding. The articular facet of the cricoid cartilage, which was not usually well-shaped, limits the gliding. A force of +/- 1.0 N caused on the average a change of +/- 1.0 mm in the length of the vocal cord. Further research is needed to evaluate the physiological importance of these findings.

Cerebral cortex slices in sodium-free medium: depletion of synaptic vesicles.

Rat cerebral cortex slices superfused for 5 min in sodium-free medium after 30-min stabilization and 25-min superfusion periods in sodium-containing medium displayed a well-preserved tissue structure and mostly intact neurons and glial cells. Electron-microscopic morphometry showed the number of presynaptic terminals containing few (less than or equal to 10) vesicles to increase 3-fold after the 5-min depletion of sodium. The 90-min sodium depletion resulted in increased swelling and an additional decrease in synaptic vesicles. The results show that from a morphological point of view the substitution of sodium by choline with brain slice techniques is an eminently suitable method for studies on synaptic neurochemistry.

Comparison of CA 19-9 and carcinoembryonic antigen (CEA) levels in the serum of patients with colorectal diseases.

The serum levels of CA 19-9 and carcinoembryonic antigen (CEA) were determined in 37 patients with benign colorectal diseases and in 111 patients with newly discovered colorectal carcinomas or clinically verified relapses. In cancer patients, the CA 19-9 level ranged from normal (0-37 U ml-1) to 77,500 U ml-1 whereas all samples but one from patients with benign colorectal diseases had a normal value. CA 19-9 was increased in 46% and 45% of patients with an advanced (Dukes C or D) carcinoma or a verified recidive, respectively. Only one out of 26 patients (4%) with a localized (Dukes A or B) carcinoma displayed an elevated CA 19-9 level (greater than 37 U ml-1). No clear correlation was found between the CA 19-9 and CEA levels. The sensitivity of the CA 19-9 test (36%) was poorer than that of the CEA assay (69%), but the new test was markedly more specific (97% vs 70%) than the CEA assay.

Fine-structural evidence for vascular injury in patients with interstitial cystitis.

Bladder vessel walls of 20 patients with interstitial cystitis were studied by the electron microscope. 14 (70%) had severe endothelial injury. 10 (50%) showed injured smooth muscle cells. Odd basement membrane proliferations and disruptions were seen. Clusters of microfibrils about 10 nm in diameter and numerous partially membrane-bound vesicles of 100-600 nm with granular or tiny vesicular content ("granulovesicular bodies") were also seen. Intercellular junctions of endothelial cells were open and there was emigration of polymorphonuclear leucocytes and platelets. The findings show pronounced vascular injury to have taken place, with neoformation of elastic tissue. It is suggested that the injury is immunologically mediated and that particularly those clusters of connective tissue microfibrils not yet covered by an amorphous elastin component may be involved in the pathogenesis of this disease.

Hyperkeratosis lenticularis perstans (Flegel's disease).

A 62-year-old female with a 20-year history of small horny papules on the skin of the legs is described. Light microscopy revealed a hyperkeratotic papule with atrophic epidermis and a dense dermal inflammatory cell infiltrate with many cerebriform lymphocytes not earlier described in connection with hyperkeratosis lenticularis perstans (HLP). The electron-microscopic picture showed membrane-coating granules (MCG) and keratohyalin located in different cells, indicating that the disorder of keratinization in HLP is possibly caused by reduced co-operation between these cells and that the keratinization process occurs in the absence of MCG. Perpetual treatment with oral retinoid was successful.

Macroglobulinemia with abdominal symptoms caused by intestinal extracellular macroglobulin.

A 54-year-old woman had a marked splenomegaly, diarrhoea and abdominal cramps. Her serum contained monoclonal IgM with lambda light chains, and lambda light chains were also excreted in the urine. Bone marrow and spleen punctures failed to reveal the classic morphological changes associated with Waldenström's macroglobulinemia. A peroral jejunal biopsy disclosed homogenous extracellular material consisting of IgM, lambda and kappa light chains were demonstrable in a large number of the plasma cells and plasmacytoid cells in post-mortem specimens of bone marrow, spleen and some lymph nodes by the peroxidase-anti-peroxidase techniques. The causes of the "discrepancy" between the serum findings and tissue findings are discussed.

Response of synovial immunocytes to intra-articular agents in experimental arthritis.

In rabbits with immune arthritis the numbers of lymphoid aggregates and pyroninophilic and non-pyroninophilic cells per unit area of synovium were calculated from sections taken at various intervals after intra-articular drug injections. A model of immune arthritis based on the results is presented. In the active phase of the arthritis, plasma cells, plasmablasts and lymphoid aggregates proliferate, while the number of lymphocytes decreases. In the inactive phase after treatment, the cell pattern is the reverse. The ratio of pyroninophilic to non-pyroninophilic cells proved to be a good measure of the activity of the arthritis. A favourable therapeutic effect was achieved with triamcinolone hexacetonide and combined steroid-osmic acid, but not with osmic acid alone.