Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.     

Frozen-section services by telepathology: Experience of 100 cases in the San-in District, Japan

The early experience is reported here of the use of Intra-operative frozen-section service by telepathology using the Integrated Service Digital Network (ISDN), a commercially available system that is being connected between the Department of Pathology of Tottori University and Matsue City Hospital, a distance of 30 km. The transfer rate is currently 64kbit/s. The frozen-section service was conducted for a total of 117 tissue specimens (organs) from 100 patients between August 1993 and May 1995. The average time taken for examination of each specimen of frozen section was 13min, ranging between 2 and 42min. The average number of transmitted Images was 6.2. Six cases necessitated more than 11 transmitted Images to make a diagnosis, while 13 cases could be diagnosed from two images only. Correct and permissible diagnoses were obtained in 109 (93.2%) out of 117 specimens when comparing the telepathology diagnosis with that of direct microscopy. Improper or misdiag-nosis was made for eight cases (specimens), which were misinterpreted as papillary carcinoma in Basedow's disease, adenoma and hyperplasia in two pheochromocytomas, solid-tubular carcinoma in phyilodes tumor, mastopathy in invasive carcinoma, metastatic carcinoma in astrocytoma, follicular lymphoma in reactive hyperplasia, and lymphadenitis in follicular lymphoma. in retrospect, diagnosis of these cases should have been deferred. From the results, it was concluded that the Intraoperatlve frozen-section service by telepathology may be a worthwhile substitute for hospitals with limited accessibility to local pathology service, in spite of pitfalls in some cases. Well prepared, high-quality frozen sections, sufficient verbal communication with surgeons, and a rather conservative attitude on the part of a well-trained pathologist seem to be the essential Ingredients for reaching an accurate decision when using telepathology.     

Immunoglobulin G from anti-glucose-6-phosphate isomerase antibodies positive patient with rheumatoid arthritis induces synovitis in cynomolgus monkeys

Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) solely induce arthritis in mice. High titers of anti-GPI Abs are found in some patients with rheumatoid arthritis (RA), but their pathogenic role remains elusive. The aim of this study was to evaluate the pathogenic role of anti-GPI Abs in cynomolgus monkeys. IgG fractions were separated from sera of anti-GPI Abs-positive RA patients and healthy subjects and directly injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. At day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from monkey joints. In monkey joints, IgG including anti-GPI Abs resulted in recruitment of granulocytes and mononuclear cells, strong deposition of human IgG on the articular surface, and overexpression of C5aR, but no joint swelling. No infiltrated cells or IgG deposition were observed in monkeys injected with IgGs from healthy subjects. Our results suggest that IgG fraction from RA patients including anti-GPI Abs may play a crucial role in the generation of synovitis in monkeys, although the pathogenesis of anti-GPI Abs in RA patients is still uncertain.     

Detection rates of TT virus among children who visited a general hospital in Japan

Recently, genomic DNA of the novel TT virus (TTV) was isolated from patients suffering from posttransfusion hepatitis of unknown etiology. We examined sera from 197 children who visited the Department of Pediatrics at Toyohashi National Hospital. Sera were tested for TTV DNA by seminested polymerase chain reaction (PCR) using a set of primers synthesized according to the published TTV sequence. Ten children were found to be positive for TTV (5.1%). All positive PCR products were directly sequenced in both directions using a fluorescent dye terminator cycle sequencing system. The sequences were compared by a multiple sequence alignment and a phylogenetic tree was constructed. The phylogenetic tree showed that two of the TTV isolates found in the present experiment did not belong to any of the phylogenetic groups previously reported.     

Immunohistochemical localization of transforming growth factor alpha in chemically induced rat hepatocellular carcinomas with reference to differentiation and proliferation

Hepatocellular carcinomas (HCCs) were induced in male Fischer 344 rats with dietary 3'-methyl-4-(dimethylamino)-azobenzene treatment and were classified into solid, glandular (well- or poorly differentiated), and trabecular types. Investigation of cell proliferation kinetics and immunohistochemical localization of transforming growth factor alpha (TGF-alpha) demonstrated all solid (n = 24) and poorly differentiated glandular type (n = 6) HCCs to have TGF-alpha-positive nuclei. Nuclear staining of TGF-alpha was also observed in 13 of 28 (46%) trabecular-type HCCs, whereas 12 (43%) exhibited cytoplasmic staining, and 3 (11%) were negative. As for well-differentiated glandular HCCs, 7 of 20 (35%) were positively stained in their nucleus, another 7 (35%) demonstrated antibody binding in the cytoplasm, and 6 (30%) were negative. The order for growth rate evaluated by bromodeoxyuridine (BrdU) labeling was solid (38.22%), poorly differentiated glandular (26.82%), trabecular (7.98%), and well-differentiated glandular (2.57%) types. For trabecular HCCs with nuclear, cytoplasmic, or negative TGF reactions, values were 13.39% (n = 13), 3.61% (n = 12), and 2.01% (n = 3), respectively. Likewise, BrdU-labeling indices for the counterpart groups of well-differentiated glandular type HCCs were 4.53, 1.91, and 1.29%, respectively. The results indicate that TGF-alpha expression might be linked to histopathological differentiation and cell proliferation in rat HCCs.     

Supplementation Effect of Early Pregnancy Factor-Positive Serum into Bovine In Vitro Fertilization Culture Medium

PROBLEM: Early pregnancy factor (EPF) has been detected in pregnant bovine serum, and its activity appeared from 24 to 48 hr after insemination. However, in bovine in vitro fertilization (IVF), an EPF-like substance(s) had been detected in the culture medium of fertilized ovum. Therefore, we think that EPF and EPF-like substance(s) are very important materials for the development of the embryo. In this study, we examined the development of the embryo when fertilized bovine ova were cultured with IVF culture medium supplemented with EPF-positive or -negative serum. METHOD OF STUDY: EPF activity of each serum (fetal calf serum [FCS], calf serum [CS], estrus bovine serum, and pregnant bovine serum) was assessed by the bovine-rosette inhibition test. The sera were supplemented in TCM-199 culture medium, and IVF bovine ova were cultured with the media for 6 or 7 days, respectively. The culture media of each group were evaluated for EPF activity by the bovine-rosette inhibition test 48 hr after IVF. The cleavage rate of each group was calculated at 48 hr, and 6 or 7 days after IVF. The culture medium of cumulus cells was also tested for EPF activity. RESULTS: Only the pregnant bovine sera were EPF positive. All the culture media 48 hr after IVF became EPF positive. Additionally, the culture medium of cumulus cells did not have EPF activity. There was no significant difference in the cleavage rate of the EPF-positive and - negative sera 48 hr after IVF. However, the cleavage rate of EPF-positive sera tended to be higher than the negative sera. In contrast, the blastocyst development rates of EPF-positive sera were significantly higher than those of the negative sera 6 to 7 days after IVF (P < 0.05). CONCLUSIONS: The data suggest that an EPF-like substance(s) may be secreted from the in vitro fertilized bovine ovum but not from the cumulus cell, and that the EPF in the pregnant serum may accelerate the development of the bovine embryo in IVF.     

Calcineurin in the postnatal striatum of the rat: an immunohistochemical study

Summary This report concerns the postnatal expression of calcineurin (CaN) in rat striatum. For this purpose an immunohistochemical procedure was used. In neonatal striatum CaN immunoreactivity was found in discrete patches composed of many immature cells. With development there was an increase in staining intensity and in the proportion of positively reacting cells. CaN expression and localization in the striatum of 22–25 day old rats were similar to those of adult animals.     

Constitutive production of interleukin 6/B cell stimulatory factor-2 from inflammatory synovium

Interleukin 6 (IL-6) production from synovial tissues of various diseases was examined. Augmented IL-6 production was found in inflammatory synovium not only in RA but also in other kinds of synovitis, including psoriatic arthritis and Beh?et's disease. Increased amounts of IL-6-mRNA were detected in rheumatoid synovium using a dot blot hydridization technique. Furthermore, there was a positive correlation between IL-6 production and accumulation of plasma cells in the synovium. These findings suggest that IL-6 plays an important role not only in immune response but also in active inflammation in various kinds of synovitis.     

The inhibitory effects of isoflavonoids and resveratrol on oxdized low-density lipoprotein uptake in macrophage cell line J774.1

The interaction between oxidized low-density lipoprotein (LDL) and macrophages are known to be important in the development of arteriosclerosis. Macrophages take up oxidized LDL, becoming foam cells, which contribute to the thickening of the blood vessel wall. The antioxidant properties of polyphenols found in vegetables and other foods have been shown to have a protective effect against arteriosclerosis. To elucidate the effect of flavonoids from fruits, vegetables and cereals on oxidized LDL uptake in macrophages, the inhibitory activity of various flavonoids on DiI-ac-LDL uptake reaction in mouse macrophage cell line J774.1 was measured. We found significant uptake of DiI-ac-LDL, but not DiI-LDL, into the J774.1 cells. In addition, polyinosin and dextran sulphate inhibited uptake, but apigenin, kaempferol, and naringenin, did not. Isoflavones and resveratrol significantly inhibit uptake of DiI-ac-LDL into macrophages, and have a protective effect against arteriosclerosis.