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.     

Augmentation of cytotoxicity of tumor-infiltrating lymphocytes by biological response modifiers.

Lymphocyte infiltration into a tumor has been regarded as an expression of host immunity against cancer, but tumor-infiltrating lymphocytes (TIL) have little or no cytotoxicity. This study examined two different approaches to augment this low cytotoxicity. Firstly, biological response modifiers (OK-432, PSK) were injected into gastric cancer intralesionally. Intralesional injection of OK-432 or PSK significantly augmented the cytotoxicity of TIL. By the injection of OK-432, the ratio of OKT8-, Leu7-positive cells were increased in the TIL subset. In the second approach, TIL of gastric or pulmonary cancer patients were cultured with interleukin-2 (IL-2) in vitro. Co-culturing with IL-2 augmented the low cytotoxicity of TIL, and broad-reactive lymphokine-activated killer (LAK) cells were generated from TIL.     

Carbohydrate metabolism of rats with biliary obstruction

Carbohydrate metabolism of rats with obstructive jaundice caused by bile duct ligation was studied by intravenous glucose tolerance test (IVGTT) and by liver perfusion. The altered levels of carbohydrate-metabolizing enzyme were examined in relation to the glucose metabolism of the cholestatic rats. In the IVGTT, the rate of fractional glucose removal was increased with increases in plasma insulin and glucagon and with a decrease in non-esterified fatty acid. In liver perfusion, neither the glucose uptake nor insulin extraction by the whole liver of icteric rats was different from the control. The increased rate of glucose removal in IVGTT may be due to enhanced glucose utilization by peripheral tissues resulting from hypersecretion of insulin. In liver perfusate supplemented with glucose, a decrease in the glucose uptake per unit liver weight was observed in relation to the lowered glucokinase activity. Formation of glycogen from glucose and of glucose from lactate was also impaired, indicating inhibition of the gluconeogenic system or relative hyperfunction of the glycolytic system, which may further contribute to the reduction in glycogen content. These metabolic disorders correlated well with the changes in activities of key carbohydrate-metabolizing enzymes, which showed a characteristic pattern consistent with the loss of differentiated hepatic functions. Uptake of glucose and its conversion to glycogen were reduced in the cholestatic liver in close association with altered activities of some of related enzymes. However, due to increased utilization by the peripheral tissues, the total amount of glucose utilized in the whole rat was not reduced.     

Modifying effects of 1'-acetoxychavicol acetate (ACA) and the novel synthetic retinoids Re-80, Am-580 and Am-55P in a two-stage carcinogenesis model in female rats

Effects of dietary administration of 1'-acetoxychavicol acetate (ACA) and the novel synthetic retinoids 4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (Re-80); 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid (Am-580); and 6-[(3,5-di-tert-butylphenyl) carbamoyl]nicotinic acid (Am-55P) were examined using a two-stage rat carcinogenesis model. A total of 190 female SD rats was treated sequentially with 1,2-dimethylhydrazine (DMH, s.c.); 7,12-dimethylbenz(a)anthracene (DMBA, i.g.); and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN, in the drinking water) during the first three weeks (DDD-initiation), and an additional 60 rats received the vehicle alone (non-initiation). One week after the completion of the initiation period, they were divided into nine groups and administrated Re-80 (at dose levels of 1.0 or 0.4 ppm), Am-580 (20 or 4 ppm), Am-55P (20 ppm), ACA (100 ppm), all-trans-retinoic acid (10 or 2 ppm) or no supplement in the diet for 33 weeks, until survivors were euthanatized at week 37 weeks. After DDD-initiation, all-trans-retinoic acid at the high dose delayed the development of mammary tumors. The multiplicity of colon tumors in the group fed Am-55P and the incidences of nephroblastomas with ACA or Am-580 were decreased as compared with the control values, but the other chemicals had no modifying effects on tumor development in any organs. Thus, among ACA and the novel synthetic retinoids tested, only Am-55P showed a weak inhibitory effect on a neoplasm of general interest under the present experimental conditions.     

Development of the rat meninx: experimental study using bromodeoxyuridine

The development of the rat meninx from the viewpoint of cell proliferation was studied microscopically and immunohistochemically using bromodeoxyuridine (BUdR). A compact cell layer around the neural tube, the meninx primitiva, was observed in 12- and 13-day fetuses. A reticular structure resembling the subarachnoid space appeared in the 14-day fetus. The ectomeninx, consisting of a collagen fiber layer, part of which became the dura mater, appeared in 15-day fetuses, allowing discrimination of the endomeninx, the arachnoid cell layer. The primordium of the choroid plexus also appeared in the lateral ventricle on the same day. Bone appeared in the primitive dura mater, and stratification of the meninx was almost complete in 21-day fetuses. BUdR-positive cells were confirmed in the meninx from day 12 of gestation to day 15 postpartum. The number of BUdR-positive cells was greatest in fetuses aged about 12 or 13 days, reaching nearly 50%, but decreased gradually toward the neonatal period. The findings of this study suggest that, after the migration of neural crest cells, marked cell proliferation in the meninx begins. Differentiation into various layers then follows and is almost complete before birth, whereas the proliferation of arachnoid cells continues even in the early neonatal period.