Immunohistochemical investigation of CD34 antigen in male breast carcinoma.

A total of 30 archival cases of male breast carcinoma were studied immunohistochemically for the expression of CD34 antigen. An obvious CD34 staining was found in three cases. By adding the original CD34-positive case, recently published as unique CD34-stained male breast carcinoma, the number of positive cases comes to four. This case was classified as an invasive papillary carcinoma of solid conformation, whereas the three other cases were invasive ductal carcinomas, not otherwise specified. The aim of this study is to establish whether the CD34 positivity, observed in the case of papillary subtype, was a case-specific finding. CD34 expression in the male breast carcinoma, according to our findings, seems to be neither a feature presented exclusively by a singular case nor a specific immunophenotype characterising a special type. The presence or preservation of CD34 antigen in four totally male breast carcinomas may be considered as a novel finding that supports a relationship between these tumours and the progenitor CD34-positive stem cells, committed to the organogenesis of mammary gland. In this context we hypothesise an origin of male breast carcinoma from the stem cells expressing or not the CD34 antigen according to their stage of differentiation.

Comparative study of CD34, alpha-SMA and h-caldesmon expression in the stroma of gynaecomastia and male breast carcinoma.

AIMS: To address the fibroblastic/myofibroblastic nature of stroma in gynaecomastia and in male breast carcinoma, the expression of CD34, alpha-smooth muscle actin (SMA) and h-caldesmon in the stromal cells was investigated by immunohistochemistry. METHODS AND RESULTS: Representative archival paraffin blocks were collected from male patients with gynaecomastia (32 cases) and mammary carcinoma (24 cases) between 1984 and 2004 and CD34, alpha-SMA and h-caldesmon were assessed immunohistochemically using a streptavidin-biotin method. Thirty cases of gynaecomastia showed a CD34+, alpha-SMA- and h-caldesmon- immunophenotype with different CD34 staining intensity in the various histological subtypes. Positivity for alpha-SMA and negativity for CD34 and h-caldesmon was found in a case of florid gynaecomastia relating to reactive fibrosis due to previous surgical intervention. Acquisition of alpha-SMA expression by stromal fibroblasts but absence of CD34 staining was identified in 22 cases of male breast carcinoma. CONCLUSIONS: The immunophenotype of periductal connective tissue stroma in gynaecomastia appears to parallel the phenotype of normal breast stroma. In male breast carcinoma the stromal cell immunophenotype is similar to that of its female counterpart showing myofibroblastic differentiation. However alpha-SMA+ and CD34- are not specific to malignancy because such findings are also encountered in reactive fibrosis.

Angiogenesis in invasive breast carcinoma: is it associated with parameters of prognostic significance?

Recent experimental and clinical studies suggest that tumour-induced angiogenesis may be an important step in the evolution of malignant tumours, and may be related to prognosis. In our study we examined 42 cases of breast carcinoma (mean age: 56.76 +/- 13.5), 21 with lymph node metastases and 21 without. Angiogenesis was evaluated after immunohistochemical staining of tumour vessels, using polyclonal antibody to factor VIII related antigen (VIIIR-Ag) and counting of the three most active areas of neovascularization. In the same manner we counted the microvessels in lymph node metastases. The mean vessel count of node-negative cases (51.16 +/- 19.32) did not differ significantly from node-positive cases (45.66 +/- 17.44). In contrast patients younger than 50 years had much higher mean vessel counts (54.04 +/- 16.47) than did patients older than 70 years (38.03 +/- 16.73) producing a P value of < or = 0.05. No association was found between tumour size and mean vessel count, nor was there any significant difference between grade I (45.94 +/- 16.54), grade II (53.13 +/- 23.22) and grade III tumours (51.71 +/- 20.64). When we compared the mean vessel count of primary tumours with those of node metastases, we found much lower counts in the latter (P < or = 0.01). The differences in our results from previous studies, probably reflect the heterogeneity which exists between different tumours in their ability to induce angiogenesis. Additionally, there is some evidence in our study that angiogenesis is possibly related to patient age and probably depends on differences in the tumour stroma.

Reduction of CyA nephrotoxicity by nifedipine during and after experimental in situ renal preservation.

In order to evaluate the role of nifedipine in the nephrotoxic effect induced by both ischemia and CyA, 18 healthy mongrel dogs were used. The kidneys were exposed and subjected to 1 h of ischemia by clamping both renal vessels. To the renal artery of the first group of kidneys (n = 9), 300 mL of cold Euro-Collins solution, in which nifedipine (Bay a 1040-10 mg) was diluted, was infused for 15 min (nifedipine group), while 300 mL of cold Euro-Collins solution plus 10 mg of placebo (Bay a 1040-placebo) was infused to the renal artery of the second group (n = 9) of kidneys (placebo group). Venous drainage was effected through a plastic cannula. All animals received through a nasogastric catheter 20 mg/kg cyclosporine A at the beginning of the ischemia. The 1 h of ischemia was divided in a 15-min period of cold ischemia and 45-min of warm ischemia, at the end of which the clamps were removed. During the 2 h (30 min x 4) after reperfusion, 10 mg of nifedipine and placebo was administered additionally by a peripheral vein to the nifedipine and the placebo group, respectively. Then the kidneys were removed for histological study. Urine volume and creatinine and urea clearances of the nifedipine group were significantly higher than the placebo group (p < 0.001) while TxB2 levels were higher in the placebo group in all studied periods (p < 0.001). Urine sodium, FENa, osmolar clearance, and LDH values were significantly different (p < 0.01), but the urine potassium concentration was not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute cyclosporin A renal dysfunction in dogs reversed by calcium antagonists and antiplatelet agents.

The aim of this study was to assess the effect of nifedipine and piracetam alone or in combination in the protection of renal function and morphology after cyclosporin A (CyA) administration. Thirty healthy mongrel dogs with a mean body weight of 15 kg were sacrificed. Six animals (group C) were given CyA 20 mg/kg body weight per os, while the remaining groups (8 animals each) were given concomitantly 20 mg nifedipine (group CN) or 4 g of piracetam (group CP), or both drugs in combination (group CNP). After 5 days of drug administration the animals were anesthetized, both kidneys were exposed, and functional tests were performed. Then the kidneys were removed for histological study. The mean plasma CyA levels in the four groups were 1765 +/- 685 ng/mL, 1300 +/- 324 ng/mL, 1116 +/- 491 ng/mL and 1600 +/- 290 ng/mL, respectively. Urine volume, creatinine, urea, and osmolar clearances were significantly higher in the groups CN, CP, and CNP compared to the control group C (p < 0.01). Urine sodium concentration was significantly higher (p < 0.05 or p < 0.01) in nifedipine groups than in the other two groups of animals, while the fractional excretion of sodium (FENa%) was significantly higher (p < 0.01) in all treated groups compared to controls. Plasma thromboxane-B2 levels were significantly reduced by each drug alone or in combination (p < 0.01). Morphological lesions, similar in all groups, did not correlate with the functional improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of prostaglandin E2 (PGE2) in the prevention of acute renal failure in anesthetized dogs. In situ renal preservation.

Six healthy dogs, after control measurements, were subjected to renal artery occlusion for 90 min, under general anesthesia. 5 mg of PGE2 (Prostin E2, Upjohn) diluted in 100 mL of normal saline was infused directly into the left renal artery for 90 min (PG group), while only normal saline was infused into the right renal artery (control group). After removal of the clamps blood and urine samples were collected every hour for the first 3 h of revascularization and both kidneys were then removed for histological study by light microscopy. PG kidneys regained urine flow above the oliguric levels within 3 hr of revascularization (0.30 +/- 0.04 mL/min vs 0.14 +/- 0.03 mL/min in controls (p less than 0.001). Creatinine, urea, and osmolar clearances were also significantly higher in PG group (p less than 0.01 or p less than 0.001 for 2 and 3 hr of follow-up after revascularization). Urine sodium concentration and fractional sodium excretion (FENa) (%) were not significantly lower in the PG group compared to the controls. Histology showed focal brushborder loss, hyaline and granular casts, focal tubular dilation, and focal necrotic lesions on the tubular cells in both groups of kidneys. A direct cytoprotective effect of the PGE2 was not found. It is suggested that PGE2 is effective in the protection of renal function when it is administered during the mechanical occlusion model of acute renal failure in anesthetized dogs.

Effect of nifedipine in the protection of renal function during in situ preservation.

In an experimental study on six healthy dogs both kidneys were exposed and subjected to 1 h of ischaemia by clamping both renal vessels. To the left renal artery, 300 ml of cold (4 degrees C) Euro-Collins solution in which nifedipine (Bay a 1040--20 micrograms/kg per min) was diluted, was infused for 15 min. Simultaneously 300 ml of cold Euro-Collins solution plus 20 micrograms/kg per min of placebo (Bay a 1040--placebo) was infused in the right renal artery. The 1 h of ischaemia was divided in a 15-min period of cold ischaemia and 45 min of warm ischaemia, at the end of which both clamps were removed. During the 2 h (4 X 30 min) following the removal of the clamps, urine volume, urea and creatinine clearances, urine sodium concentration, sodium fractional excretion (%) and urine/plasma osmolality ratio measurements were made and results compared to the pre-ischaemia values. Both kidneys were then removed for histological study. The nifedipine group restored diuresis of 0.43 +/- 0.23 ml/min within 30 min, while this degree of diuresis (0.64 +/- 0.16 ml/min) was achieved by the placebo group at 120 min. Urine volume as well as creatinine and urea clearances of the nifedipine group were significantly higher in all studied periods compared to the placebo group (P less than 0.01 or P less than 0.025). Urine sodium and FENa (%) were not different between the two groups, and urine/plasma osmolality ratio was above 1.1 in all studied periods for both groups. The microscopic study did not show any significant differences between the two groups. We conclude that nifedipine is effective in the protection of renal function when it is administered during experimental in situ preservation.

Effect of pregnancy on the natural course of preexistent glomerular disease.

The clinical course of pregnancies in 3 patients with well defined glomerular diseases is described. Two women who had moderate renal insufficiency (serum creatinine greater than or equal to 1.6 mg/dl) at conception had also a dramatic progress to end-stage renal disease during pregnancy which in one case resulted in fetal loss. Glomerular diseases were focal glomerular sclerosis and poststreptococcal glomerulonephritis respectively. One patient with membranoproliferative glomerulonephritis was not affected. It is concluded that pregnancy can change the natural course of preexistent glomerular disease in patients with impaired renal function.