Molecular profiles of non-small cell lung cancers in cigarette smoking and never-smoking patients.

PURPOSE: Molecular features of non-small cell lung cancer (NSCLC) in never-smokers are not well recognized. We assessed the expression of genes potentially related to lung cancer etiology in smoking vs. never-smoking NSCLC patients. METHODS: We assayed frozen tumor samples from surgically resected 31 never-smoking and 54 clinically pair-matched smoking NSCLC patients, and from corresponding normal lung tissue from 27 and 43 patients, respectively. Expression of 21 genes, including cell membrane kinases, sex hormone receptors, transcription factors, growth factors and others was assessed by reverse transcription - quantitative PCR. RESULTS: Expression of 5 genes was significantly higher in tumors of non-smokers vs. smokers: CSF1R (p<0.0001), RRAD (p<0.0001), PR (p=0.0004), TGFBR2 (p=0.0027) and EPHB6 (p=0.0033). Expression of AKR1B10 (p<0.0001), CDKN2A (p<0.0001), CHRNA6 (p<0.0001), SOX9 (p<0.0001), survivin (p<0.0001) and ER2 (p=0.002) was significantly higher in tumors compared to normal lung tissue. Expression of AR (p<0.0001), EPHB6 (p<0.0001), PR (p<0.0001), TGFBR2 (p<0.0001), TGFBR3 (p<0.0001), ER1 (p=0.0006) and DLG1 (p=0.0016) was significantly lower in tumors than in normal lung tissue. Expression of IGF2 was higher in tumors than in healthy lung tissue in never-smokers (p=0.003), and expression of AHR (p<0.0001), CSF1R (p<0.0001) and RRAD (p<0.0001) was lower in tumors than in healthy lung tissue in smokers. CONCLUSION: Expression of several genes in NSCLC is strongly related to smoking history. Lower expression of PR and higher expression of ER2 in tumors suggests a possibility of hormonal therapeutic intervention in selected NSCLC patients. Distinct molecular features of NSCLC in never-smokers, e.g. CHRNA6 upregulation, may prompt new treatment strategies.

Does the septic shock interfere experimental acute pancreatitis in rats?

INTRODUCTION: Acute pancreatitis is a disease involving pro-inflammatory mediators. Two complex and multifactorial pathogenetic ways lead to edematous or necrotizing pancreatitis. The course of the disease is thought to be the consequence of an acute inflammatory response. AIM: The authors examined the impact of Escherichia coli LPS on the acute cerulein pancreatitis in rats. METHODS: The study was performed on rats using the ceruleine pancreatitis model. The activation status of polymorphonuclear cells, blood IL-6 concentration, oxidative stress parameters, pancreatic enzymes concentration and microscopic alterations were determined at 5th and 9th h observations. RESULTS: In acute pancreatitis and acute pancreatitis with LPS groups, the peripheral polymorphonuclear cells activity was lower than in control one. Authors noticed the same neutrophil activation in acute pancreatitis after lipopolysaccharide administration although the peripheral blood polymorphonuclear cells count was significantly higher at the 9th h observation. LPS neither changed the oxidative stress within pancreatic gland, nor amylase or serum lipase activity. LPS given to acute pancreatitis animals resulted in significant increase of serum IL-6 concentration at 5th observation turning normal after 9th h. CONCLUSIONS: Collected data supports thesis of early polymorphonuclear cells involvement in acute pancreatitis and oxidative stress evidence in pancreatic parenchyma. However, results did not reveal that administration of LPS amplified inflammatory response during the course of acute pancreatitis.

Nonalcoholic fatty liver disease treated by gastroplasty.

Nonalcoholic steatohepatitis (NASH), which is the most severe histologic form of nonalcoholic fatty liver disease (NAFLD), is emerging as the most common clinically important form of liver disease in obese patients. The prevalence of NASH may increase with the rise in the rate of obesity and metabolic syndrome in affluent communities. The aim of this work is to describe clinical and histopathologic findings and correlate liver tissue damage to the length of duration of the obesity in the group of patients who underwent surgery as obesity treatment. Eighty-seven severely or morbidly obese patients underwent gastroplasty. Each patient was evaluated with complete clinical and laboratory medical assessment together with wedge liver biopsy taken from 59 unselected patients during the surgery. Patients were followed up for 41 months. Repeat liver biopsy was taken from 10 patients. Pathologic analysis recorded the presence and degree of steatosis, portal and lobular inflammation and fibrosis. Age, body mass index (BMI), and laboratory assessment correlated with pathologic data. Male patients showed more pronounced metabolic syndrome and fatty liver damage. Patients who become obese in childhood or as teenagers showed no differences in metabolic syndrome and NAFLD in mature age. There was statistically significant association between BMA, elevated transaminases, NAFLD, and fibrosis. Significant weight reduction was observed within first year after surgery, was slower in the second year, and stabilized within third year. Remarkable improvement followed in biological markers of metabolic syndrome. Ninety-six percent of initial liver biopsies had steatosis; 16% developed steatohepatitis and mild perivenular fibrosis. Significant improvement of the degenerative and inflammatory hepatic lesions in repeated biopsies and liver function readings was noted within 8 months after surgery. Obesity is a major and independent risk factor for the metabolic syndrome, NAFLD, NASH, and fibrosis. Surgical treatment improves metabolic abnormalities and hepatic lesions in long-term observations.

Overexpression of cathepsin B correlates with angiogenesis in colon adenocarcinoma.

Some studies have shown the influence of proteases and vascular density in colorectal primary tumors on spreading and on the course of colorectal cancer. In the present study we have analyzed the relationships between overexpression of cathepsin B protein and angiogenesis intensity in resected colon tumors and their impact on prognosis. It has been investigated in a series of 90 colon cancer patients. Immunohistochemistry was used to evaluate cathepsin B overexpression in cancer cells and to visualize microvessels with antibodies against von Willebrand factor. Overexpression of cathepsin B was observed if more than 50% of cancer cells in searched field showed immunoreactivity with antibody against cathepsin B. Intensity of angiogenesis was evaluated as a mean number of microvessels from three fields with highest vessel number. In 36 cases (40%) overexpression of cathepsin B was detected. Increased angiogenesis (above median 31 vessels per 0.785 mm2) correlated positively with cathepsin B overexpression (p=0.0006). Higher vascular density associated with the presence of metastases in regional lymph nodes (p=0.01). Overexpression of cathepsin B was observed more often in group of older people (age above median 65 years; p=0.005). According to univariate analysis metastases in regional lymph nodes (p=0.0007), increased angiogenesis (p=0.0085), and distant metastases (p=0.02) were the features potentially influencing prognosis. Multivariate analysis revealed independent prognostic value only in case of metastases in regional lymph nodes (p=0.013) and when distant metastases were present (p=0.021), but not when increased angiogenesis in primary colon adenocarcinoma was observed (p=0.078). In conclusion we can say that there is a close relationship between intensity of angiogenesis and overexpression of cathepsin B protein in cancer cells in resected colon adenocarcinoma.

Peripheral primitive neuroectodermal tumor within the spinal epidural space.

A case of an epidural spinal peripheral primitive neuroectodermal tumor (pPNET) in a 13-year-old girl is presented. The tumor was disseminated at the moment of diagnosis, thus only diagnostic oligobiopsy of the epidural mass was performed. Histologically the tumor was composed of small round blue cells. The neoplastic cells expressed MIC2 and features of neural differentiation on immunohistochemical staining (neuron-specific enolase, synaptophysin and NCAM positivity). Fluorescent in situ hybridization (FISH) analysis was performed for the final diagnosis and the translocation t(11;22)(q24;q12) was detected. The present case emphasizes the usefulness of FISH in differential diagnosis of tumors, especially when only routinely fixed material is available.

Meningioangiomatosis with a predominant fibrocalcifying component.

A case of meningioangiomatosis, resected from the parietal lobe in a 31-year-old female is presented. Macroscopically, the lesion was composed of five calcified nodules embedded within hardened elastic tissue. Histologically, cortical and subcortical calcified masses were found surrounded by a palisade of spindle and/or oval cells. In adjacent nervous tissue many pathological microvessels were observed and some were ensheathed by a perivascular proliferation of spindle cells. Moreover, gliosis with Rosenthal fibers and prominent connective tissue elements were observed. Immunohistochemical analysis based on monoclonal antibodies was performed. The spindle cells both within the palisades and the perivascular proliferations were vimentin and usually epithelial membrane antigenpositive. The possible pathogenesis of meningioangiomatosis is discussed and the role of angiogenesis within this lesion emphasized.

Vasculopathy and amyloid beta reactivity in brains of patients with acquired immune deficiency (AIDS).

The authors examined multiple brain sections from 15 autopsy cases of AIDS for the vascular changes, presence of amyloid plaques and signs of axonal damage. The mean patients age was 33.8 years (range 24-48 years). Neuropathological findings included: HIV-specific changes (5), opportunistic infections (7), lymphoma (1) and two cases with nonspecific changes. All sections were stained with hematoxylin-eosin (H-E), selected sections were stained with Masson trichrome, Gomori reticulin, Congo red and thioflavine S method. Two sections from each case were immunostained for the presence of beta-amyloid (4G8). ubiquitin, alpha-smooth muscle actin and CD31. The different forms of vascular changes were found in all cases. The common changes were: lymphocytic perivascular or transmural infiltrations and hyalinization, thickening or fibrosis of the arterial and arteriolar wall. The perivascular space widening up to status lacunaris was a frequent phenomenon in the basal ganglia and deep white matter. Some of the cortical arterioles formed little multiluminal structures. Immunohistochemical examination revealed features of hypertrophy of the vascular muscular layer and signs of the slight endothelial cells proliferation. In three cases 4G8 immunopositive. Congo red and thioflavine S-negative, diffuse beta-amyloid deposits were present in the gray matter, focally their localization was perivascular. Ubiquitin immunoreactivity presented as numerous dot-like structures or focal bundles of positive widened axons in the white matter, spheroids and scattered positive neurons were also found. The authors suggest that some of morphological changes within the brain and consecutive neuropsychological symptoms in AIDS are of the vascular origin. Presence of amyloid plaques and axonal damage are the elements of the complex degenerative and inflammatory process in the brain caused by chronic inflammatory stimulation in HIV infection.

Recurrent meningiomas--the immunohistochemical analysis of angiogenesis and cellular proliferation. Preliminary study.

Meningiomas exhibit a tendency to the local regrowth after their surgical resection, and some of those recurrent tumors show histological malignancy progression. The present study was performed on 10 cases of recurrent meningiomas chosen out of total 122 meningiomas diagnosed in our Department of Pathomorphology in the period 1993-1998. The tissue material from both operations was examined. One patient was operated three times. In three cases at the second operation there was progression from benign to atypical meningioma. The other tumors did not change their histological grade (four benign, one atypical and two anaplastic). The tumor tissue section were stained immunohistochemically with monoclonal antibodies raised against epithelial membrane antigen (EMA), Ki-67 and von Willebrand factor (vWf). The percentage of EMA-positive cells and Ki-67 immunoreactive cells (proliferation cell index--PCI) were counted. The vascular density (number of blood vessels/mm2) was assessed in the preparations stained with anti-vWf, as the measure of the intensity of angiogenesis. The values of the examined parameters were greatly differentiated within both the initial and the recurrent tumor groups. The values of vascular density ranged 12-96 vessels/mm2, the percentage of EMA-positive cells was 0.75%, PCI was from 0.3 to 9.3%. The values of the examined parameters did not differ significantly between initial and recurrent meningiomas groups. It is however worth to point out that PCI in the most recurrent tumors were higher than in their primary counterparts.

The metastases of lung cancer to the brain--the examination of angiogenesis and p53 expression.

The aim of the present study was to investigate the intensity of angiogenesis and p53 protein expression in metastases of lung cancer to the brain. There were eight cases of squamous cell type and nine adenocarcinomas among 17 examined cases of metastatic carcinomas. The antibodies against von Willebrand factor (vWF)--to highlight the microvessels and against p53 protein--for detection of immunopositive cells were used. The intensity of angiogenesis was represented by the mean number of the blood vessels in three tumor fields with the highest microvascular density ("hot spots"). The measurements were taken in three microscopic fields under 200x magnification (the examined area was 0.785 mm2). The mean number of p53-positive cells in three tumor areas under 200x magnification with the highest number of p53-positive cells was the measure of protein p53 expression. The values of vascular density and p53 expression differed a lot among the examined tumors. The values of vascular density were between 4.2-106 vessels/mm2 (mean value 49.3 vessel/mm2). The number of p53-immunopositive cells was between 0-284 cells/mm2 (mean value 110.6 cells/mm2). There was no significant correlation between examined parameters (correlation coefficient 0.18).

[Difficulties in diagnosis and therapy in a case of brain inflammatory process in patient with Hodgkin's disease]. / Trudnosci diagnostyczne i terapeutyczne w przypadku zapalenia mózgu w przebiegu ziarnicy zlosliwej.

A rare case of cerebral probable viral inflammatory process in a patient with the Hodgkin's disease has been presented. The diagnosis of the neurological disorder was based on the clinical course of the disease, the dynamics of the process observed in CT and MRI examinations. The pathogen was not identified in bacteriological and viral tests. Hodgkin's disease restricted to the spleen was diagnosed in postmortem examination. The presented case demonstrates variability of the clinical picture and difficulties in diagnosing viral encephalitis.

Antiphospholipid syndrome in systemic lupus erythematosus--immunomorphological study of the central nervous system; case report.

We present a case of a 44-year-old female with systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome (APS). The patient died in the 15th year of the disease. The paraffin sections of the brain and spinal cord were examined using routine histological methods and immunohistochemistry with monoclonal antibodies against CD31, FVIIIAg and polyclonal antibodies IgG, fibrinogen and C3. Numerous thrombi-recent, organized and recanalized and focal vasculitis were seen. The immunopositive reaction in thickened vessel walls for CD31 and FVIIIAg indicated the process of the local incorporation of the thrombi. The immunoreactivity for fibrinogen, IgG and C3 suggests the immunological complexes formation in vessel walls, perivascular astrocytes and neurons.

Metastatic carcinoid tumor in the brain.

The case presented describes a metastatic carcinoid in the cerebral hemisphere of a 52-year-old woman. The onset of the disease was in the form of stroke, CT-examination showed hemorrhagic focus and edema. A craniotomy was carried out and the lesion was removed. Histological diagnosis stated that the tumor was a carcinoid accompanied by a massive hemorrhage. Two and a half months later, another CT-examination revealed a second tumor in proximity to the site of operation, which was then treated palliatively by means of Co 60 radiation. The patient died 1.5 months later. General autopsy showed two other neoplastic tumors: a smaller one in the left lung and a bigger one (possible primary) in the stomach. In the report special attention was paid to an unusual cellular polymorphism especially prominent in the tumor formerly irradiated.