Ratiometric confocal Ca2+ measurements with visible wavelength indicators in d-amphetamine-treated central snail neuron

Cyclin E gene alteration in the cell cycle plays an important role in carcinogenesis, while p53 protein affects different phase checkpoint pathways by activating p21WAF1/CIP1 in the normal cell cycle. We immunohistochemically examined the expression of cyclin E and p53 proteins in 121 patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter to determine their significance for tumour behaviour and patient prognosis. Cyclin E and p53 immunostaining of the nucleus was observed in 36 tumours (29.8%) and 35 tumours (28.9%) respectively. A significant percentage, 69.4% (25 out of 36 tumours), of the cyclin E-positive tumours exhibited simultaneous labelling for p53 (P < 0.05). Mirror-section technique was performed in five selected double-positive tumours to identify cancer cells that were nuclei positive for both cyclin E and p53. The prevalence of cases simultaneously exhibiting both cyclin E and p53 immunostaining was higher in the high-grade tumours (P < 0.01) than in the other types of tumours. Patients with TCCs coexpressing cyclin E and p53 had a significantly poorer prognosis than those expressing neither cyclin E nor p53 (P < 0.001). These in vivo findings provide evidence for cyclin E protein overexpression in TCCs intimately associated with p53 alteration and suggest that simultaneous overexpression of both cyclin E and p53 is related to tumour behaviour and poor prognosis.     

P53 overexpression in head and neck carcinoma and radiotherapy results

PURPOSE: P53 gene mutations are the common genetic changes encountered in human cancers, and there is extensive evidence that the P53 status may determine tumor response to therapy. This study was carried out to investigate whether there is any correlation between accumulation (overexpression) of P53 protein and poor prognosis in patients with head and neck carcinomas treated with radical radiotherapy. METHODS AND MATERIALS: Seventy-nine patients with head and neck carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy were studied retrospectively. Paraffin sections from archival material were studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies (D0-7) to human P53 protein. Univariate and multivariate analysis of loco-regional tumor control and patient survival were performed on possible prognostic factors. RESULTS: Forty-two (53%) patients showed positive IHC staining in their tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43% of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The proportion of tumor-stained nuclei was higher in the poorly differentiated than in the well and moderately differentiated tumors (p < 0.05), but there was no correlation with the patient overall or disease-free 5-year actuarial survival. There was no difference in the 5-year actuarial survival and disease-free survival between patients with P53 immunostaining in their tumors and those with no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor stage was the most significant prognostic factor with 5-year actuarial survival of 87% for early and 14% for late stages (p < 0.0001). There was a significant correlation between immunostaining and history of smoking (p = 0.02). CONCLUSION: The data demonstrate that the P53 accumulation as detected by immunohistochemical staining in a group of head and neck carcinomas was not predictive of patient's poor survival or disease-free survival. Multivariate statistical analysis showed that the TNM tumor stage was the only significant prognostic factor. There was a significant association between P53 accumulation and smoking.     

Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance

To evaluate the prognostic significance of immunohistochemically detected p53 and Bcl-2 proteins in colorectal cancer, tissue sections from 238 paraffin-embedded colorectal carcinomas were immunostained for p53 (MAb DO-7 and CM-1 antiserum) and Bcl-2 (MAb Bcl-2:124). Staining patterns were assessed semiquantitatively and correlated with each other and with sex, age, tumour site, Dukes' classification, tumour differentiation, mucinous characteristics, lymphocyte and eosinophilic granulocyte infiltration, and patient survival. In our series, 35% of carcinomas showed no nuclear staining and 34% (DO-7) to 40% (CM-1) showed staining in over 30% of tumour cell nuclei. A majority of carcinomas that had been immunostained with CM-1 showed cytoplasmic staining, but this was not observed with DO-7. With respect to Bcl-2, 51% of tumours were completely negative, 32% displayed weak and 15% moderate staining; only 3% showed strong positive staining. No evidence was found for reciprocity between Bcl-2 expression and nuclear p53 accumulation. From 13 cases containing tumour-associated adenoma, four were Bcl-2 negative in premalignant and malignant cells, in another four cases these cells showed similar staining intensities and in the remaining cases only the malignant colorectal cells were Bcl-2 negative. Therefore, our data indicate that Bcl-2 is dispensable in the progression towards carcinoma. Except for an association between nuclear p53 accumulation and mucinous tumours (P = 0.01), no significant correlation was found between the clinicopathological parameters mentioned above and immunostaining pattern of (nuclear or cytoplasmic) p53 or Bcl-2.     

Acute hemorrhagic pulmonary infarction and necrotizing pneumonia in horses: 21 cases (1967-1993)

Specimens of formalin-fixed, paraffin-embedded non-small-cell lung carcinomas (NSCLCs; n = 187) were analysed immunohistochemically for expression of cyclin A. The analysis was intended to determine whether cyclin A has additional prognostic value for predicting patients' survival and drug response. Of the 187 NSCLCs, 141 cases (75%) showed expression of cyclin A. Patients with cyclin A-positive carcinomas had significantly shorter median survival times than patients with cyclin A-negative carcinomas (79 vs 129 weeks, P = 0.045). Similar results were obtained with more homogeneous groups of patients: patients with only T3 tumours, patients with epidermoid carcinomas and patients with lymph node involvement. The clinical parameters (age, stage, histology, extent of tumour size, lymph node involvement) had no influence on expression of cyclin A. A direct correlation between cyclin A and the proportion of S-phase cells (P = 0.08) and an inverse relationship between cyclin A and the proportion of G0/G1-phase cells (P = 0.04) were found. Furthermore, a significant correlation between the expression of cyclin A and the response of NSCLC to doxorubicin in vitro was detected (P = 0.026).     

Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine lung tumors

Neural cell adhesion molecules (NCAM) represent specific markers of neuroendocrine (NE) differentiation in lung cancer. Because the polysialic acid form (NCAM-PSA) has reduced adhesion properties, we hypothesized that NCAM-PSA expression could favor metastatic spread. Immunostaining of NCAM and NCAM-PSA were therefore compared in 120 NE lung tumors, including 17 typical carcinoids, 3 atypical carcinoids, 30 large cell NE carcinomas and 70 small cell lung carcinomas, as compared with 25 adenocarcinomas and 25 squamous cell carcinomas. Neural cell adhesion molecules were negative in adenocarcinomas and squamous cell carcinomas but were constantly expressed in all NE tumors from typical carcinoids to small cell lung carcinomas. NCAM-PSA expression was significantly more frequent in high-grade tumors, with 24 of 30 positive cases in large cell NE carcinomas and 65 of 70 positive cases in small cell lung carcinoma, than in carcinoids with 10 of 17 and 2 of 3 positive cases in typical carcinoids and atypical carcinoids, respectively. The neural cell adhesion molecule-polysialic acid form scores of staining were significantly higher in high-grade as compared with low-grade tumors (p = 0.002), and were correlated with nodal spread (p = 0.04) and metastasis (p = 0.016) across histologic classes but not in individual tumor type. We conclude that NCAM-PSA connotes poor differentiation and aggressive clinical behavior in the spectrum of NE lung tumors, but cannot be regarded as a prognostic factor in individual tumor classes.     

Abnormal expression of CCND1 and RB1 in resection margin epithelia of lung cancer patients

Tumours develop through the accumulation of genetic alterations associated with a progressive increase of the malignant phenotype. In lung cancer, chronic exposure of bronchial epithelium to carcinogens in cigarette smoke may lead to multiple dysplastic and hyperplastic lesions scattered throughout the tracheobronchial tree. Little is known about the genetic alterations in such lesions. This study was carried out to examine cyclin D1 (CCND1) and retinoblastoma (RB1) gene expression in the bronchial epithelium of patients with lung cancer. Lung tumours and their corresponding tumour-free resection margins from 33 patients who underwent resection of non-small-cell lung cancer (NSCLC) were examined by immunostaining with monoclonal antibodies against cyclin D1 (DCS-6; Novocastra) and pRb (NCL Rb-1; Novocastra). Examination of the resection margins revealed four carcinomas in situ, 19 hyperplasias and ten sections showing apparently normal bronchial epithelium. A control group of patients, without lung tumours and who had never smoked, revealed no or weak cyclin D1 and positive pRb staining within bronchial epithelia. Increased cyclin D1 and diminished pRb expression were found in 76% (n = 25) and 27% (n = 9) of the resection margins respectively, and in 12% (n = 4) both cyclin D1 and pRb expression were altered. In the corresponding tumours, 48% (n = 16) were normal, while altered expression was found for cyclin D1 in 33% (n = 11), pRb in 27% (n = 9) and both in 9% (n = 3) of cases. It appears that altered expression of cyclin D1 and pRb is an early event in NSCLC development in almost half of cases analysed. Further investigations are needed to determine the significance of immunostaining of bronchial specimens in individuals at risk of lung cancer, with the possibility that the observations are of importance in the early diagnosis of NSCLC.     

Expression of proliferating cell nuclear antigen (PCNA) in gastric carcinoma: no evidence for prognostic value

It has been proposed that immunostaining with PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA), is of prognostic value in gastric carcinoma. Gastric carcinomas from a series of 90 patients in whom survival data were known have been studied. There was no relation between the degree of PC10 immunostaining assessed semiquantitatively and survival.     

A phase II trial of weekly infusional 5-fluorouracil in combination with low-dose leucovorin in patients with advanced colorectal cancer

We examined 59 breast cancers for p53 and bcl-2 protein expression by immunohistochemistry. The results were correlated with Ki-67 immunostaining. p53-negativity was noted in 40 cases and the remaining 19 tumours were p53-positive. Thirty-six tumours showed strong expression of bcl-2 and in 23 no staining for this protein was observed. We found statistically significant reverse correlation between expression of p53 and bcl-2 in majority of carcinomas: 31 cases were bcl-2 positive and p53-negative, and 14 tumours were bcl-2-negative and p53-positive. Six carcinomas showed no nuclear staining for Ki-67 and in the remaining 53 the percent of cancer cells positive for Ki-67 ranged from 1 to 60 (mean: 14.6). In these 53 cases we found that bcl-2-positive tumours were characterized by lower proliferation than bcl-2-negative tumours, the mean value of Ki-67 immunostaining being 10.7% and 23.0%, respectively. p53-negative tumours showed lower proliferation than p53-positive tumours: mean Ki-67 index was 10.2% and 23.9%, respectively. We conclude that immunohistochemically detected p53 and bcl-2 proteins show a significant inverse relationship in majority of breast carcinomas and their expression correlates with tumour proliferation (Ki-67 immunostaining).     

NCAM140 interacts with the focal adhesion kinase p125(fak) and the SRC-related tyrosine kinase p59(fyn)

Axonal growth cones respond to adhesion molecules and extracellular matrix components by rapid morphological changes and growth rate modification. Neurite outgrowth mediated by the neural cell adhesion molecule (NCAM) requires the src family tyrosine kinase p59(fyn) in nerve growth cones, but the molecular basis for this interaction has not been defined. The NCAM140 isoform, which is found in migrating growth cones, selectively co-immunoprecipitated with p59(fyn) from nonionic detergent (Brij 96) extracts of early postnatal mouse cerebellum and transfected rat B35 neuroblastoma and COS-7 cells. p59(fyn) did not associate significantly with the NCAM180 isoform, which is found at sites of stable neural cell contacts, or with the glycophosphatidylinositol-linked NCAM120 isoform. pp60(c-)src, a tyrosine kinase that promotes neurite growth on the neuronal cell adhesion molecule L1, did not interact with any NCAM isoform. Whereas p59(fyn) was constitutively associated with NCAM140, the focal adhesion kinase p125(fak), a nonreceptor tyrosine kinase known to mediate integrin-dependent signaling, became recruited to the NCAM140-p59(fyn) complex when cells were reacted with antibodies against the extracellular region of NCAM. Treatment of cells with a soluble NCAM fusion protein or with NCAM antibodies caused a rapid and transient increase in tyrosine phosphorylation of p125(fak) and p59(fyn). These results suggest that NCAM140 binding interactions at the cell surface induce the assembly of a molecular complex of NCAM140, p125(fak), and p59(fyn) and activate the catalytic function of these tyrosine kinases, initiating a signaling cascade that may modulate growth cone migration.     

Neural networks as a prognostic tool for patients with non-small cell carcinoma of the lung

Patients with non-small cell carcinoma of the lung (NSCLC) have a poor prognosis (64 and 41% survival rates in Stages I and II). It is currently not possible to predict which patients with Stage I or II NSCLC will survive the disease. Sixty-seven patients with NSCLC, including 49 patients with Stage I NSCLC and 18 with Stage II disease (11 with squamous cell carcinomas, 35 with adenocarcinomas, and 21 with large cell carcinomas) were treated with lobectomy and followed for a minimum of 5 years. The tumors were studied with DNA flow cytometry and quantitative immunocytochemical studies for proliferation cell nuclear antigen, p53 protein, and MIB-1. The data were analyzed with backpropagation neural networks, univariate analysis of variance, the Kaplan-Meier survival method, and Cox proportional hazards model. The dependent variables were "free of disease" and "recurrence or dead from disease." Twenty neural network models were trained, using all cases but one, after 1883 to 2000 training cycles. At 5 years, 30 patients were free of disease and 37 were dead or had recurrence. Proliferating cell nuclear antigen was the only statistically significant prognostic factor by univariate analysis of variance and Cox proportional hazards analysis. The S phase was statistically significant by univariate analysis of variance (P <.05). All of the 20 models classified the test cases correctly. Study with backpropagation neural networks using multiple prognostic features from patients with NSCLC suggests that this technology might be useful for prediction of survival. This preliminary study must be validated with data from a larger group of patients with NSCLC before its clinical adequacy is established.     

The PRAD-1/cyclin D1 oncogene product accumulates aberrantly in a subset of colorectal carcinomas

The PRAD-1/cyclin D1 proto-oncogene is localized on chromosome 11q13 and it is overexpressed in several tumour types as a consequence of gene amplification or chromosomal rearrangements. In this study, the abundance and patterns of cyclin D1 protein expression in normal/non-involved colon (n = 44), primary (n = 48) and metastatic (n = 9) colorectal carcinomas, and in a series of 4 colon cancer cell lines were investigated by immunochemical methods using the DCS-6 monoclonal antibody specific for cyclin D1. While examination of all normal colorectal tissue samples and 56% of the primary tumours revealed only weak to undetectable immunostaining signals, 23% of the primary carcinomas showed moderate and 21% showed strong aberrant accumulation of this cell-cycle regulatory oncoprotein. The immunohistochemical patterns in the secondary lesions were concordant with the matched primary tumours in all cases. The staining was nuclear both in the clinical specimens and in the colon cancer cell lines, in which the antibody-mediated knock-out experiments demonstrated a positive regulatory role of the cyclin D1 protein whose function was required for progression through the G1 phase of the cell cycle. These results indicate that the PRAD-1/cyclin D1 protooncogene may be deregulated in a significant subset of colorectal tumours, and warrant further analyses of such aberrations of the cyclin D1/retinoblastoma protein pathway to elucidate its potential involvement in the multistep pathogenesis of human colorectal cancer.     

Thrombospondin-1 and its CSVTCG-specific receptor in wound healing and cancer

Accumulation of mutant p53 protein occurs frequently in human malignancies, including 40-60% of non-small cell lung carcinomas. The implications of such p53 over-expression, usually assessed by immunohistochemical techniques, for the prognosis of lung cancer patients remain undetermined. In this study, we used a time-resolved immunofluorometric assay to measure p53 protein concentrations in extracts prepared from 86 primary non-small cell lung tumours and examined the associations between p53 protein levels (corrected for total protein) and other clinico-pathologic variables, including post-surgical disease-free and overall survival. Contingency tables analysed by chi2 tests revealed no significant relationships between p53 status, defined by a median cut-off point, and patient gender, age, disease stage, histologic grade and type, lymph node extension, smoking history and administration of adjuvant chemotherapy or radiation. However, multivariate Cox proportional hazard regression analysis demonstrated a dose-response relationship between p53 concentration, expressed as a 4-level, quartile-divided variable, and increased risk of relapse (p = 0.010) and death (p = 0.016). Patients whose tumours contained p53 concentrations exceeding the median value had over 3-fold higher risk of relapse (p = 0.002) and death (p = 0.007) than those whose tumours had lower p53 concentrations. We also provide evidence suggesting that the impact of p53 on survival is greater in patients with squamous cell carcinoma than in those with adenocarcinoma. Although the latter finding needs confirmation, our results suggest that application of an immunoassay of p53 protein on non-small cell lung tumour extracts may identify patients at increased risk of unfavourable outcome.     

Biological indicators of survival in patients treated by surgery for squamous cell carcinoma of the oral cavity and oropharynx

Squamous cell carcinomas of the head and neck are a heterogeneous group of tumours with regard to anatomical site, natural history and response to various treatments. Assessment of the role of biomarkers as indicators of prognosis or response to treatment is thus complex. In the last decade, different biomarkers have been investigated in the search for objective and reproducible indicators of prognosis. In 69 squamous cell carcinomas of the oral cavity or oropharynx from patients treated with radical surgery alone, we determined cell kinetics, evaluated as in vitro 3H-thymidine labelling index (TLI), p53, bcl-2 and glutathione S-transferase pi (GST pi) expression, by using immunohistochemical methods. The biological variables were unrelated to one another or to established clinical and pathological prognostic factors. Univariate analysis showed that a low proliferative activity was associated to a significantly higher risk of death than that observed in patients with a high TLI, whereas p53, bcl-2 and GST pi expression did not provide prognostic information. Multivariate analysis showed that cell proliferation, gender and nodal status retained their clinical relevance. In the subset of node-negative patients, TLI and p53 expression were indicators of survival. Moreover, the combined analysis of TLI and p53 expression identified a subgroup of node-negative patients with slowly proliferating and highly p53-expressing tumours who died within 1 year of radical surgery. These results indicate that in patients with operable oral cavity and oropharyngeal cancer, biomarkers can provide important information on clinical outcome.     

Evaluation of serum neural cell adhesion molecule as a new tumor marker in small cell lung cancer

BACKGROUND: Small cell lung cancer (SCLC) is distinguished from other histologic types of lung cancer by possessing a variety of neuroendocrine properties. Neuron-specific enolase (NSE) is the most frequently elevated tumor marker for patients with SCLC at diagnosis. To assess the value of neural cell adhesion molecules (NCAM), another possible tumor marker for small cell lung cancer, NCAM was evaluated in the sera of patients with histologically confirmed SCLC in two prospective multicenter trials. METHODS: The study includes 221 patients with SCLC, normal human blood donors (n = 34), patients with benign lung disease (n = 53), and patients with non-small cell lung cancer (n = 28). NCAM was determined by means of an enzyme immunoassay, NSE by a radioimmunoassay. RESULTS: The data show the following: (1) 51% (113 of 221) of all patients with SCLC had NCAM levels higher than 20 U/ml, 34% (75 of 221) had NSE levels higher than 25 ng/ml; (2) levels of both markers significantly differ between limited and extensive disease patients; (3) patients with pathologic NCAM and NSE levels have significantly shorter survival times; (4) a positive correlation between pretreatment NSE and NCAM levels was found (n = 221, r = 0.60); and (5) a correlation between serum marker levels and clinical status was found in follow-up studies of 19 patients. CONCLUSIONS: From these data, it is concluded that NCAM is, along with NSE, a potential tumor marker for SCLC.     

Altered retinoblastoma and p53 protein status in non-small cell carcinoma of the lung: potential synergistic effects on prognosis

Routinely processed pathological specimens from 119 patients with stage I and II adenocarcinomas or squamous cell carcinomas were examined by immunohistochemical analysis for altered retinoblastoma (RB) and/or p53 protein expression. Absent RB nuclear staining (RB-) indicating loss of RB function occurred in 19 (16%) of the cases studied, whereas expression of a putative mutant p53 nuclear protein (p53(+)) was found in 54 (45%) of the tumors. The median survival was 39 versus 12 months for patients with RB+ and RB- tumors, respectively (P = 0.05 by log rank analysis). Similarly, the median survival was 41 months for patients whose tumors had no expression of mutant p53 (p53(-)) compared with 24 months for individuals with p53 (+) tumors (P = 0.01). These differences in survival, however, were not statistically significant by multivariate analysis. Nevertheless, individuals with RB-/p53(+) tumors had a significantly shorter median survival (12 months) than those with RB+/p53(-) tumors (41 months), as determined by both log rank and multivariate analyses (P = 0.005 and 0.03, respectively). In addition, 66 large cell carcinomas from all stages were examined. Again, a more significant difference in survival (48 versus 8 months) was found between patients with RB+/p53(-) versus RB-/p53(+) tumors (P = 0. 006). These results suggest that RB and p53 status might be used synergistically as prognostic factors in a subset of non-small cell lung carcinomas.     

Clinical significance of cyclin D1 expression in patients with node-positive breast carcinoma treated with adjuvant therapy

BACKGROUND: Experimental and clinical studies suggest that cyclin D1 is involved in transformation and tumour progression. However, there is little and contradictory data on the clinical significance of cyclin D1 in human invasive breast carcinoma. PATIENTS AND METHODS: We investigated whether the determination of cyclin D1 has prognostic value in a series of 180 patients with node-positive breast carcinoma and treated with adjuvant therapy with a median follow-up exceeding 6 years. We assessed cyclin D1 expression using the CDS-6 monoclonal antibody and a highly sensitive immunohistochemical technique. RESULTS: We found that most of the evaluable tumours (117 of 167; 70.1%) presented nuclear cyclin D1 staining and that its expression was significantly associated with both the hormone receptors (P = 0.009 and P = 0.005 for ER and PgR, respectively). Furthermore, 29 (17%) of 167 tumours had a weak (15 cases) or strong (9 cases) cytoplasmic cyclin D1 staining. In a subgroup of cases we also studied the amplification of the cyclin D1 gene and a moderate agreement between cyclin D1 nuclear overexpression assessed immunohistochemically and the gene amplification was found. In univariate analysis, cyclin D1 nuclear positivity was significantly associated with improved 6-year relapse-free survival (RFS) (P = 0.004), but not with overall survival (OS) (P = 0.12). The results of the Cox multivariate analysis (final model) indicate that cyclin D1 expression (P = 0.0049) as well as the number of involved nodes (P < 0.001) and tumour size (P = 0.036) are significant prognostic indicators for RFS. Only the number of involved nodes retained significance (P < 0.001) for OS in our series. The joint assessment of the variables considered in the final model of the multivariate analyses had a moderate prognostic capability as determined using the Harrell c statistic (c = 0.66 and 0.64 for RFS and OS, respectively). CONCLUSIONS: The patients with node-positive breast cancer who have a higher likelihood of gaining benefit from adjuvant therapy are those with tumours with cyclin D1 nuclear expression, small size and less than 3 metastatic nodes. Further studies are needed to verify the prognostic value of cyclin D1 in relation to different adjuvant treatments and to deepen the biological pathways that regulate its activation/ suppression in human breast carcinoma.     

Expression of p53 protein has no independent prognostic value in breast cancer

A series of 392 female breast carcinomas was analysed immunohistochemically for expression of p53 protein with special emphasis on the role of p53 as an independent prognostic factor. Altogether, 54.8 per cent of the carcinomas expressed p53 protein, with the mean [standard error (SE)] fraction of positive nuclei being 17.1 per cent (1.2 per cent). Expression of p53 protein was independent of tumour metastasis at diagnosis, axillary lymph node status, tumour diameter, histological type, tubule formation, proportion of intraductal growth, margin formation, necrosis, DNA ploidy, and S-phase fraction. A high fraction of p53-positive nuclei was significantly related to patient age under 70 years, high grade, severe nuclear pleomorphism, dense infiltration of tumour by lymphocytes, high mitotic index, and high apoptotic index (for all, P < 0.05). Impaired survival probability in the entire cohort (P = 0.05) and in the axillary lymph node-positive (ANP) tumours (P = 0.015) was associated with a fraction of p53-positive nuclei less than 25 per cent, while in the axillary lymph node-negative (ANN) tumours, expression of p53 had no prognostic value. In multivariate analysis, independent prognostic predictors included axillary lymph node status, tumour diameter, and mitotic index. In the ANN tumours, tumour diameter, fraction of p53-positive nuclei, and tumour grade were independent prognostic factors, whereas in the ANP tumours, diameter and mitotic index were the two independent prognostic factors. The results suggest that abnormal expression of p53 protein is only a weak independent prognostic factor in female breast cancer.     

Expression of neural cell adhesion molecules and neurofilament protein isoforms in skeletal muscle tumors

In a series of rhabdomyosarcomas, the expression of neural cell adhesion molecules (NCAM) and neurofilament isoforms was probed in frozen sections. It was found that NCAM was widely expressed in rhabdomyosarcomas without relation to subtype or differentiation level. Neurofilament isoforms were found throughout all subtypes but were largely restricted to those neurofilament isoforms that are expressed early in neurogenesis, that is, poorly phosphorylated low- and medium-weight isoforms. It was concluded that the expression of these "neural" markers is widespread and does not signify a neural tumor.     

Acute and delayed cerebral infarction after wasp sting anaphylaxis

Mutations and overexpression of p53 gene in prostate carcinoma have been found but their significance in the development and progression of cancer is so far unknown. We investigated the prevalence of abnormalities of p53 protein in a heterogeneous group of prostate carcinoma to verify whether acinar and non acinar carcinomas have a different expression of p53 protein. Paraffin sections of 45 prostate carcinomas (39 acinar, 3 ductal papillary, 1 transitional cell, 1 mucinous and 1 pure small cell) were examined for the expression of p53 protein using a panel of antibodies (monoclonal antibodies Pab 1801, D07 and polyclonal antibody CM1). No p53 expression was observed in any acinar carcinomas independent of grade and stage. For non acinar carcinomas only small cell and transitional cell carcinomas exhibited detectable amounts of p53 protein in tumour cell nuclei. The prevalence of p53 overexpression in prostate carcinoma is relatively low compared with that found in many other tumours. In the present study, the overexpression of p53 in a small cell carcinoma and in a transitional cell carcinoma suggest that the loss of suppressing role of p53 gene may be an important mechanism in the genesis and in the development of these uncommon tumours.