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Biomedical subjects

N Weidner

Publications and source records attributed to N Weidner.

At least 19 recordsLinked to original sources

Tumoural vascularity as a prognostic factor in cancer patients: the evidence continues to grow.

Accurate prognostic indicators would help in identifying patients at high risk for recurrence and death. Recent and previous studies indicate that intratumoural microvessel density (iMVD) of invasive breast carcinoma (a measure of tumour angiogenesis) is associated with aggressive tumour growth; iMVD may thus be a valuable prognostic indicator. Moreover, the bulk of accumulating data indicates that microvessel density in the area of most intense neovascularization in invasive breast carcinoma is an independent, significant and accurate prognostic indicator in predicting poorer survival. Such an indicator would be useful in the selection of high-risk patients with breast carcinoma for systemic adjuvant therapy.

Breast Neoplasms

BDNF and TrkB expression in intrastriatal ventral mesencephalic grafts in a rat model of Parkinson's disease.

We investigated the expression of BDNF and its high affinity receptor trkB in fetal dopaminergic grafts in a rat model of Parkinson's disease. Grafts were allowed to differentiate for 7, 14, 28, or 56 days, respectively and were analyzed immunocytochemically thereafter with antibodies directed against tyrosine hydroxylase, BDNF and trkB. At all time points investigated, grafts contained tyrosine hydroxylase immunoreactive neurons. Immature grafts (7 days) displayed no immunoreactivity for BDNF which was restricted to glial cells at the graft-host interface. After longer differentiation periods BDNF-immunoreactivity was detectable in neurons and astrocytes within the grafts. No trkB immunoreactivity was found in immature grafts but a strong signal for trkB emerged in grafted neurons older than 14 days whereas glial cells remained unlabeled at all time points investigated. Expression of BDNF and trkB in grafted neurons and of BDNF in surrounding glial cells suggests an autocrine or paracrine action of BDNF on dopaminergic neurons possibly mediated by activated glia.

Animals

Prognostic significance of Ki-67 immunostaining and symptoms in resected stage I and II non-small cell lung cancer.

The proliferative rate of a tumor has been considered predictive of its clinical course. We evaluated the expression of the proliferative marker Ki-67 and its relationship to survival, disease-free survival and other clinicopathologic variables in both stage I and stage II non-small cell lung cancer (NSCLC). A total of 260 patients with surgically resected stage I (n = 193), and II (n = 67) NSCLC with at least 5 years follow-up were identified. The median survival for patients with low expression of Ki-67 (< or = 25%) was 54 months, while for those with high expression (> 25%), it was 45 months (P = 0.1). The disease-free survival in patients with low expression of Ki-67 was 59 months while it was only 32 months for patients with high Ki-67 (P = 0.1). Out of 136 patients, 84 (62%) had both increased S-phase (> 8%) and high Ki-67 (P = 0.001). A total of 28 of 30 patients who had loss of antigen A had high expression of Ki-67 (93.3%) (P = 0.03). Ki-67 expression was also higher in squamous cell (54/63, 85.7%) compared to nonsquamous cell cancer (70/108, 64%) (P = 0.03). We also analyzed for the presence of symptoms with survival. The presence of symptoms was not found to be statistically significant, for overall survival (P = 0.33) or disease-free survival (P = 0.72). When individual symptoms were analyzed, the presence of cough was statistically significant for both overall and disease-free survival. The median survival was 39 months for patients with cough, and 57 months for patients without cough (P = 0.04). Multivariate analysis showed higher N and T stages, presence of cough and loss of antigen A, predicted for poorer overall survival. Higher N and T stages, loss of antigen A, presence of mucin and cough and increased expression of Ki-67 predicted decreased disease-free survival. Although we did not find a statistically significant difference between low and high Ki-67, there was a trend for a poorer overall and disease-free survival in patients with high Ki-67 expression. Larger studies may be needed to prove a statistically significant effect of Ki-67 on survival. Future studies should assess the potential prognostic significance of the presence of symptoms (particularly cough) in addition to clinical-pathologic variables (such as T and N stage) and biological markers in patients with early stage NSCLC.

Aged

Genetic alterations in lobular breast cancer by comparative genomic hybridization.

Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are distinguished by their histopathological appearance. However, little is known about the differences in genetic changes between lobular cancers and ductal cancers. We used comparative genomic hybridization (CGH) and compared aberrations in 19 ILCs and 46 IDCs. The total number of aberrations was lower in ILC than in IDC. While the average number of DNA copy number losses did not reach significance between them, copy number gains were significantly lower in ILCs. Fifteen of 19 ILCs (79%) showed increased copy number of 1q, and 12 cases (63%) revealed loss of 16q. The presence of these aberrations was independent of nodal status, histologic subtypes (pleomorphic or classic ILC), or BrdUrd-labeling index. ILCs had a higher frequency of 16q loss than did ductal cancers, and a lower frequency of 8q and 20q gains. Our data suggest that the altered growth pattern and clinical presentation which characterize infiltrating lobular cancers are correlated with distinct genetic alterations.

Adult

Collision tumor: a peripheral neuroepithelioma and a transitional-cell carcinoma occurring simultaneously in the renal pelvis.

We report a unique case of a collision tumor of the kidney composed of a peripheral neuroepithelioma (PNE) and a transitional cell carcinoma (TCC) that occurred in a 67-year-old man with a long history of superficial TCC of both the bladder and bilateral upper urinary tracts. The PNE was composed of hyperchromatic, small, round cells, arranged in clusters and poorly cohesive sheets. Immunohistochemical studies revealed the small cells to be strongly positive for O13 (ie, a MIC2 gene product stain [CD99]) and vimentin. Electron microscopic examination found numerous interdigitating cell processes, multiple poorly formed cell-cell junctions, and dense-core granules. The latter were most conspicuous at the tips of the cell precesses. The PNE cells were clearly negative for cytokeratin, and they showed no transitional or intermediate features that would suggest evolution of the PNE from the adjacent TCC. The proximity of these two tumors appears to be serendipitous; thus, it can be considered a true collision tumor of the kidney.

12E7 Antigen

The insulin receptor content is increased in breast cancers initiated by three different oncogenes in transgenic mice.

The Insulin Receptor (IR) is a potential oncogene for mammary epithelial cells since its content is increased in most human breast cancer specimens, and both ligand-dependent malignant transformation and ligand-dependent enhanced growth occurs in cultured breast cells overexpressing the IR. To better understand whether the IR plays a role in mammary carcinogenesis which is independent of other initiation factors, we measured IR content in transgenic mouse models of breast cancer induced by 3 known oncogenes (Wnt-1, Neu, and Ret). Insulin receptor content was measured by a specific radioimmunoassay. In normal mammary gland tissues IR content was 14.6 +/- 1.4 ng/mg of protein (mean +/- SEM, n = 6). In the 3 cancers IR content was elevated (Neu = 36.1 +/- 4.6, n = 8, p < 0.002; Wnt-1 = 38.3 +/- 2.6, n = 13, p < 0.001; and Ret = 53.6 +/- 7.1, n = 7, p < 0.001). These data indicate that IR overexpression, in addition to being a potential oncogene, is increased in mouse tumors initiated by other oncogenes, and therefore may also play a supportive role in the growth of breast cancers.

Animals

Hodgkin's disease of the esophagus.

A 61-year-old man with acquired immunodeficiency syndrome (AIDS) sought care because of the onset of progressive dysphagia. He was found to have a perforated, fungating esophageal mass. The combined histologic and immunologic findings were diagnostic of Hodgkin's disease, nodular sclerosis type, lymphocyte-depleted variant, arising in the esophagus. The Reed-Sternberg cells and mononuclear variants were positive for Epstein-Barr virus (EBV) latent membrane protein (LMP1) and EBV RNA. Occasional small lymphoid cells were also positive for EBV RNA. Polymerase chain reaction studies demonstrated the presence of EBV type A without deletion of the EBV LMP1 gene. Other authors have reported an increased frequency of type B EBV and deletion of the EBV LMP1 gene in cases of human immunodeficiency virus-associated Hodgkin's disease. Hodgkin's disease arising in the esophagus is rare in immunocompetent patients. However, in the presence of AIDS, Hodgkin's disease should be considered in the differential diagnosis of patients with signs or symptoms of esophageal disease.

Acquired Immunodeficiency Syndrome

Diabetes insipidus from sarcoidosis confined to the posterior pituitary.

A young white man with new-onset central diabetes insipidus was discovered to have a posterior pituitary mass on magnetic resonance imaging. No other radiological abnormalities were noted in the anterior pituitary, infundibulum or hypothalamus. No other endocrinopathies were present: laboratory investigations showed normal basal concentrations of anterior pituitary hormones, including prolactin. The patient was suspected to have sarcoidosis affecting the posterior pituitary, because of the discovery of pulmonary sarcoidosis during his diagnostic evaluation. His symptoms of polydipsia and polyuria responded promptly to intranasal administration of 1-desamino-8-D-arginine vasopressin (DDAVP). The patient demonstrated complete regression of the posterior pituitary mass after a course of corticosteroid therapy. However, his diabetes insipidus persisted and he continues to need DDAVP treatment, currently at 12 months of follow-up. The resolution of the neurohypophysial mass was compatible with the diagnosis of pituitary sarcoidosis and this precluded the need for a transsphenoidal biopsy or surgery.

Adrenal Cortex Hormones

Pathologic prognostic factors for patients with breast carcinoma. Which factors are important.

Current technologies can identify subsets of patients who are at greater risk for developing recurrent carcinoma. This article presents conventional and generally accepted pathologic features of breast carcinoma that allow breast carcinoma patients to be placed into low-risk or high-risk categories for recurrence-free or overall survival. Also, the role of flow cytometry, estrogen-progesterone receptor measurement, tumor angiogenesis, and selection oncoprotein expression, such as c-erbB2, are reviewed.

Breast Neoplasms

Relationship of tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer.

The purpose of this investigation was to evaluate the relationship between tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer. We studied 161 patients with invasive transitional cell carcinoma of the bladder who had previously undergone radical cystectomy. Analysis was performed to determine the presence of p53 nuclear accumulation and extent of tumor-associated angiogenesis. p53 status identified a group of patients at high risk for tumor progression (p53-altered tumors), and microvessel density determinations added additional prognostic information by identifying a subset of aggressive tumors within the wild-type p53 subgroup. At 5 years, patients with tumors exhibiting no evidence of p53 alterations and low microvessel counts demonstrated 3% recurrence and 88% survival, compared to 43% recurrence and 59% overall survival for patients with intermediate vessel counts and 61% recurrence and 43% overall survival for patients with the highest vessel counts (P < 0.001 and P = 0.003, respectively). Angiogenesis also provides additional prognostic information to patients with tumors that demonstrate p53 alterations. An association between angiogenesis and p53 status did exist (P = 0. 05); however, 27% of the tumors that showed no evidence of p53 alterations exhibited high microvessel counts, and 26% of tumors with evidence of p53 alterations had low microvessel counts. Tumor-associated angiogenesis adds additional useful prognostic information to that which is obtained from p53 status in patients with invasive transitional cell carcinoma of the bladder. Although an association between p53 status and the degree of angiogenesis was identified, other factors appear to play a role in the regulation of tumor-induced neovasularization.

Biomarkers, Tumor

New prognostic factors in nasopharyngeal carcinoma. Tumor angiogenesis and C-erbB2 expression.

BACKGROUND: This study was conducted to determine the prognostic significance of tumor angiogenesis, c-erbB2, epidermal growth factor receptor, Ki-67, and p53 for patients with nasopharyngeal carcinoma. METHODS: In this retrospective study, the authors retrieved clinical data and made immunohistochemical preparations on archival tissue specimens from 30 patients with nasopharyngeal carcinoma treated with radiation therapy at the University of California at San Francisco between 1956 and 1990. The pretreatment clinical and immunohistochemical data were correlated with cervical lymph node metastasis at diagnosis, and endpoints including development of locoregional failure, distant metastasis, disease free survival, and overall survival. RESULTS: Intense tumor angiogenesis, defined as microvessel counts for 60 or more microvessels per 200 x field correlated with the development of distant metastasis (P = 0.03), shorter overall survival (P = 0.02), and disease free survival (P = 0.05). Strong c-erbB2 expression correlated with a shorter overall survival (P = 0.02) and disease free survival (P = 0.02). Stage IV disease (P = 0.04) and the presence of cervical lymph node metastasis (P = 0.05) correlated with a shorter overall survival. A duration of symptoms of fewer than 6 months correlated with a shorter disease free survival (P = 0.05). No association was observed between any of the biologic prognostic factors and lymph node involvement or locoregional failure. CONCLUSIONS: The results of this study show that the tumor angiogenesis and c-erbB2 expression are significant prognostic indicators for patients with nasopharyngeal carcinoma. The presence of cervical lymph node metastasis, Stage IV disease, and a duration of symptoms fewer than 6 months also indicate a poor prognosis. The authors did not find any prognostic significance for epidermal growth factor receptor, Ki-67, or p53. These results suggest that tumor microvessel counts and c-erbB2 may be useful in identifying patients who may benefit from systemic chemotherapy or other novel treatment strategies.

Adolescent

Post-irradiation malignant mesothelioma.

BACKGROUND: Approximately 30 patients with malignant mesothelioma following radiotherapy have been described. Population-based studies of this occurrence have not been reported. METHODS: Patients with malignant mesothelioma of the pleura were collected. All of the patients had a prior cancer and had received radiotherapy to the region in which the malignant mesothelioma developed. Data from the National Cancer Institute's Surveillance, Epidemiology and End Results Program and the Connecticut Tumor Registry were evaluated for cases of malignant mesothelioma of the pleura occurring in patients with a previous cancer. The literature on post-irradiation malignant mesotheliomas was reviewed. RESULTS: Eight patients (4 men, 4 women) with malignant mesothelioma occurring in sites of radiotherapy for a prior tumor were identified. The mean age at diagnosis of mesothelioma was 45 years (range: 22-78 years), and the average interval between radiotherapy and the mesothelioma was 21 years (range: 11-29 years). Three of the patients had also received chemotherapy. Histologically, the mesotheliomas were epithelial in five cases, biphasic in one, and sarcomatous in one. One hundred forty-two patients were identified in the epidemiologic survey. The majority were men (89%), with a mean age for all patients of 68.5 years (range: 35-86 years) and a median latency between first cancer and mesothelioma of 4.3 years (range: 2 months-29.9 years). CONCLUSIONS: Mesotheliomas rarely develop as second malignant neoplasms. Within a large, population-based survey of patients with cancer, temporal patterns and demographic features of most second primary mesotheliomas were similar to asbestos-related tumors, although the late effects of cancer treatment might have contributed to the occurrence of cancer in some patients.

Adult

Diffuse colonic mantle cell lymphoma in a patient with presumed ulcerative colitis: detection of a precursor monoclonal lymphoid population using polymerase chain reaction and immunohistochemistry.

Primary lymphoma of the colon, a rare and typically late complication of ulcerative colitis, exhibits high-grade morphology and behavior when it occurs. Recently, several reports of colonic lymphoma masquerading as ulcerative colitis have been described. These previous reports described inflammatory mucosal changes typical of ulcerative colitis as being present in superficial biopsies, leading to the initial diagnosis of ulcerative colitis; however, further workup resulted in a diagnosis of primary colonic lymphoma within several months in these cases, and all symptoms and mucosal changes resolved after treatment of the lymphoma. Herein we report a case of mantle cell lymphoma arising in the colon and rectum in a 71-year-old woman with a 4-year history of ulcerative colitis. Immunoglobulin heavy-chain gene rearrangements were detected using the polymerase chain reaction procedure in fixed tissue in the lymphoma as well as in a prior resection specimen that histologically appeared to show only changes of severe ulcerative colitis. This finding suggests that an indolent lymphoid proliferation may have been the underlying disease in this patient and raises questions about the role of colonic lymphoma in causing mucosal injury.

Aged

Solitary fibrous tumor involving the renal capsule.

Solitary fibrous tumors are spindle-cell neoplasms that originally were described in the pleura but that can occur in a large variety of sites. We report a well-circumscribed tumor, apparently involving the renal capsule, clinically thought to be a renal-cell carcinoma or oncocytoma. It was composed of bland spindle-shaped cells with a patchy lymphoplasmacytic infiltrate, suggesting sarcomatoid renal-cell carcinoma, inflammatory myofibroblastic tumor, or solitary fibrous tumor; however, immunohistochemical stains were negative for keratin, alpha-smooth-muscle actin, and desmin but strongly positive for CD34. Ultrastructural examination revealed fibroblast-like cells without myofibroblastic or epithelial differentiation. The combined findings favor a diagnosis of a solitary fibrous tumor involving the renal capsule. To our knowledge, this lesion has not been reported in this location.

Antigens, CD34