Higher interleukin-6 is associated with greater momentary social connection in close relationships in daily life.

Recent evidence has documented associations between higher levels of inflammation and social approach behaviors toward close others in laboratory-based tasks. Yet it is unknown if this translates to interactions with close others in daily life. Given that momentary experiences of social connection have both relational and health consequences, this is a critical gap in our knowledge. To address the association between inflammation and momentary social connection experiences in close relationships, 55 participants provided blood samples on two consecutive days, which were assayed for circulating levels of the inflammatory marker interleukin-6 (IL-6). After providing the first blood sample, participants received the annual influenza vaccine as a mild inflammatory challenge. Participants also reported on cognitive, affective, and behavioral indicators of social connection with a specific close other multiple times across the two study days. Results indicated that levels of IL-6 were positively associated with temporally-proximal indicators of momentary social connection with a close other. Specifically, higher levels of IL-6 were associated with greater feelings of comfort from the close other, greater desire to be near them, and higher reported relationship quality. Greater IL-6 reactivity to the vaccine was only associated with increased reported relationship quality. These data add to the existing literature suggesting that higher levels of IL-6 may motivate social approach toward a close other, extending evidence to now include momentary social connection experiences in daily life.

Inflammatory reactivity to the influenza vaccine is associated with changes in automatic social behavior.

Recent evidence suggests differential patterns of social behavior following an inflammatory challenge, such that increases in inflammation may not uniformly lead to social withdrawal. Indeed, increases in inflammation have been associated with enhanced self-reported motivation to approach a specific close other, and greater neural sensitivity to positive social cues. However, no known studies have examined the association between inflammation in response to an inflammatory challenge and social behavior in humans, nor has past research examined specifically how approach and withdrawal behavior may differ based on whether the target is a close other or stranger. To address this, 31 participants (ages 18-24) received the influenza vaccine to elicit a low-grade inflammatory response. The morning before and approximately 24 h after the vaccine, participants provided a blood sample and completed a computer task assessing automatic (implicit) approach and withdrawal behavior toward a social support figure and strangers. Greater increases in the inflammatory cytokine interleukin-6 (IL-6) in response to the vaccine were associated with an increase in accuracy in avoiding strangers and a decrease in accuracy in approaching them. Increases in IL-6 were also associated with a decrease in reaction time to approach a support figure, but only when controlling for baseline IL-6 levels. There were no associations between change in IL-6 and changes in self-reported motivation to engage in social behavior with either close others, or strangers. Together, these findings reveal that increases in inflammation following the influenza vaccine are associated with automatic social behavior, especially behavior suggesting avoidance of unfamiliar social targets and ease in approaching a support figure. These data add to the growing literature suggesting that the association between inflammation and social behavior includes both social withdrawal and social approach, depending on the specific target.

Percutane Image-Guided Cryoablation of Painful Osseous Metastases: A Retrospective Single-Center Review.

PURPOSE: Painful osseous metastases are a common problem in patients with malignancy, and they can be associated with significant morbidity owing to immobility, pain, pathologic fracture, or neurovascular compromise or all of these. We retrospectively evaluated pain levels and tumor enhancement in patients who underwent palliative percutaneous cryoablation for painful bone metastasis. METHODS: In this institutional review board-approved, health insurance portability and accountability act-compliant study, we retrospectively searched our department׳s picture archiving system for patients who underwent computed tomography (CT)-guided percutaneous cryoablation for treatment of painful metastatic osseous disease over a 6-year period (1/1/2005-12/31/2011). The preprocedure and postprocedure images and imaging reports, primary tumor type, CT-guided cryoablation procedure details, treated tumor response, immediate and 3-month postprocedure complications, reported pain response to cryoablation, postprocedural tumor imaging characteristics, and imaging response of noncryoablated systemically treated metastatic lesions were reviewed in patients with metastatic osseous disease who underwent cryoablation. RESULTS: All 16 patients reported improvement in pain within 1 week after the procedure and at 3-month clinical follow-up. A total of 6.2% had tumor growth and 93.8% had tumor arrest or shrinkage on follow-up CT, although all study patients had progression of noncryoablated metastases at other sites despite systemic therapy. A total of 62.5% of patients with posttreatment contrasted CT demonstrated marginal enhancement at the ablation site, although only single patient had interval growth. CONCLUSION: Most of our patients had tumor arrest or shrinkage on follow-up imaging, despite progression of noncryoablated metastases treated with preprocedure and postprocedure systemic therapy. Radiation therapy, chemotherapy, and analgesics have a moderate failure rate and require repeat treatments where quality of life is the foremost objective. CT-guided cryoablation is a safe palliative treatment to reduce pain in patients with painful osseous metastatic disease, achieve effective local tumor control, and in some cases, provide a curative option for a target lesion.

Pelvic Floor Symptoms and Spinal Curvature in Women.

OBJECTIVES: To characterize the association between thoracic (T) and lumbar (L) spinal curvature and pelvic floor (PF) symptoms (pelvic organ prolapse, urinary incontinence [UI], fecal incontinence [FI]). METHODS: Of women undergoing a bone mineral density scan from January 2007 to October 2010, patients who completed PF symptom questionnaires and had T and/or L spine radiographs or computed tomography examinations within 3 years of questionnaire completion were included in this study. The spine angles were measured using the Cobb angle method. The T and L curvatures were categorized as hypokyphosis (<20°), normal T kyphosis (20-40°), hyperkyphosis (>40°), hypolordosis (<40°), normal L lordosis (40-70°), and hyperlordosis (>70°). The presence and type of UI were identified with the 3 Incontinence Questionnaire and FI with the Modified Manchester Questionnaire. Pelvic organ prolapse was defined as a positive response to the presence of a bulge question from the PF Distress Inventory-20. RESULTS: Of 1665 eligible women, 824 and 302 (mean age 64 ± 10 for both) had T and L spine images, respectively. No differences in PF symptoms were observed in the T or L spine groups categorized by hypo-, normal, and hyperkyphosis/lordosis except for urgency UI being more prevalent in the hypolordosis group (P = 0.01). However, upon further characterization using logistic regression, no association was noted between PF symptoms and T or L spine angles; no differences in the mean angles were found between women with versus without PF symptoms (P ≥ 0.05). CONCLUSIONS: The current study shows that the T and L spinal curvatures are not associated with the presence of PF symptoms.

Effect of display magnification on perceived growth of liver lesions on computed tomography.

Our goal was to investigate the effect of displayed image magnification on perception of the size of hepatic lesions on abdominal computed tomography (CT) scans. Institutional review board approval and informed observer consent were obtained. Three experienced radiologists reviewed 90 CT image pairs in one session. Each image pair demonstrated a solitary, well-defined hypodense hepatic lesion measuring greater than 1 cm obtained at two points in time. The image pairs were presented three times in random order, once with the left image magnified, once with the right image magnified, and once with neither image magnified. The radiologists were asked to determine on which image the lesion was smaller or if there was no difference. The responses were analyzed statistically. The proportion of correct responses increased significantly as the difference in lesion size increased (p < 0.001). The percent of correct responses was higher when neither CT image was magnified. Magnification of one image decreased the accuracy of the readers' performance, especially at smaller differences, both of which were statistically significant (p < 0.001). Thus, accuracy of detecting lesion size differences was degraded when the images were presented at differing magnification. This should be kept in mind when evaluating serial CT scans for growth or regression of tumors and other lesions.

Use of neuroendocrine markers, p53, and HER2 to predict response to chemotherapy in patients with stage III non-small cell lung cancer: a Cancer and Leukemia Group B study.

Several studies have suggested that non-small cell lung cancer (NSCLC) patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of p53 and HER2 may confer relative chemotherapy resistance and shortened survival. The Cancer and Leukemia Group B performed a series of studies involving sequential chemotherapy followed by radiation for patients with unresectable stage III NSCLC. The objectives of this study were to analyze pathological specimens using immunohistochemistry for NE markers, p53 and HER2 to determine if there was a correlation between marker expression and response or survival. Of 160 eligible patients, 28 (18%) were not evaluable because of inadequate material. The percentage of specimens positive for markers was as follows: neuron-specific enolase 38%, Leu-7 2%, chromogranin A 0%, synaptophysin 5%, > or =2+NE markers 3%, p53 61%, and HER2 65%. There was no statistically significant correlation between any individual marker and response to induction chemotherapy or response to combined chemotherapy/radiation except for synaptophysin. Six of 6 (100%) synaptophysin positive tumors responded by the completion of all therapy compared with 69/125 (55%) synaptophysin negative tumors (P=0.04). None of the individual markers had a significant effect on survival in univariate analysis. Neuron-specific enolase was marginally significant in multivariate analysis (P=0.08). In conclusion, this study did not demonstrate that expression of NE markers, p53 and HER2 were predictive of response to chemotherapy, combined chemotherapy/radiation or for survival in this group of patients with stage III NSCLC. Future studies must employ either different markers or be performed on more adequate surgical specimens.

Dealing with diversity: recruiting churches and women for a randomized trial of mammography promotion.

There is little documentation about the recruitment process for church-based health education programs. In this study, the authors recruit African American, Latino, and white churches and women members (age 50 to 80) for a randomized church-based trial of mammography promotion in Los Angeles County. Efforts to enhance recruitment began 10 months before churches were invited to participate and included a variety of community-based strategies. Subsequently, 45 churches were recruited over a 5-month period through group pastor breakfast meetings and church-specific follow-up. In close collaboration with the 45 churches, the authors administered church-based surveys over 6 months and identified 1,967 age-eligible women who agreed to be contacted by the program team. It was found that an extended resource intensive period of relationship-building and community-based activities were necessary to conduct church-based programs effectively, particularly among older and ethnically diverse urban populations.

Maintenance of increased Bcl-2 expression in uterine leiomyomas after GnRH agonist therapy.

OBJECTIVE: To compare the immunohistochemical expression of Bcl-2 in uterine leiomyomas in patients undergoing myomectomy or hysterectomy with and without preoperative treatment with the gonadotropin-releasing hormone receptor agonist (GnRH-a) leuprolide acetate (LA). STUDY DESIGN: Retrospective case-control study. Seventeen patients with symptomatic uterine leiomyomata were included. Of the 17 patients, 7 were treated with LA (3.75 mg) in three monthly doses prior to myomectomy or hysterectomy. Ten patients who did not receive LA and underwent hysterectomy for leiomyomas served as controls. Formalin-fixed, paraffin-embedded archival tissue from 17 leiomyomas were immunostained with a monoclonal antibody against Bcl-2 protein. Positivity was scored semiquantitatively on a three-tier scale. RESULTS: Immunostaining for Bcl-2 protein was intense (2-3+) in 7 LA-treated and 10 untreated leiomyomas but was scarce (0-1+) in normal myometrial smooth muscle. CONCLUSION: Abundant expression of Bcl-2 protein may be responsible for the growth of leiomyomas by preventing apoptotic cell death. Its increased expression is maintained in GnRH-a-treated leiomyomas.

Prognostic markers in resected stage I and II non small-cell lung cancer: an analysis of 260 patients with 5 year follow-up.

We performed a retrospective analysis of potential prognostic markers in 260 patients with surgically resected stage I and II non small-cell lung cancer (NSCLC) with a minimum 5-year follow-up. Cox proportional hazard models and Wilcoxon tests were employed to analyze the effect of patient characteristics on survival and disease-free survival (DFS). In the univariate analysis, the following were significant predictors of shorter overall survival: N-stage (N1 vs N0) (p<0.001); T-stage (T2 vs T1) (p<0.001); antigen A (loss vs presence) (p<0.01); cough (present vs absent) (p=0.01); bcl-2 expression (positive vs negative) (p=0.03); age (>63.5 vs <63.5) (p=0.03); mucin (positive vs negative) (p<0.03). The following were significant predictors of shorter DFS: N-stage (p<0.001); T-stage (p=0.001); loss of antigen A (p=0.01); mucin expression (p<0.01); cough (p=0.02); Ki-67 expression (p=0.02) and negative bcl-2 expression (p=0.03). Analysis of survival difference for histologic subtype, degree of differentiation, aneuploidy, %S-phase, codon 12 K-ras mutation, and immunohistochemistry staining for Lewisy, p53, Rb, microvessel count, HER2, E-cadherin and neuroendocrine markers did not reach statistical significance. In multivariate analysis, the following predicted for shorter overall survival: N-stage (p<0.01), antigen A (p=0.01), age (p<0.01), and bcl-2 (p=0.05); and for DFS, N-stage (p<0.01), antigen A (p<0.01), Ki-67 (p=0.03), mucin (p=0.04) and T-stage (p=0.05). Of all the clinical-pathological, proliferative, and biological markers studied, only a few carried independent prognostic significance.

Analysis of neuroendocrine markers, HER2 and CEA before and after chemotherapy in patients with stage IIIA non-small cell lung cancer: a Cancer and Leukemia Group B study.

Several studies have suggested that biochemical or molecular markers examined in non-small cell lung cancer carry prognostic or treatment response information. Non-small cell lung cancer patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of HER2 (c-erbB-2), a membrane-bound receptor with tyrosine kinase activity, has been associated with shortened survival. The Cancer and Leukemia Group B (CALGB) performed a study of patients with stage IIIA (N2 nodes positive) non-small cell lung cancer in which patients received initial chemotherapy followed by surgery, then post-operative therapy consisting of sequential chemotherapy and radiation therapy. Since all patients underwent mediastinoscopy, this provided an opportunity to compare pre- and post-chemotherapy tumor specimens to test the hypothesis that these proteins would predict treatment response. In particular, we hypothesized that the post-chemotherapy specimens would be enriched for NE marker negative cells because of the increased sensitivity of NE positive cells to chemotherapy. We performed immunohistochemical analysis for a panel of NE markers [neuron-specific enolase (NSE), Leu-7, chromogranin A (ChrA), synaptophysin (Syn)], HER2 and CEA to determine if there was an effect of therapy on the percentage of cells expressing these markers. Secondary endpoints were a correlation with chemotherapy response and survival. Slides were scored for intensity (0-4) and percentage of cells positive (0-4). Of 61 eligible patients, there were 38 with both pre- and post-chemotherapy specimens. When both intensity of staining and percentage of positive cells were considered, post-chemotherapy specimens had a higher percentage of positive NE markers compared with pre-chemotherapy. In addition, there was no correlation between NE marker, HER2 or CEA expression (prior to or post treatment) and response to chemotherapy or survival. These data do not support the hypothesis that NE positive tumor cells are preferentially killed by chemotherapy in patients with stage IIIA non-small cell lung cancer.

Prognostic significance of Lewis y antigen in resected stage I and II non-small cell lung cancer.

BACKGROUND: The role of Lewis y (Le(y)) antigen expression has been studied extensively in predicting the outcome of various malignancies. We evaluated the expression of Le(y) and its relationship to survival, disease-free survival and other clinicopathologic variables in patients with stage I and II non-small cell lung cancer (NSCLC). OBJECTIVE: To investigate the prognostic significance of Le(y) antigen expression in a large group of well characterized patients with resected stage I and II NSCLC. PATIENTS: Two hundred and sixty patients with surgically resected stage I (n = 193) and II (n = 67) NSCLC with at least 5-year follow-up were identified. RESULTS: The median survival for patients with negative expression of Le(y) (< 50% of cells that were positive) was 46 months, whereas for those with positive expression of Le(y) (> or = 50%), the median survival was 54 months (p = 0.99). The disease-free survival for patients with Le(y)(-) expression was 39 months and 34 months for patients with Le(y)(+) expression (p = 0.3). CONCLUSIONS: We found no relationship between loss of blood group antigen A and expression of Le(y). No statistically significant difference was found in survival between positive and negative expression of Le(y) antigen in patients with resected stage I and II NSCLC.

Adenovirus infection of the renal allograft with sparing of pancreas graft function in the recipient of a combined kidney-pancreas transplant.

We report a case of adenovirus infection of the renal allograft in a combined kidney/pancreas transplant recipient. The clinical presentation was renal allograft failure, which eventually reversed. The pancreatic graft function remained stable. A renal biopsy showed massive tubular necrosis associated with a prominent granulomatous reaction. The process had a striking regional distribution within the kidney with the injury and inflammation limited to the outer medulla. Adenovirus type 11 was isolated from renal tissue by culture, and adenovirus was demonstrated by immunofluorescence and electron microscopy in the kidney biopsy. Immunosuppression may result in unusual patterns of response to infectious agents. This case demonstrated tropism of the adenovirus to only selected tubules within the kidney, with sparing of other organ function including, specifically, the pancreas allograft. The differential diagnosis of a granulomatous reaction in the transplant kidney must be expanded to include viral infection, in particular, adenovirus.

Blood group antigen A and flow cytometric analysis in resected early-stage non-small cell lung cancer.

The loss of blood group antigen A on tumor tissue has been reported to be a strong adverse prognostic marker for patients with resected non-small cell lung cancer (NSCLC). Results have varied with respect to the prognostic significance of flow cytometric data. We sought to confirm the prognostic significance of blood group antigen A loss and flow cytometry in a large cohort of patients with early-stage NSCLC. Two hundred and sixty patients with surgically resected stage I (n = 193) and II (n = 67) NSCLC with at least a 5-year follow-up were identified. Using paraffin-embedded primary tumor, immunohistochemical stains for blood group antigen A were performed on 90 patients with blood type A or AB. The DNA index and percentage of cells in S phase were successfully obtained on 188 and 152 patients, respectively. The median survival time of the patients with primary tumors negative for blood group antigen A was 38 months (n = 36), compared with 98 months (n = 54) for those with antigen A-positive tumors (P < 0.01). The median disease-free survival times for antigen A-negative and -positive tumors were 26 months and 98 months, respectively (P < h 0.01). The median survival time of the patients with aneuploid tumors was 51 months (n = 131), compared with 50 months (n = 57) for those with diploid tumors (P = 0.42). The median survival time of the patients with S phase >8% was 44 months (n = 105), compared with 60 months (n = 47) for those with S phase

IdLNF1-specific T cell clones accelerate the production of IdLNF1 + IgG and nephritis in SNF1 mice.

We have shown that antibodies bearing a nephritogenic idiotype (IdLNF1) are important in the pathogenesis of autoimmune glomerulonephritis in the (NZB x SWR)F1 hybrid, SNF1. A significant shift in the ratio of CD4+ to CD8+ IdLNF1-specific T lymphocytes, in favour of CD4+ IdLNF1-specific T cells, occurred at 22-24 weeks of age in the SNF1 and correlated with an increase in serum IdLNF1 + IgG and its deposition in the kidney. Recently, we reported the characteristics of six IdLNF1-specific T cell clones (CD3+CD4+CD8-V beta 17a+) derived from 22-week-old SNF1 mice which proliferated in response to IdLNF1 + Ig and augmented IdLNF1 + IgG production when mixed with SNF1 B cells in vitro. No increase in the production of anti-DNA antibodies was seen. Here we report results of the adoptive transfer of three of these clones, A1, B6 and D2, into 6-8-week-old SNF1 mice. Serum immunoglobulin (Ig) (IgG and IgM) levels did not differ from those of age-matched unmanipulated SNF1 up to and including 35 days post-injection. Similarly, total IdLNF1 + Ig levels did not vary significantly among the groups until 28 days post-injection. However, elevated levels of IdLNF1 + IgG were observed as early as 7 days post-injection in mice receiving clone B6 and 21 days post-injection in mice receiving clone D2. This was in sharp contrast with the results obtained in mice treated with clone A1 or unmanipulated SNF1 mice, which did not express IdLNF1 + IgG during this period. Digital image analysis of the kidney glomeruli of mice receiving T cell clones B6 or D2 demonstrated a significantly (P < 0.05) higher level of IdLNF1 + Ig deposition and glomerulonephritis than age-matched unmanipulated SNF1 mice or mice which had received clone A1. Interestingly, there was no statistically significant difference in the production of anti-ssDNA or dsDNA antibodies with the treatments. Mean survival for mice treated with T cell clones B6 and D2 was significantly (P < or = 1 x 10(-6)) shorter compared to unmanipulated SNF1 mice, while that of mice which had received T cell clone A1 was significantly (P < or = 3 x 10(-6)) longer, as determined by chi-squared analysis. The overall survival of mice treated with clones B6 and D2 did not differ from that of unmanipulated mice; however, mice treated with clone A1 survived significantly (P < or = 0.05) longer.(ABSTRACT TRUNCATED AT 400 WORDS)

False-positive antineutrophil cytoplasmic antibody in aspergillosis with oxalosis.

Although highly specific for Wegener's granulomatosis and other vasculitides, false-positive antineutrophil cytoplasmic antibody is occasionally encountered in other nonvasculitic conditions. We report a case of clinically suspected Wegener's granulomatosis with a large pulmonary cavity, renal failure, and positive cytoplasmic antineutrophil cytoplasmic antibody reaction. The patient died before initiation of immunosuppressive therapy. Postmortem examination revealed pulmonary aspergillosis due to Aspergillus niger, with extensive pulmonary and renal oxalosis, which lead to renal failure. The possible role of oxalosis in the pathogenesis of false-positive antineutrophil cytoplasmic antibody reaction is discussed.

Oligodendrocyte-specific expression and autoantigenicity of transaldolase in multiple sclerosis.

Although the etiology of multiple sclerosis (MS) is unknown, there is compelling evidence that its pathogenesis is mediated through the immune system. Molecular mimicry, i.e., crossreactivity between self-antigens and viral proteins, has been implicated in the initiation of autoimmunity and MS. Based on homology to human T cell lymphotropic virus type I (HTLV-I) a novel human retrotransposon was cloned and found to constitute an integral part of the coding sequence of the human transaldolase gene (TAL-H). TAL-H is a key enzyme of the nonoxidative pentose phosphate pathway (PPP) providing ribose-5-phosphate for nucleic acid synthesis and NADPH for lipid biosynthesis. Another fundamental function of the PPP is to maintain glutathione at a reduced state and, consequently, to protect sulfhydryl groups and cellular integrity from oxygen radicals. Immunohistochemical analyses of human brain sections and primary murine brain cell cultures demonstrated that TAL is expressed selectively in oligodendrocytes at high levels, possibly linked to production of large amounts of lipids as a major component of myelin, and to the protection of the vast network of myelin sheaths from oxygen radicals. High-affinity autoantibodies to recombinant TAL-H were detected in serum (25/87) and cerebrospinal fluid (15/20) of patients with MS. By contrast, TAL-H antibodies were absent in 145 normal individuals and patients with other autoimmune and neurological diseases. In addition, recombinant TAL-H stimulated proliferation and caused aggregate formation of peripheral blood lymphocytes from patients with MS. Remarkable amino acid sequence homologies were noted between TAL-H and core proteins of human retroviruses. Presence of crossreactive antigenic epitopes between recombinant TAL-H and HTLV-I/human immunodeficiency virus type 1 (HIV-1) gas proteins was demonstrated by Western blot analysis. The results suggest that molecular mimicry between viral core proteins and TAL-H may play a role in breaking immunological tolerance and leading to a selective destruction of oligodendrocytes in MS.

The prognostic significance of neuroendocrine markers and carcinoembryonic antigen in patients with resected stage I and II non-small cell lung cancer.

Non-small cell lung cancer with neuroendocrine differentiation may represent a subset of patients with a more aggressive (like small cell lung cancer) or less aggressive (like carcinoid) biological behavior. To investigate their prognostic significance, immunohistochemical stains for 4 neuroendocrine markers (neuron-specific enolase, chromogranin A, Leu-7, and synaptophysin) and carcinoembryonic antigen (CEA) were studied in 260 patients with surgically resected stage I and II non-small cell lung cancer. The following percentages of cases were positive for each marker: neuron-specific enolase, 70.0%; chromogranin A, 14.2%; Leu-7, 7.7%; synaptophysin, 11.2%; and CEA, 68.5%. Sixty-one (23.5%) were positive for > or = 2 neuroendocrine markers. When compared to adenocarcinoma, squamous cell carcinoma displayed lower positivity for CEA and > or = 2 neuroendocrine markers. There was no significant difference in stage, site of relapse (distant versus local), disease-free, or overall survival for each marker individually or for those with > or = 2 neuroendocrine markers. Multivariate analysis showed that higher nodal stage (N1 versus N0), tumor stage (T2 versus T1), older age, and the presence of mucin predicted for poorer overall survival. Neuroendocrine markers and CEA were not of prognostic significance in this group of patients with resected stage I and II non-small cell lung cancer.

Pleomorphic fibrohistiocytoma of the breast: a potential pitfall in breast biopsy interpretation.

We describe a benign mammary mesenchymal tumour with atypical stromal giant cells in the contralateral breast of a 66-year-old woman with infiltrating ductal carcinoma. The clinical, morphological and immunohistochemical features of this tumour suggest a pleomorphic variant of fibrous histiocytoma. This benign lesion represents a possible pitfall in breast pathology when interpreting a frozen section or fine needle aspiration biopsy.

erbB-2 and myc oncoproteins in sera and tumors of breast cancer patients.

This study compares the prevalence of elevated serological levels of erbB-2 and myc proteins in 36 breast cancer patients and 25 healthy, ambulatory female controls. The controls were frequency matched to the cases by age and ethnicity. Oncoprotein levels were determined blind to the "case-control status" of the individual from whom the specimen was derived. Corresponding tissue levels were examined in tumors of the 13 cases from whom sufficient tissue was available. Serum oncoproteins were elevated as follows: erbB-2 in one control (4%) compared with nine cases (25%; PFisher's exact = 0.03); myc in no control (0%) compared with seven cases (19%; PFisher's exact = 0.02). Elevated serum levels of erbB-2 or myc oncoproteins were detected in four of the seven cases (57.1%) of in situ cancer without evidence of infiltration. In all cases with elevated serum oncoproteins where tumor tissue was available, the corresponding protein was elevated in the tumor. The three cases who had elevated preoperative serum oncoprotein levels and from whom it was possible to procure postoperative specimens had normal postoperative serum oncoprotein levels. We conclude that (a) erbB-2 and myc oncoproteins are elevated in a proportion of breast cancer patients, (b) the tumor seems to be the source of the serum elevation, and (c) these proteins may be useful as part of a panel of biomarkers of early malignant disease.

Localization of basic fibroblast growth factor and vascular endothelial growth factor in human glial neoplasms.

Fibroblast growth factors (FGFs) are widely recognized as a family of molecules that can influence cell proliferation and tissue neovascularization. Although the basic form of FGF (bFGF) has been found to enhance the growth of primary cell cultures made from human glial tumors, its exact role in vivo has been unclear. Likewise, vascular endothelial growth factor (VEGF) is a newly discovered addition to the growing list of angiogenic factors but, unlike bFGF, VEGF has a unique specificity for endothelial cells and possesses the properties required for secretion. In this study, we localized both basic FGF and VEGF in human gliomas to assess their possible role in the pathogenesis of these neoplasms. Retrospective analysis was performed using glial neoplasms that were fixed in 10% neutral buffered formalin and embedded in paraffin. The immunocytochemical procedures were performed using specific polyclonal antibodies raised against the amino terminus of bFGF and VEGF, respectively. Immunoreactive (IR) basic FGF was localized in normal, reactive, and neoplastic astrocytes as well as selected populations of normal neurons. IR VEGF, in contrast, was present primarily in neurons of normal brain, but was also found in both reactive and neoplastic astrocytes. In adjacent 4-microns tissue sections, strong immunoreactivity for VEGF and bFGF was found within the same populations of cells. In areas of endothelial proliferation, the strongest immunoreactivity for both growth factors was found within large anaplastic astrocytes that surrounded abnormal blood vessels. Our data support the hypothesis that VEGF may complement the actions of basic FGF in glial neoplasia.