Generalizing the Value of Ongoing Assessments of Suicidal Ideation or Behavior for Estimating the Risk of Subsequent Suicide Attempts.

In analyses conducted for program planning, the Veterans Health Administration evaluated associations between self-reports of suicidal ideation and behavior using the Columbia Scale obtained on two occasions separated by three months and clinical or administrative records of suicide attempts over the subsequent three months., Combining information from the two assessments improved prediction of suicidal behavior and found that risk was greater when ideation was reported on both assessments, than when it was first reported at follow-up. The absence of reported ideation at the second assessment was not associated with a clinically relevant reduction in risk. These findings confirm recent reports from the Mental Health Research Network (MHRN).

Assessment of Rates of Suicide Risk Screening and Prevalence of Positive Screening Results Among US Veterans After Implementation of the Veterans Affairs Suicide Risk Identification Strategy.

Importance: In 2018, the Veterans Health Administration (VHA) implemented the Veterans Affairs (VA) Suicide Risk Identification Strategy to improve the identification and management of suicide risk among veterans receiving VHA care. Objectives: To examine the prevalence of positive suicide screening results among veterans in ambulatory care and emergency departments (EDs) or urgent care clinics (UCCs) and to compare acuity of suicide risk among patients screened in these settings. Design, Setting, and Participants: This cross-sectional study used data from the VA's Corporate Data Warehouse (CDW) to assess veterans with at least 1 ambulatory care visit (n = 4 101 685) or ED or UCC visit (n = 1 044 056) at 140 VHA medical centers from October 1, 2018, through September 30, 2019. Exposures: Standardized suicide risk screening and evaluation tools. Main Outcomes and Measures: One-year rate of suicide risk screening and evaluation, prevalence of positive primary and secondary suicide risk screening results, and levels of acute and chronic risk based on the VHA's Comprehensive Suicide Risk Evaluation. Results: A total of 4 101 685 veterans in ambulatory care settings (mean [SD] age, 62.3 [16.4] years; 3 771 379 [91.9%] male; 2 996 974 [73.1%] White) and 1 044 056 veterans in ED or UCC settings (mean [SD] age, 59.2 [16.2] years; 932 319 [89.3%] male; 688 559 [66.0%] White) received the primary suicide screening. The prevalence of positive suicide screening results was 3.5% for primary screening and 0.4% for secondary screening in ambulatory care and 3.6% for primary screening and 2.1% in secondary screening for ED and UCC settings. Compared with veterans screened in ambulatory care, those screened in the ED or UCC were more likely to endorse suicidal ideation with intent (odds ratio [OR], 4.55; 95% CI, 4.37-4.74; P < .001), specific plan (OR, 3.16; 95% CI, 3.04-3.29; P < .001), and recent suicidal behavior (OR, 1.95; 95% CI, 1.87-2.03; P < .001) during secondary screening. Among the patients who received a Comprehensive Suicide Risk Evaluation, those in ED or UCC settings were more likely than those in ambulatory care settings to be at high acute risk (34.1% vs 8.5%; P < .001). Conclusions and Relevance: In this cross-sectional study, population-based suicide risk screening and evaluation in VHA ambulatory care and ED or UCC settings may help identify risk among patients who may not be receiving mental health treatment. Higher acuity of risk among veterans in ED or UCC settings compared with those in ambulatory care settings highlights the importance of scaling up implementation of brief evidence-based interventions in the ED or UCC to reduce suicidal behavior.

Protocol: examining the effectiveness of an adaptive implementation intervention to improve uptake of the VA suicide risk identification strategy: a sequential multiple assignment randomized trial.

BACKGROUND: In 2018, the Veterans Health Administration (VHA) mandated implementation of a national suicide risk identification strategy (Risk ID). The goal of Risk ID is to improve the detection and management of suicide risk by standardizing suicide risk screening and evaluation enterprise-wide. In order to ensure continuous quality improvement (QI), ongoing evaluation and targeted interventions to improve implementation of Risk ID are needed. Moreover, given that facilities will vary with respect to implementation needs and barriers, the dose and type of intervention needed may vary across facilities. Thus, the objective of this study is to examine the effectiveness of an adaptive implementation strategy to improve the uptake of suicide risk screening and evaluation in VHA ambulatory care settings. In addition, this study will examine specific factors that may impact the uptake of suicide risk screening and evaluation and the adoption of different implementation strategies. This protocol describes the stepped implementation approach and proposed evaluation plan. METHODS: Using a sequential multiple assignment randomized trial (SMART) design, two evidence-based implementation strategies will be evaluated: (1) audit and feedback (A&F); (2) A&F plus external facilitation (A&F + EF). Implementation outcomes of interest include uptake of secondary suicide risk screening and uptake of comprehensive suicide risk evaluation (stages 2 and 3 of Risk ID). Secondary outcomes include rates of other clinical outcomes (i.e., safety planning) and organizational factors that may impact Risk ID implementation (i.e., leadership climate and leadership support). DISCUSSION: This national QI study will use a SMART design to evaluate whether an adaptive implementation strategy is effective in improving uptake of a mandated VHA-wide suicide risk screening and evaluation initiative. If this study finds that the proposed stepped implementation strategy is effective at increasing uptake and maintaining performance improvements, this approach may be used as an overarching QI strategy for other national suicide prevention programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04243330 . Registered 28 January 2020.

Use of the Columbia-Suicide Severity Rating Scale (C-SSRS) in a large sample of Veterans receiving mental health services in the Veterans Health Administration.

OBJECTIVE: To evaluate the associations of self-reports of suicidal ideation and behavior using the Columbia-Suicide Severity Rating Scale (C-SSRS) in a survey of patients receiving mental health services in the Veterans Health Administration (VHA) with reports of attempts documented in medical records and administrative data. METHOD: The C-SSRS was administered to 15,373 Veterans in the Veterans Outcome Assessment (VOA) survey. Concurrent validity was evaluated by comparing self-reports from the past 3 months with VHA records. Predictive validity was evaluated by logistic regression models using attempts over the subsequent 3 months as the outcome. RESULTS: Tests of concurrent validity found strong associations between self-reports and attempts documented in VHA records, but there were substantial numbers of discordant responses. In tests of predictive validity, area under the ROC curve for predicting future attempts was >0.8. There were differences in the distribution of responses and of psychometric properties across VHA mental health programs. CONCLUSIONS: Findings support the value of screening and the validity of the self-reports based on the C-SSRS, but limitations in concordance with medical records and variability across programs suggest the need for clinical judgment in interpreting responses.

Microphthalmia-associated transcription factor (MiTF): Promiscuous staining patterns in fibrohistiocytic lesions is a potential pitfall.

Microphthalmia-associated transcription factor (MiTF) is used as a marker of melanocytic differentiation. However, MiTF immunoexpression has also been observed in histiocytes, macrophages, smooth muscle cells and fibroblasts, which raise the concern of fibrohistiocytic (FH) lesions being misdiagnosed as melanoma based on MiTF immunoreactivity. MiTF has been known to be positive in FH tumors, but this is the first study evaluating ninety-three fibrohistiocytic neoplasms to understand and delineate the staining pattern of MiTF in these tumors. Ninety-three cases of FH, 30 cases of melanocytic lesions, and 20 miscellaneous cases were studied. The FH cases included benign fibrous histiocytoma (BFH, n = 29), angiofibroma (AF, n = 11), fibromatosis (FM, n = 14), keloid (KE, n = 10), atypical fibroxanthoma (AFX, n = 7), dermal scar (DS, n = 9), dermatofibrosarcoma protuberans (DFSP, n = 12), and pigmented DFSP (Bednar tumor, n = 1). Benign fibrous histiocytoma were sub-categorized into dermatofibroma (n = 15) and epithelioid fibrous histiocytoma (n = 14). The melanocytic lesions included desmoplastic melanoma (DM, n = 8), melanoma in-situ (MIS, n = 5), re-excision-free of melanoma (RFM, n = 10), blue nevus (BN, n = 5), and spitz nevus (SN, n = 3). The miscellaneous category included osteosarcoma (OS, n = 3), pigmented basal cell carcinoma (PBCC, n = 5), spindle cell squamous cell carcinoma (SCA, n = 2), and giant cell tumor of tendon sheath (GCTTS, n = 10). All BFH, AF, AFX, KE, and DS cases showed a positive MiTF staining of variable extent and intensity. MiTF positivity was observed in 86% (n = 12) cases of FM and 17% (n = 2) cases of DFSP. Amongst the miscellaneous category, all cases of PBCC and GCTTS and 50% (n = 1) cases of SCA were immunoreactive for MiTF. All melanocytic lesions were positive for MiTF. None of the OS and pigmented DFSP showed positive labeling. Because of the promiscuity of MiTF labeling, awareness of its pattern in FH proliferations may avoid potential pitfalls in the diagnosis of spindle cell lesions.

The Real-World Effect of Intravitreous Anti-Vascular Endothelial Growth Factor Drugs on Intraocular Pressure: An Analysis Using the IRIS Registry.

PURPOSE: To identify sustained differences in intraocular pressure (IOP) after intravitreous injections of anti-vascular endothelial growth factor (VEGF) drugs. DESIGN: Database study. PARTICIPANTS: Patients seeing an ophthalmic provider who contributes to the database. METHODS: We identified a total of 23 776 unique patients who received only a single type of anti-VEGF medication (bevacizumab, aflibercept, or ranibizumab) by injection in the right eye in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Subgroups included patients with age-related macular degeneration only and patients who had not received an anti-VEGF injection for at least 1 year before the study. We examined those with at least 12, 18, and 25 injections for each of these 3 medications. For all groups, we used fellow, untreated eyes for comparison. MAIN OUTCOME MEASURES: The mean change in IOP from baseline at a minimum of 1 year of follow-up and the proportion of eyes with a clinically significant IOP increase (defined as sustained rise of at least 6 mmHg to an IOP of more than 21 mmHg). RESULTS: All patients in all groups receiving all drugs showed a decrease in IOP from baseline, with a mean of 0.9 mmHg in treated eyes compared with an average decrease of 0.2 mmHg in fellow untreated eyes, a statistically significant difference. A generalized linear model accounting for confounders associated bevacizumab with slightly less lowering of IOP than aflibercept and ranibizumab in most subgroups. A clinically significant IOP increase was seen in 2.6% of eyes receiving injections compared with 1.5% in the associated untreated fellow eyes. Clinically significant IOP increases occurred at a rate of 1.9%, 2.8%, and 2.8% for aflibercept, ranibizumab, and bevacizumab, respectively, which was significantly higher than untreated fellow eyes for bevacizumab and ranibizumab, but not for aflibercept. CONCLUSIONS: These analyses from real-world data indicate that anti-VEGF intravitreous injections are associated with a small but statistically significant decrease in IOP over time. A proportion of patients, on average 2.6%, experienced a sustained clinically significant IOP rise with these drugs overall compared with 1.5% in the fellow untreated eyes. However, such an increase was not seen with aflibercept.

Innovating team-based outpatient mental health care in the Veterans Health Administration: Staff-perceived benefits and challenges to pilot implementation of the Behavioral Health Interdisciplinary Program (BHIP).

In the past decade, the demand for Veterans Health Administration (VHA) mental health care has increased rapidly. In response to the increased demand, the VHA developed the Behavioral Health Interdisciplinary Program (BHIP) team model as an innovative approach to transform VHA general outpatient mental health delivery. The present formative evaluation gathered information about pilot implementation of BHIP to understand the struggles and successes that staff experienced during facility transitions to the BHIP model. Using a purposive, nonrandom sampling approach, we conducted 1-on-1, semistructured interviews with 37 licensed and nonlicensed clinical providers and 13 clerical support staff assigned to BHIP teams in 21 facilities across the VHA. Interviews revealed that having actively involved facility mental health leaders, obtaining adequate staffing for teams to meet the requirements of the BHIP model, creating clear descriptions and expectations for team member roles within the BHIP framework, and allocating designated time for BHIP team meetings challenged many VHA sites but are crucial for successful BHIP implementation. Despite the challenges, staff reported that the transition to BHIP improved team work and improved patient care. Staff specifically highlighted the potential for the BHIP model to improve staff working relationships and enhance communication, collaboration, morale, and veteran treatment consistency. Future evaluations of the BHIP implementation process and BHIP team functioning focusing on patient outcomes, organizational outcomes, and staff functioning are recommended for fully understanding effects of transitioning to the BHIP model within VHA general mental health clinics and to identify best practices and areas for improvement. (PsycINFO Database Record

Commutability of Cytomegalovirus WHO International Standard in Different Matrices.

Commutability of quantitative standards allows patient results to be compared across molecular diagnostic methods and laboratories. This is critical to establishing quantitative thresholds for use in clinical decision-making. A matrix effect associated with the 1st cytomegalovirus (CMV) WHO international standard (IS) was identified using the Abbott RealTime CMV assay. A commutability study was performed to compare the CMV WHO IS and patient specimens diluted in plasma and whole blood. Patient specimens showed similar CMV DNA quantitation values regardless of the diluent or extraction procedure used. The CMV WHO IS, on the other hand, exhibited a matrix effect. The CMV concentration reported for the WHO IS diluted in plasma was within the 95% prediction interval established with patient samples. In contrast, the reported DNA concentration of the CMV WHO IS diluted in whole blood was reduced approximately 0.4 log copies/ml, and values fell outside the 95% prediction interval. Calibrating the assay by using the CMV WHO IS diluted in whole blood would introduce a bias for CMV whole-blood quantitation; samples would be reported as having higher measured concentrations, by approximately 0.4 log IU/ml. Based on the commutability study with patient samples, the RealTime CMV assay was standardized based on the CMV WHO IS diluted in plasma. A revision of the instructions for use of the CMV WHO IS should be considered to alert users of the potential impact from the diluent matrix. The identification of a matrix effect with the CMV WHO IS underscores the importance of assessing commutability of the IS in order to achieve consistent results across methods.

Progestins inhibit calcitriol-induced CYP24A1 and synergistically inhibit ovarian cancer cell viability: An opportunity for chemoprevention.

OBJECTIVES: Previously we have shown in endometrial cells that progesterone (P4) and calcitriol (CAL, 1,25(OH)2D3) synergistically promote apoptosis and that progestins induce expression of the vitamin D receptor. In the current study we examined the progestin/vitamin D combination in ovarian cells and searched for other progestin-related effects on vitamin D metabolism that may underlie the novel interaction between progestins and vitamin D, including whether progestins inhibit CYP24A1, the enzyme that renders CAL inactive. METHODS: We investigated the impact of P4 on CAL-induced CYP24A1 expression in cancer cell lines expressing progesterone receptors (PRs), [OVCAR-5, OVCAR-3-PGR (PR-transfected OVCAR-3 ovarian line), and T47D-WT, T47D-A and T47D-B (breast lines expressing PRs or individual PR isoforms)] or lines that do not express PRs (OVCAR-3 and T47D-Y). We examined CYP24A1 expression using RT-PCR and western blotting, and apoptosis by TUNEL. We also investigated P4 inhibition of Cyp24a1 in ovaries from CAL-treated mice. RESULTS: CAL treatment induced CYP24A1 expression. When co-treated with P4, cell lines expressing PRs showed marked inhibition of CYP24A1 expression (p<0.001), along with increased apoptosis (p<0.01); cells not expressing PRs did not. Mouse ovaries showed a significant reduction in CAL-induced Cyp24a1 mRNA (p<0.001) and protein (p<0.01) in response to P4. CONCLUSIONS: We show for the first time that progestins and vitamin D synergistically reduce cell viability and induce apoptosis in ovarian cells and that progestins PR-dependently inhibit CAL-induced CYP24A1, thus extending CAL activity. The combination of progestins and vitamin D deserves further consideration as a strategy for inhibiting ovarian carcinogenesis.

Reticulin and NM23 staining in the interpretation of lymph nodal nevus rests.

Melanocytic nevus rests in lymph nodes are a known diagnostic challenge, especially in patients with a history of melanoma. Reticulin and NM23 have been studied in this context. The pattern of reticulin staining in melanomas surrounds groups/nests of melanocytes but individual cells in benign nevi. NM23, a metastasis-suppressor gene, has an association with metastatic potential in melanomas and some carcinomas. Twenty-eight cases (14 cases of metastatic melanoma to lymph nodes and 14 cases of lymph node nevus rests, all confirmed with Melan-A staining) were stained with reticulin and NM23. The pattern of reticulin staining was reported as surrounding groups if staining was noted in approximately 5-10 melanocytes in greater than 50% of the lesion but was otherwise reported as surrounding individual melanocytes. Cytoplasmic staining was considered to represent reactivity for NM23. Reticulin staining around groups of melanocytes was identified in all 14 cases of metastatic melanoma. Regarding nodal nevus rest cases, 12 of 14 cases (86%) demonstrated staining around individual melanocytes, whereas in 2 cases, reticulin surrounded melanocytic groups. NM23 staining was equivocal in all cases. Reticulin staining reliably invests groups of melanocytes in cases of metastatic melanoma, whereas in nodal nevus rests, it predominantly surrounds individual melanocytes. NM23 demonstrated no discriminatory value in this analysis. In cases in which a collection of melanocytes is present within a lymph node, reticulin deposition around individual melanocytes supports a diagnosis of lymph nodal nevus rest.

Nevic mitoses: a review of 1041 cases.

The presence of dermal mitotic figures is helpful in identifying malignant melanocytic lesions but occasionally occur in benign nevi. We aim to determine a "benchmark" mitotic frequency for a wide variety of nevi. We prospectively collected 1041 cases of benign melanocytic nevi and reviewed them for the presence of mitotic figures. Specimens were collected from female (62%) and male (38%) participants, ages ranged from 1 to 90 years. Nevus types included compound melanocytic nevi (CMN), intradermal melanocytic nevi, junctional melanocytic nevi, lentiginous CMN (LCMN), lentiginous junctional melanocytic nevi, blue nevi, deep penetrating nevi, and pigmented spindle cell nevi. Nevi with congenital, mildly dysplastic, and Spitzoid features were included. A total of 82 of 1041 (7.9%) nevi contained one or more mitotic figures. Most (76.1%) mitoses were found in the papillary dermis. Single mitotic figures were more common (80.4%) than 2 (15.9%) or 3 (3.7%) within a single specimen. Of all cases containing mitotic figures, the most common nevus type was CMN. The nevus type most frequently demonstrating mitotic figures was CMN. The most common body site among cases with mitotic figures was trunk (53.7%), whereas the body site with the largest proportion of nevi demonstrating mitotic figures was special site (10.9%). The percentage of nevi containing mitotic figures was nearly the same among female (7.9%) and male (7.8%) participants. Results of this large review confirm that mitotic figures, even multiple ones, do not preclude benignity in a variety of melanocytic nevi.

Master's programs in advanced nursing practice: new strategies to enhance course design for subspecialty training in neonatology and pediatrics.

The advanced nurse practitioner (ANP) role first developed in the USA in the 1960s in primary care. Since then, it has evolved in many different countries and subspecialties, creating a variety of challenges for those designing and implementing master's programs for this valuable professional group. We focus on ANPs in the neonatal and pediatric intensive care setting to illustrate the complexity of issues faced by both faculty and students in such a program. We review the impact of limited resources, faculty recruitment/accreditation, and the relationship with the medical profession in establishing a curriculum. We explore the evidence for the importance of ANP role definition, supervision, and identity among other health professionals to secure a successful role transition. We describe how recent advances in technology can be used to innovate with new styles of teaching and learning to overcome some of the difficulties in running master's programs for small subspecialties. We illustrate, through our own experience, how a thorough assessment of the available literature can be used to innovate and develop strategies to create an individual MSc programs that are designed to meet the needs of highly specialized advanced neonatal and pediatric nursing practice.

Nonsteroidal antiinflammatory drugs and progestins synergistically enhance cell death in ovarian epithelial cells.

OBJECTIVE: There is growing evidence that progestins and nonsteroidal antiinflammatory drugs (NSAIDs) may prevent ovarian cancer. Because both induce apoptosis, we investigated the potential for synergistic impact of combined drug treatment on cell death. STUDY DESIGN: Using normal and malignant human ovarian epithelial cells and an NSAID-sensitive human colon cancer cell line, we evaluated the effects of progestins and NSAIDs alone and in combination on apoptosis. RESULTS: Both progestins and NSAIDs dose dependently inhibited cell growth (P < .0001). Doses of NSAIDs or progestins that independently reduced cell viability by less than 30% synergistically reduced cell viability by 70-95% when combined. Similarly, the NSAID/progestin combination conferred 4- to 18-fold (P < .05) increased apoptosis over either treatment alone. CONCLUSION: Our results suggest it may be possible to combine progestins and NSAIDs to achieve ovarian cancer prevention at lower doses of each than are required for single administration, thereby lessening the risk of side effects posed by these agents.

Multicentric reticulohistiocytosis and urologic carcinomas: a possible paraneoplastic association.

Multicentric reticulohistiocytosis (MR) is a rare non-Langerhans histiocytosis that is characterized by cutaneous nodules and severe destructive arthritis. Although 25-30% of reported cases have been associated with internal malignancies, the pathophysiology of MR is unknown. Herein, we report two cases of MR that were associated with urologic neoplasms. Because the tumor suppressor gene p53 may play a role in the biology of other histiocytoses, we investigated its p53 immunoexpression in these two cases. Both cases were positive immunohistochemically, but it remains to be seen whether this finding is truly important in the pathogenesis of MR associated with underlying visceral neoplasms.

Cutaneous T-cell lymphoma occurring with a melanocytic proliferation, masquerading as a nonhealing ulcer with reactive changes.

Two of the most challenging areas in dermatopathology are lymphoproliferative disorders and melanocytic lesions. We present a case of peripheral T-cell lymphoma occurring with an intradermal melanocytic proliferation. A 63-year-old Caucasian man presented with a 12-cm edematous, erythematous to violaceous, scalp ulceration that had enlarged over six months. Previous biopsies showed reactive changes which were concerning for infection. The last biopsies showed small to intermediate sized, angulated cells with clear cytoplasm within the dermis, with extension into the epidermis. These cells stained positive with markers for CD3, CD45RO and CD43, yet showed decreased expression of pan-T-cell markers CD5 and CD7, and absent expression of CD4, CD8, CD56 and CD57 and EBV. Molecular studies showed a clonal T-cell receptor gamma chain gene rearrangement. The diagnosis was peripheral T-cell lymphoma, unspecified. Another biopsy from an indurated area separate from the ulcer showed scattered, enlarged cells embedded in the same lymphocytic infiltrate. No mitotic figures were identified. These cells stained for S100 and Melan-A, in a partly nested arrangement. This was felt to represent a melanocytic nevus. This case likely represents an extraordinary coincidence of two distinctly different neoplasms.

Diffuse dermal angiomatosis associated with calciphylaxis.

Diffuse dermal angiomatosis (DDA) is a reactive proliferation of vascular channels within the dermis often associated with atherosclerosis. Based on our observation of a case of calciphylaxis (CP) with extensive DDA, we investigated a new possible association and incidence of DDA in patients with CP. These 2 rare conditions had not been reported previously in the same patient. In a retrospective review of skin biopsies taken between 1988 and 2006, 11 patients with histologically proven CP were identified and the medical records were reviewed. Two cases were excluded due to inadequate specimens for a thorough histologic evaluation. Nine patients with large necrotic plaques/ulcers were included in the study. Associated diseases were end-stage renal insufficiency (n = 7), parathyroidectomy for hyperparathyroidism (n = 3), thromboembolic events (n = 3), hypertension (n = 3), and diabetes mellitus (n = 2). Histologically, all cases had some degree of diffuse dermal proliferation of vascular channels with interstitial expression of CD31, as well as subcutaneous fat necrosis and calcification with medial vascular calcification. The extent of DDA did not correlate with the gravity or severity of disease. Based on our observation, DDA is a common histological finding encountered in the dermis adjacent to necrotizing ulcers in patients with CP.

Dysregulation of CXCL9 and reduced tumor growth in Egr-1 deficient mice.

BACKGROUND: Early growth response-1 (Egr-1) is an immediate-early transcription factor inducible in the vasculature in response to injury, shear stress, and other stimuli. Mice lacking Egr-1 have a profound deficit in the ability to recover from femoral artery ligation, suggesting a role in neovascularization. Previous studies have shown that manipulating Egr-1 expression can have either positive or negative effects on tumor growth. We hypothesized that Egr-1 knockout mice might exhibit reduced tumor growth, possibly due to a reduced capacity to respond to angiogenic signals from a growing tumor. RESULTS: We injected 106 Lewis lung carcinoma (LLC1) cells subcutaneously in the flank of wild type and Egr-1 knockout mice. The average mass of tumors from wild type mice at 12 days after implantation was 413 +/- 128 mg, while those from Egr-1-/- mice was 219 +/- 81 mg (p = 0.001, mean +/- SD). However, sectioning the tumors and staining with anti-CD31 antibodies revealed no difference in the vascularity of the tumors and there was no difference in angiogenic growth factor expression. Expression of the chemokine Mig (CXCL9) was increased 2.8-fold in tumors from knockout mice, but no increase was found in serum levels of Mig. Natural killer cells have a 1.7-fold greater prevalence in the CD45+ cells found in tumors from Egr-1-/- mice compared to those from wild type mice. Immunohistochemical staining suggests that Mig expression in the tumors comes from invading macrophages. CONCLUSION: Mice deficient in Egr-1 exhibit reduced growth of LLC1 tumors, and this phenomenon is associated with overexpression of Mig locally within the tumor. There are no obvious differences in tumor vascularity in the knockout mice. Natural killer cells accumulate in the tumors grown in Egr-1-/- mice, providing a potential mechanism for the reduction in growth.

Ovarian adenocarcinomas in the laying hen and women share similar alterations in p53, ras, and HER-2/neu.

We examined alterations in the p53 tumor suppressor gene and the ras and HER-2/neu oncogenes in chicken ovarian cancers to determine if these tumors have genetic alterations similar to those in human ovarian adenocarcinomas. Mutations in the p53 tumor suppressor gene and the H-ras and K-ras oncogenes were assessed by direct sequencing in 172 ovarian cancers obtained from 4-year-old birds enrolled at age 2 in two separate 2-year chemoprevention trials. Birds in trial B had approximately twice as many lifetime ovulations as those in trial A. Immunohistochemical staining for the HER-2/neu oncogene was done on a subset of avian ovarian and oviductal adenocarcinomas. Alterations in p53 were detected in 48% of chicken ovarian cancers. Incidence of p53 alterations varied according to the number of lifetime ovulations, ranging from 14% in trial A to 96% in trial B (P < 0.01). No mutations were seen in H-ras, and only 2 of 172 (1.2%) tumors had K-ras mutations. Significant HER-2/neu staining was noted in 10 of 19 ovarian adenocarcinomas but in only 1 of 17 oviductal adenocarcinomas. Similar to human ovarian cancers, p53 alterations are common in chicken ovarian adenocarcinomas and correlate with the number of lifetime ovulations. Ras mutations are rare, similar to high-grade human ovarian cancers. HER-2/neu overexpression is common and may represent a marker to exclude an oviductal origin in cancers involving both the ovary and oviduct.