[Show abstract][Hide abstract] ABSTRACT: Background
Matrix metalloproteinase-23 (MMP-23) can block the voltage-gated potassium channel Kv1.3, whose function is important for sustained Ca2+ signaling during T cell activation. MMP-23 may also alter T cell activity and phenotype through cleavage of proteins affecting cytokine and chemokine signaling. We therefore tested the hypothesis that MMP-23 can negatively regulate the anti-tumor T cell response in human melanoma.Methods
We characterized MMP-23 expression in primary melanoma patients who received adjuvant immunotherapy. We examined the association of MMP-23 with the anti-tumor immune response - as assessed by the prevalence of tumor-infiltrating lymphocytes and Foxp3+ regulatory T cells. Further, we examined the association between MMP-23 expression and response to immunotherapy. Considering also an in trans mechanism, we examined the association of melanoma MMP-23 and melanoma Kv1.3 expression.ResultsOur data revealed an inverse association between primary melanoma MMP-23 expression and the anti-tumor T cell response, as demonstrated by decreased tumor-infiltrating lymphocytes (TIL) (P¿=¿0.05), in particular brisk TILs (P¿=¿0.04), and a trend towards an increased proportion of immunosuppressive Foxp3+ regulatory T cells (P¿=¿0.07). High melanoma MMP-23 expression is also associated with recurrence in patients treated with immune biologics (P¿=¿0.037) but not in those treated with vaccines (P¿=¿0.64). Further, high melanoma MMP-23 expression is associated with shorter periods of progression-free survival for patients receiving immune biologics (P¿=¿0.025). On the other hand, there is no relationship between melanoma MMP-23 and melanoma Kv1.3 expression (P¿=¿0.27).Conclusions
Our data support a role for MMP-23 as a potential immunosuppressive target in melanoma, as well as a possible biomarker for informing melanoma immunotherapies.
Journal of Translational Medicine 12/2014; 12(1):342. · 3.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Single nucleotide polymorphisms (SNPs) in platelet-associated genes partly explain inherent variability in platelet counts. Patients with monoallelic Bernard Soulier syndrome due to the Bolzano mutation (GPIBA A156V) have variable platelet counts despite a common mutation for unknown reasons.Objectives
We investigated the effect of the most common SNP (R307H) in the hematopoietic-specific tubulin isotype β-1 in these Bernard Soulier patients and potential microtubule-based mechanisms of worsened thrombocytopenia.Patients/Methods
Ninety-four monoallelic Bolzano mutation patients were evaluated for the R307H β-1 SNP and had platelet counts measured by three methods; the Q43P SNP was also evaluated. To investigate possible mechanisms underlying this association, we used molecular modeling of β-1 tubulin with and without the R307H SNP. We transfected SNP or non-SNP β-1 tubulin into MCF-7 and CMK cell lines and measured microtubule regrowth after nocodazole-induced depolymerization.ResultsWe found that patients with at least one R307H SNP allele had significantly worse thrombocytopenia; manual platelet counting revealed a median platelet count of 124 in non-SNP and 76 in SNP patients (both x 109/L; p<0.01). The Q43P SNP had no significant association with platelet count. Molecular modeling suggested a structural relationship between the R307H SNP and microtubule stability via alterations in the M-loop of β tubulin; in vitro microtubule recovery assays revealed cells transfected with R307H SNP β-1 had significantly impaired microtubule recovery.Conclusions
Our data show that the R307H SNP is significantly associated with the degree of thrombocytopenia in congenital and acquired platelet disorders, and may affect platelets by altering microtubule behavior.This article is protected by copyright. All rights reserved.
Journal of Thrombosis and Haemostasis 12/2014; · 6.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Author Summary BACKGROUND: Transcatheter arterial chemoembolization (TACE) has been used to curtail tumor vasculature and delay tumor progression in hepatocellular carcinoma (HCC). We conducted a phase I trial to evaluate the efficacy and toxicity of thalidomide when combined with TACE in patients with advanced HCC.
[Show abstract][Hide abstract] ABSTRACT: Studies have shown that older women are undertreated for breast cancer. Few data are available on cancer-related death in elderly women aged 70 years and older with pathologic stage T1a-b N0 breast cancer and the impact of prognostic factors on cancer-related death.
[Show abstract][Hide abstract] ABSTRACT: Background
Adult respiratory distress syndrome (ARDS) has a high mortality rate and consumes considerable health care resources. It is not clear whether specimens obtained from open lung biopsy (OLB) in ARDS provide a specific diagnosis, alter therapy, or affect outcome. This meta-analysis attempts to determine whether OLB is safe, provides a specific diagnosis, changes therapy, or affects survival.
A computerized search was performed of Medline and PubMed from January 1988 to December 2012 of English language studies of acute respiratory failure and diffuse pulmonary infiltrates that evaluated OLB in primarily adult mechanically ventilated patients. Of 194 abstracts retrieved, 64 articles were reviewed; 130 articles were excluded because they did not evaluate OLB. After applying the selection criteria, 24 articles were included.
OLB in ARDS provided a specific diagnosis in 84% of patients and altered management in 73%. Hospital mortality was 43%. The complication rate for OLB in ARDS was 22%, but death from OLB was rare.
OLB in ARDS is a potentially productive procedure that provides a specific diagnosis and leads to a change in management in high proportions of patients. ARDS has a high mortality rate, which OLB does not appear to increase. Owing to a lack of randomized controlled trials, a survival advantage of OLB in ARDS could not be demonstrated.
The Annals of Thoracic Surgery 10/2014; · 3.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:In severe obesity, impairments in health-related quality of life (HRQoL) and dysphoric mood are reported. This is a post-surgery analysis of the relationship between HRQoL and depressive symptoms, and weight change after four different types of bariatric procedures.Methods:A total of 105 consented patients completed the Short-Form-36 Health Survey (SF-36), the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) and the Beck Depression Inventory (BDI) before and 25 months after surgery. Analysis of variance or Kruskal-Wallis test evaluated changes.Results:Patients with Roux-en Y gastric bypass (46 patients), decreased body mass indexes (BMIs; kg m(-)(2)) 47-31 kg m(-)(2) (P<0.0001); biliopancreatic diversion with duodenal switch (18 patients), decreased BMIs 57-30 kg m(-)(2) (P<0.0001); adjustable gastric banding (18 patients), decreased BMIs 45-38 kg m(-)(2) (P<0.0001); and sleeve gastrectomies (23 patients), decreased BMIs 58 42 kg m(-)(2) (P<0.0001). The excess percentage BMI loss was 69, 89, 36 and 53 kg m(-)(2), respectively (P<0.0001). Before surgery, the SF-36 differences were significant regarding bodily pain (P=0.008) and social functioning (P=0.01). After surgery, physical function (P=0.03), general health (P=0.05) and physical component (P=0.03) were different. IWQOL-Lite recorded no differences until after surgery: physical function (P=0.003), sexual life (P=0.04) and public distress (P=0.003). BDI scores were not different for the four groups at baseline. All improved with surgery, 10.6-4.4 (P=0.0001).Conclusions:HRQoL and depressive symptoms significantly improvement after surgery. These improvements do not have a differential effect over the wide range of weight change.Nutrition & Diabetes (2014) 4, e132; doi:10.1038/nutd.2014.29; published online 1 September 2014.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to determine if a significant difference exists in the nasolacrimal duct volume of subjects with primary nasolacrimal duct obstruction compared with that of controls.
Ophthalmic Plastic and Reconstructive Surgery 08/2014; · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
/Background: With improved breast cancer (BC) screening and treatment, the risk for long term toxicities of treatments must be considered, especially in good prognosis patients. This study examined the outcome, risks of second cancers, and cardiac mortality with radiation therapy (RT) for early stage BC from recent years.
Materials and Methods
Analysis of Surveillance, Epidemiology, and End Results (SEER) database was conducted for women who had Stage T1aN0 BC as their first primary malignancy between 1990-1997 treated with partial or complete mastectomy ± external beam radiation. The overall survival (OS), breast cancer specific survival (BCSS), cardiac cause specific survival (CCS) and deaths from second cancers in the chest area were compared between the RT and no-RT groups.
Of the 6515 women identified, 2796 received RT and 3719 did not. The median age group (60-64 years) and follow up lengths (∼15 years) were similar. Compared to the RT group, the no-RT group was associated with lower 10-year OS (85.5% vs. 79.3%, p<0.0001), BCSS (97.3% vs. 96.4%, p=0.04), and CCS (97.0% vs. 93.8%, p<0.0001). In the RT group, left sided BC was not associated with higher cardiac mortality. There were no statistically significant incidences in mortality due to subsequent cancers. The most common second cancer mortality included 114 (2%) lung, 25 (0.4%) lymphoma, 19 (0.3%) leukemia, 3 (0.05%) soft tissue, and 2 (0.03%) esophagus.
This review of SEER data suggests that secondary malignancy in the chest area and cardiac mortality are rare after RT in the 1990’s for T1aN0 BC.
Clinical Breast Cancer 08/2014; · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An optic disc haemorrhage (DH) has been associated with subsequent structural glaucoma progression, but it is unknown if there is structural progression prior to a DH. We evaluated a cohort of patients to determine whether structural progression occurs before a DH, after a DH or is simply associated with a DH.
[Show abstract][Hide abstract] ABSTRACT: Purpose: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are considered the most aggressive cancers of the head and neck. The aim of the study was to evaluate and compare survival outcomes in PDTC and ATC in a large population-based cohort. Materials and Methods: Patients with PDTC and ATC diagnosed from 1973 to 2008 were obtained from Surveillance, Epidemiology, and End Results database. Kaplan-Meier survival analysis and log-rank analyses were performed to evaluate (1) The effect of histology on cause-specific survival (CSS) and (2) the influence of factors such as treatment, treatment sequence, race, sex, and age on CSS. Multivariate analysis was performed to assess the independent effect of these factors on CSS. Results: A total of 1352 patients with PDTC and ATC were identified. PDTC constituted 52.4% of patients versus 47.6% for ATC. Median CSS was similar in the two histology groups (P = 0.14). Both PDTC and ATC patients receiving radioisotopes showed a significantly better CSS compared to external beam radiation (P < 0.0001). PDTC and ATC Patients receiving radiation prior to surgery demonstrated a significantly lower CSS compared to patients receiving radiation postoperatively (P < 0.0001). Female gender and black/nonwhite race tended to improve CSS in PDTC and ATC patients (P = 0.29 and P = 0.03, for gender and race, respectively). However, multivariate analysis revealed only type of radiation treatment and age to be independently associated with CSS. Conclusion: This is the first large population-based study evaluating PDTC and ATC outcomes in patients who received radiation treatment. Radioisotope use and timing of radiotherapy (postoperative vs. preoperative) were associated with improved CSS in both histologies.
Journal of cancer research and therapeutics. 07/2014; 10(3):526-530.
[Show abstract][Hide abstract] ABSTRACT: Object Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole-brain radiotherapy (WBRT) remains the standard of care with a local control rate > 90%. However, WBRT is delivered over 10-15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 ((131)Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent (131)Cs brachytherapy at the resection for brain metastases. Methods After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded (131)Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity. Results The median follow-up was 19.3 months (range 12.89-29.57 months). The median age was 65 years (range 45-84 years). The median size of resected tumor was 2.7 cm (range 1.5-5.5 cm), and the median volume of resected tumor was 10.31 cm(3) (range 1.77-87.11 cm(3)). The median number of seeds used was 12 (range 4-35), with a median activity of 3.82 mCi per seed (range 3.31-4.83 mCi) and total activity of 46.91 mCi (range 15.31-130.70 mCi). Local FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI 63.2%-99.1%). One-year distant FFP was 48.4% (95% CI 26.3%-67.4%). Median OS was 9.9 months (95% CI 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI 29.1%-67.8%). Complications included CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis. Conclusions The use of postresection permanent (131)Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial.
Journal of Neurosurgery 05/2014; · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Object Incidental colloid cysts are frequently managed with surveillance imaging rather than surgical excision. This approach is born out of their purported indolent growth pattern and the surgical morbidity associated with microsurgical removal. The advent of endoscopic colloid cyst removal may offer renewed assessment of these patients who carry a risk of acute neurological deterioration. An evidence-based recommendation should weigh the risks of operative treatment. Thus far, there has been no concentrated assessment of cyst removal in patients with incidental colloid cysts. The major objective in this study was to define the risks associated with the endoscopic surgical removal of incidentally diagnosed colloid cysts Methods A retrospective review of the medical records was performed to search for patients evaluated for a colloid cyst between the years 1996 and 2012. Eighty-seven patients underwent colloid cyst resection, and 34 were managed with nonoperative surveillance imaging. Microsurgical resections, endoscopic resections of residual or recurrent colloid cysts, and cases with unknown preoperative symptomatic status were excluded from further analysis. Seventy-seven cases of primary endoscopic resections were identified. Twenty resections were performed in patients with an incidental diagnosis and 57 in symptomatic individuals. Presenting characteristics and surgical outcomes were compared between the incidental and symptomatic groups. Results The mean age at surgery was 39.65 years for the incidental and 43.31 years for the symptomatic group (p = 0.36). The median maximal cyst diameter was 9.7 mm (range 3-31 mm) for the incidental and 12 mm (range 5-34 mm) for the symptomatic group. The mean frontal and occipital horn ratio was 0.3928 for the incidental and 0.4445 for the symptomatic group (p = 0.002). Total resection was achieved in 90% of the incidental and 82.3% of the symptomatic cases (p = 0.49). The median hospital stay was 1 day for incidental and 2 days for symptomatic cases (p = 0.006). There were no deaths. There was one case of aseptic meningitis in the incidental group. In the symptomatic group there were 3 complications: one patient with subjective memory impairment, one with transient short-term memory deterioration, and another with a superficial wound infection treated with operative debridement. Two patients from the symptomatic group needed a CSF diversion procedure, and no shunting was needed in the incidental group. There were two recurrences in the symptomatic group (78 and 133 months postoperatively) and none in the incidental group (p = 1). Conclusions Age and cyst diameter were not correlated with the absence or presence of symptoms in patients with a colloid cyst of the third ventricle. Operative results were highly favorable in both groups and did not reveal a higher risk of morbidity in the patient presenting with an incidental lesion. The results support endoscopic resection as a legitimate therapeutic option for patients with incidental colloid cysts. Generalization of the operative results should be cautiously made, since this is a limited series and the results may depend on the degree of neuroendoscopic experience.
Journal of Neurosurgery 04/2014; · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT Radioimmunotherapy (RIT) is effective treatment for indolent non-Hodgkin's lymphomas (NHL), but response durations are usually limited, especially in aggressive NHL. We hypothesized that administration of bortezomib as a radiosensitizer with RIT would be tolerable and improve efficacy in NHL. This Phase 1 dose escalation study evaluated escalating doses of bortezomib combined with (131)I-tositumomab in patients with relapsed/refractory NHL. Twenty-five patients were treated. Treatment was well tolerated, with primarily hematologic toxicity. Maximum tolerated dose (MTD) was determined to be 0.9 mg/m(2) bortezomib, in combination with standard dose of 75 cGy (131)I-tositumomab. Sixteen patients responded (64%), including 44% complete responses (CR), with 82% CR in follicular lymphoma (FL) patients. At median follow up of 7 months, median progression-free survival was 7 months, and 7 of 11 FL patients remained in remission at a median of 22 months. In conclusion, bortezomib can be safely administered in combination with (131)I-tositumomab with promising response rates.
[Show abstract][Hide abstract] ABSTRACT: Background
Endoscopic endonasal (EE) transphenoidal surgery is as an important surgical approach to the treatment of sellar pathology, particularly for pituitary adenomas. Risk factors for the radiographic recurrence of pituitary adenomas resected using a purely endoscopic approach have not been established. This study investigates outcomes and identifies risk factors for recurrence following EE transphenoidal surgery for pituitary adenoma.
Clinical neurology and neurosurgery 04/2014; 119:75-79. · 1.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Object Surgical interventions for medically refractory epilepsy are effective in selected patients, but they are underutilized. There remains a lack of pooled data on complication rates and their changes over a period of multiple decades. The authors performed a systematic review and meta-analysis of reported complications from intracranial epilepsy surgery from 1980 to 2012. Methods A literature search was performed to find articles published between 1980 and 2012 that contained at least 2 patients. Patients were divided into 3 groups depending on the procedure they underwent: A) temporal lobectomy with or without amygdalohippocampectomy, B) extratemporal lobar or multilobar resections, or C) invasive electrode placement. Articles were divided into 2 time periods, 1980-1995 and 1996-2012. Results Sixty-one articles with a total of 5623 patients met the study's eligibility criteria. Based on the 2 time periods, neurological deficits decreased dramatically from 41.8% to 5.2% in Group A and from 30.2% to 19.5% in Group B. Persistent neurological deficits in these 2 groups decreased from 9.7% to 0.8% and from 9.0% to 3.2%, respectively. Wound infections/meningitis decreased from 2.5% to 1.1% in Group A and from 5.3% to 1.9% in Group B. Persistent neurological deficits were uncommon in Group C, although wound infections/meningitis and hemorrhage/hematoma increased over time from 2.3% to 4.3% and from 1.9% to 4.2%, respectively. These complication rates are additive in patients undergoing implantation followed by resection. Conclusions Complication rates have decreased dramatically over the last 30 years, particularly for temporal lobectomy, but they remain an unavoidable consequence of epilepsy surgery. Permanent neurological deficits are rare following epilepsy surgery compared with the long-term risks of intractable epilepsy.
Journal of Neurosurgery 02/2014; · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose To determine the effectiveness of bortezomib plus irinotecan and bortezomib alone in patients with advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma. We also sought to explore the effect of these therapeutics on tumor and normal gene expression in vivo. Methods Forty-one patients with advanced GEJ (89 %) or gastric (11 %) adenocarcinoma received bortezomib (1.3 mg/m(2) days 1, 4, 8, 11) plus irinotecan (125 mg/m(2) days 1, 8) every 21 days as first line therapy (N = 29), or bortezomib alone as second line therapy (N = 12). The trial was designed to detect a 40 % response rate for the combination, and 20 % response rate for bortezomib alone. Affymetrix HU133A gene chip arrays were used for gene expression studies. Results Objective response occurred in 3 of 29 patients (10 %, 95 % confidence intervals [CI] 2 %, 27 %) treated with bortezomib plus irinotecan, and in 1 of 12 patients (8 %, 95 % CI 0 %, 39 %) with bortezomib alone. Due to the limited number of responders, there were no significant correlations with response found in the gene expression profiles of 12 patients whose tumors were sampled before and 24 h after therapy with bortezomib alone (N = 2) or the combination (N = 10). Conclusions We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population.
Investigational New Drugs 02/2014; · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hematogenous metastasis accounts for the majority of cancer-related deaths, yet the mechanism remains unclear. Circulating tumor cells (CTCs) in blood may employ different pathways to cross blood endothelial barrier and establish a metastatic niche. Several studies provide evidence that prostate cancer (PCa) cell tethering and rolling on microvascular endothelium via E-selectin/E-selectin ligand interactions under shear flow theoretically promote extravasation and contribute to the development of metastases. However, it is unknown if CTCs from PCa patients interact with E-selectin expressed on endothelium, initiating a route for tumor metastases. Here we report that CTCs derived from PCa patients showed interactions with E-selectin and E-selectin expressing endothelial cells. To examine E-selectin-mediated interactions of PCa cell lines and CTCs derived from metastatic PCa patients, we used fluorescently-labeled anti-prostate specific membrane antigen (PSMA) monoclonal antibody J591-488 which is internalized following cell-surface binding. We employed a microscale flow device consisting of E-selectin-coated microtubes and human umbilical vein endothelial cells (HUVECs) on parallel-plate flow chamber simulating vascular endothelium. We observed that J591-488 did not significantly alter the rolling behavior in PCa cells at shear stresses below 3 dyn/cm(2). CTCs obtained from 31 PCa patient samples showed that CTCs tether and stably interact with E-selectin and E-selectin expressing HUVECs at physiological shear stress. Interestingly, samples collected during disease progression demonstrated significantly more CTC/E-selectin interactions than samples during times of therapeutic response (p=0.016). Analysis of the expression of sialyl Lewis X (sLe(x)) in patient samples showed that a small subset comprising 1.9-18.8% of CTCs possess high sLe(x) expression. Furthermore, E-selectin-mediated interactions between prostate CTCs and HUVECs were diminished in the presence of anti-E-selectin neutralizing antibody. CTC-Endothelial interactions provide a novel insight into potential adhesive mechanisms of prostate CTCs as a means to initiate metastasis.
PLoS ONE 12/2013; 8(12):e85143. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) cause significant visual impairment. The role of thrombophilia and cardiovascular testing is uncertain, and optimal treatment strategies have not been determined. We reviewed medical records of 39 patients with RVO and RAO (23 women and 16 men). Thrombophilia and cardiovascular evaluations were performed and outcomes were reviewed. In all, 24 (61.5%) patients had at least 1 thrombophilia. Elevated factor VIII levels were found in RVO (n = 5) but not in RAO. There are no other significant differences in thrombophilias in RVO compared to those in RAO. Most patients had hypertension(41.2% RAO and 55% RVO) and hyperlipidemia (35.5% RAO and 81.8% RVO). In all, 4 women were using oral contraceptives, 2 were pregnant or postpartum. Follow-up data was available for 28 patients (13 RAO, 15 RVO). Nineteen were treated with aspirin, four with warfarin, and one with low molecular weight heparin. Eight patients reported improvement in vision at time of follow-up (5 RAO, 3 RVO). Multiple risk factors are associated with RVO and RAO, and a complete assessment should include thrombophilia and cardiovascular studies.
Clinical and Applied Thrombosis/Hemostasis 12/2013; · 1.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prostate-specific membrane antigen (PSMA) has been found to be expressed in the tumor-associated neovasculature of multiple solid tumor types including breast cancers. However, thus far, the number of cases studied from some tumor types has been limited. In this study, we set out to assess PSMA expression in the tumor-associated vasculature associated with invasive breast carcinomas in a sizable cohort of patients. One hundred and six patients with AJCC stage 0-IV breast cancer were identified. Ninety-two of these patients had primary breast cancer [invasive breast carcinoma with or without co-existing ductal carcinoma in situ (DCIS) (74) or DCIS alone (18)]. In addition, 14 patients with breast cancer metastases to the brain were identified. Immunohistochemical staining for PSMA and CD31 was performed on parallel representative tumor sections in each case. Tumor-associated vascular endothelial cell PSMA immunoreactivity was semi-quantitatively assessed based on two parameters: overall percent of endothelial positivity and staining intensity. PSMA expression for tumor-associated vascular endothelial cells was scored 0 if there was no detectable PSMA expression, 1 if PSMA staining was detectable in 5-50%, and 2 if PSMA expression was positive in >50% of microvessels. CD 31 staining was concurrently reviewed to confirm the presence of vasculature in each case. Tumor-associated vasculature was PSMA-positive in 68/92 (74%) of primary breast cancers and in 14/14 (100%) of breast cancers metastatic to brain. PSMA was not detected in normal breast tissue or carcinoma cells. All but 2 cases (98%) showed absence of PSMA expression in normal breast tissue-associated vasculature. The 10-year overall survival was 88.7% (95% CI = 80.0%, 93.8%) in patients without brain metastases. When overall survival (OS) was stratified based on PSMA score group, patients with PSMA scores of 0, 1, and 2 had 10-year OS of 95.8%, 96.0%, and 79.7%, respectively (p = 0.12). When PSMA scores of 0 and 1 were compared with 2, there was a statistically significant difference in OS (96.0% vs 79.7%, respectively, p = 0.05). Patients with a PSMA score of 2 had a significantly higher median tumor size compared with patients in the lower PSMA score groups (p = 0.04). Patients with higher nuclear grade were more likely to have a PSMA score of 2 compared with patients with lower nuclear grade (p < 0.0001). Patients with a PSMA score of 2 had a significantly higher median Ki-67 proliferation index compared with patients in the lower PSMA score groups (p < 0.0001). Patients with estrogen receptor (ER)-negative tumors were more likely to have a PSMA score of 2 compared with patients with ER-positive tumors (p < 0.0001). Patients with progesterone receptor (PR)-negative tumors were more likely to have a PSMA score of 2 compared with patients with PR-positive tumors (p = 0.03). No significant association was observed between PSMA score group status and lymph node involvement (p = 0.95). Too little variability was present in Human epidermal growth factor receptor-2 (Her2/neu) amplified tumors to correlate with PSMA score group status. To date, this is the first detailed assessment of PSMA expression in the tumor-associated vasculature of primary and metastatic breast carcinomas. Further studies are needed to evaluate whether PSMA has diagnostic and/or potential therapeutic value.