Long term positional stability of the Argus II retinal prosthesis epiretinal implant.

BACKGROUND: The Argus II Retinal Prosthesis System (Second Sight Medical Products, Sylmar, California) is an epiretinal prosthesis that serves to provide useful vision to people who are affected by retinal degenerative diseases such as retinitis pigmentosa (RP). The purpose of this study was to analyze postoperative movement of the electrode array. METHODS: Five patients diagnosed with profound retinal dystrophy who have undergone implantation of retinal prosthesis at Stony Brook University Hospital. Fundoscopy was performed at postoperative month 1 (M1), month 3 (M3), month 6 (M6), month 12 (M12), and month 24 (M24) visits. Fundoscopy was extracted and analyzed via NIH ImageJ. Data analysis was completed using IBM SPSS. Various lengths and angles were measured each postoperative month using ImageJ. RESULTS: There was no significant change in distance between the optic disc and the surgical handle (length AB) over the two-year span (F = 0.196, p = 0.705). There was a significant change in distance of length AB over time between patients between M3 and M6 (p = 0.025). A repeated measures ANOVA revealed that there was statistically significant change of the optic disc-tack-surgical handle angle (𝛾) (M1 to M24) (F = 3.527, p = 0.030). There was no significant change in angle 𝜟 (the angle to the horizontal of the image), angle 𝜶 (tack-optic disc-surgical handle), and angle 𝜷 (optic-disc-surgical handle-tack). CONCLUSION: Our results demonstrate that there may be postoperative movement of the retinal prosthesis over time, as a statistically significant downward rotation is reported over the 2 years span. It is important, moving forward, to further study this movement and to take into consideration such movement when designing retinal implants. It is important to note that this study is limited by the small sample size, and therefore, the conclusions drawn are limited.

Rates and Outcomes of Breast Lesions of Uncertain Malignant Potential (B3) benchmarked against the National Breast Screening Pathology Audit; Improving Performance in a High Volume Screening Unit.

INTRODUCTION: Our breast screening unit was identified as high outlier for B3 lesions with a low positive predictive value (PPV) compared to the England average. This prompted a detailed internal audit and review of B3 lesions and their outcomes to identify causes and address any variation in practice. PATIENTS AND METHODS: The B3 rate was calculated in 4168 breast core biopsies from 2019, using the subsequent excision to determine the PPV. Atypical intraductal epithelial proliferation (AIDEP) cases were subject to microscopic review to reassess the presence of atypia against published criteria. The B3 rate was re-audited in 2021, and the results compared. RESULTS: Screening cases had a high B3 rate of 12.4% (30% above the national average), and a PPV of 7.7% (9.7% with atypia). AIDEP was identified as a possible cause of this outlier status. On review and by consensus, AIDEP was confirmed in only 66% of cases reported as such, 17% were downgraded, and 16% did not reach consensus, the latter highlighting the difficulty and subjectivity in diagnosis of these lesions. Repeat audit of B3 rates after this extended review revealed a reduction from 12.4% to 9.11%, which is more in line with national standards. CONCLUSION: Benchmarking against national reporting standards is critical for service improvement. Through a supportive environment, team working, rigorous internal review and adherence to guidelines, interobserver variation and outlier status in breast pathology screening outliers can both be addressed. This study can serve as a model to other outlier units to identify and tackle underlying causes.

Metastatic renal cell carcinoma initially presenting as a unilateral breast lump.

Breast metastasis from primary renal cell carcinoma is a rare entity and infrequently reported in the literature. We present a case of a 65-year-old lady who presented to breast clinic with a 4-month history of rapidly growing right sided breast lump. She previously had a left mastectomy for breast cancer and a hysterectomy for endometrial cancer. Radiological evaluation with mammography and ultrasound revealed a large heterogeneous right breast lump with prominent vascularity which was biopsied. Histopathological and immunohistochemical features were not supportive of a primary breast carcinoma and favored metastasis from a renal tumor. The patient was unfortunately admitted to hospital due to increasing confusion and neurological symptoms and underwent whole-body cross-sectional CT imaging which demonstrated a giant tumor originating from the right kidney with associated intrathoracic, breast and intracranial metastasis. She was diagnosed with eosinophilic variant metastatic renal cell carcinoma. This case highlights the importance of considering alternative diagnoses to primary breast carcinoma in the context of an initial presentation of a unilateral breast lump.

Gallbladder carcinosarcoma masquerading as a hepatic abscess.

Carcinosarcomas of the gallbladder are extremely rare tumors and infrequently reported in the literature. We demonstrate a case of a 64-year-old female who presented with a 2-month history of a right upper quadrant mass, intermittent fevers, and abdominal distension following recent travel to Ghana. A computed tomography (CT) scan of the abdomen and pelvis demonstrated a large hepatic lesion with co-existing gallbladder distension, suggestive of a hepatic abscess. The patient was initially managed with intravenous antibiotics but failed to respond to treatment. A subsequent magnetic resonance imaging (MRI) scan of the liver showed a locally invasive lobulated soft tissue lesion arising from the gallbladder fundus and extending into the liver parenchyma. The lesion was surgically excised with a central hepatectomy. Histopathologic analysis showed a carcinosarcoma of the gallbladder.

Effect of the electrode array-retina gap distance on visual function in patients with the Argus II retinal prosthesis.

BACKGROUND: Post-implantation visual outcomes in patients with the Argus II Retinal Prosthesis is dependent on a multitude of factors including the positioning of the electrode array on the retina. The purpose of this study is to determine whether the average electrode array-retina gap distance correlates with objective visual function outcomes and sensitivity detection thresholds in patients implanted with the Argus II Retinal Prosthesis. METHODS: Five patients with implantation of the Argus II Retinal Prosthesis were enrolled in this single-institution retrospective study. Patient demographics were collected from medical records. Visual function data (Square Localization [SL] and Direction of Motion [DOM]) and Optical Coherence Tomography (Cirrus HD-OCT) images were extracted retrospectively from the Argus II Retinal Prosthesis Post-Approval study. Visual function tests were performed with the device OFF and ON at each study visit. Electrode array-retina gap distances were measured at each of the array's 60 electrodes using the Cirrus HD-OCT software in both the nasotemporal and superoinferior planes. Data was obtained at baseline, and post-operative month 1, month 3, month 6, and year 1. Sensitivity detection thresholds were obtained at the initial programming visit and each reprogramming session. RESULTS: Three patients performed significantly better in SL visual function testing with the device ON. Patients that worsened in visual function testing with the device ON in both SL and DOM testing had a statistically significant decrease in performance. The electrode array-retina gap distance was found to effect performance in SL testing in a patient-dependent manner. No effect was found between the electrode-array gap distance and DOM testing or sensitivity detection threshold. CONCLUSION: Our results demonstrate that the electrode array-retina gap distance may affect visual function outcomes in SL testing in certain patients with the Argus II Retinal Prosthesis, and the direction and magnitude of this effect is likely patient-dependent. Furthermore, complete apposition between the electrode array and retina may not always be necessary to achieve optimal visual outcomes.

Index case of synovial metastasis in a patient with transitional cell carcinoma of the bladder.

Synovial metastasis is a rare presentation with only a few reported cases in the published literature. A majority of cases of malignant synovitis have a primary lung or colorectal origin. It carries a poor prognosis with an average survival of approximately 5 months from diagnosis. The treatment options are limited to palliative approaches, which highlight the aggressive nature of the presentation as well as the necessity for early recognition. We report an index case of synovial metastasis of the knee joint in a patient with progressive transitional cell carcinoma of the bladder and review the literature with respect to synovial metastasis.

PROPORTION OF PATIENTS WITH MACULAR HOLE SURGERY WHO WOULD HAVE BEEN FAVORABLE OCRIPLASMIN CANDIDATES: A Retrospective Analysis.

PURPOSE: To identify favorable ocriplasmin candidates from a cohort of idiopathic full thickness macular hole surgery patients. METHODS: The records of patients with full thickness macular hole who underwent pars plana vitrectomy surgery between 2011 and 2015 were reviewed. Clinical data collected included patient demographics, pre- and post-operative Snellen visual acuity, optical coherence tomography findings, and lens status. The authors defined "favorable" ocriplasmin candidates as patients with focal vitreomacular traction, no epiretinal membrane, and hole size ≤400 µm. The authors further categorized "optimal" candidates as age ≤65, phakic, no epiretinal membrane, with focal vitreomacular traction, and hole size ≤400 µm. RESULTS: The records of 238 patients were assessed; 30.7% were male while mean age was 68.6 ± 8.3 years. The mean logMAR acuity was 1.2 (Snellen 20/317) preoperatively and 0.90 (Snellen 20/159) postoperatively. Optical coherence tomography findings indicated that 46.5% of the macular holes studied were less than ≤400 µm in size, 14.8% had an epiretinal membrane, and 25.3% had vitreomacular traction. A total of 17.7% of study patients were found to be favorable candidates, whereas 3.8% were optimal ocriplasmin candidates. CONCLUSION: Only a minority of full thickness macular hole surgical candidates in this cohort would be considered favorable ocriplasmin candidates.

Optical coherence tomography-based positioning regimen for macular hole surgery.

PURPOSE: To evaluate an optical coherence tomography (OCT)-based positioning regimen for patients undergoing macular hole surgery. METHOD: We reviewed the medical records of all patients in our practice who underwent macular hole repair, instituting a modified OCT-based positioning regimen from November 1, 2011 through July 31, 2013. The regimen consisted of prone positioning at the conclusion of surgery with daily OCT imaging until the hole was confirmed closed at which point positioning was halted. Clinical data that were collected and recorded included visual acuities, stage of hole, size of hole, chronicity, preoperative and postoperative OCT imaging, and length of follow-up. RESULTS: We identified 33 patients (35 eyes) with a mean baseline visual acuity of 20/220, a mean hole size of 465 µm. The mean final (postoperative) visual acuity was 20/135 with a mean follow-up of 7.7 months. Six patients (17%) in our study were diagnosed with myopic degeneration. Thirteen patients (37%) were found to have chronic (≥12 months) holes, and 19 (54%) were found to have large holes (>400 µm). Overall, 28 eyes (80%) had persistent closure of macular holes with an OCT-based positioning regimen. In the absence of high risk factors, such as myopic degeneration, chronic or large holes, the closure rate was 92%. In the presence of 2 or 3 of these risk factors, the closure rate was 85% and 74%, respectively. CONCLUSION: The presence of 2 or 3 high risk factors, such as myopic degeneration, chronic holes (≥12 months), or large holes (>400 µm) can compromise outcomes resulting in reopening after apparent early closure. Based on the presence of these risk factors, a modified postoperative positioning regimen can be used to obtain complete and persistent closure.

Early initial clinical experience with intravitreal aflibercept for wet age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a degenerative process that leads to severe vision loss. Wet AMD is defined by choroidal neovascularisation, leading to the accumulation of subretinal fluid (SRF), macular oedema (ME), and pigment epithelium detachments (PED). Purpose To evaluate the initial clinical experience of conversion from bevacizumab or ranibizumab to aflibercept in wet AMD patients. METHODS: Records of 250 consecutive wet AMD patients were retrospectively reviewed. Of 250 patients, 29 were naive (with no previous treatment), and 221 were previously treated with bevacizumab (1/3) or ranibizumab (2/3). On average, converted patients received 14 injections every 6 weeks on a treat-and-extend regimen with Avastin or Lucentis before being converted to aflibercept every 7 weeks on average (no loading dose) for three doses. For the purposes of this study, we concentrated on the patients converted to aflibercept since the number of naive patients was too small to draw any conclusion from. Snellen (as logMar) visual acuities, and optical coherence tomography (OCT) were compared predrug and postdrug conversion. RESULTS: Converted patients did not show a significant difference in visual acuity or average OCT thickness from preconversion values; however, small improvements in ME (p=0.0001), SRF (p=0.0001), and PED (p=0.008) grading were noted on average after conversion to aflibercept. CONCLUSIONS: No significant difference in visual outcome or average OCT thickness was observed when switched from bevacizumab or ranibizumab q6 week to aflibercept 7-week dosing, on average. Mild anatomic improvements did occur in converted patients with regard to ME, SRF and PED improvement, on average, after conversion to aflibercept, and aflibercept was injected less frequently. No serious adverse reactions, including ocular infections or inflammation, as well as ocular and systemic effects were noted.

Pars plana vitrectomy in the management of patients diagnosed with endophthalmitis following intravitreal anti-vascular endothelial growth factor injection.

PURPOSE: To evaluate the possible benefit of pars plana vitrectomy in the treatment of patients with endophthalmitis following antivascular endothelial growth factor (VEGF) injection. METHOD: The authors retrospectively reviewed the medical records of all patients in their practice with a diagnosis of endophthalmitis from January 1, 2007, through December 31, 2011. Only those with a clinical presentation consistent with endophthalmitis after intravitreal anti-VEGF injection were included. Clinical data that were collected and recorded included visual acuities and the method of initial and subsequent treatment of endophthalmitis following anti-VEGF injection: tap and injection of intravitreal antibiotics (TAP) and tap and inject with subsequent pars plana vitrectomy (VIT). RESULTS: The authors identified 23 patients meeting criteria. Nineteen patients had received bevacizumab and four patients had received ranibizumab. The median time from last injection to presentation was 4 days (range, 1-18 days) with a median follow-up of 15 months (range, 5-48 months) after being diagnosed of endophthalmitis. Nine patients had positive cultures. The median baseline visual acuity (preendophthalmitis) was 20/70 (range, 20/25 to counting fingers at 2 ft) with a median presenting visual acuity of counting fingers at 1 ft (range, 20/50 to light perception vision). Overall, 90% (9/10) of the patients in TAP only group regained visual acuity within 1 line or better of baseline versus 46% (6 of 13) in the TAP and VIT group. Only one of the patients treated with TAP alone suffered more than one line of visual acuity loss. CONCLUSION: Patients diagnosed with endophthalmitis after anti-VEGF intravitreal injection who underwent TAP regained baseline visual acuity more often than those who underwent TAP and VIT. This study did not support a benefit for VIT in all patients, rather only in those cases who warranted it because of worsening clinical course. The study suggests that TAP is a viable primary intervention for endophthalmitis after anti-VEGF injection.

An evidence-based review of vascular endothelial growth factor inhibition in pediatric retinal diseases: part 2. Coats' disease, best disease, and uveitis with childhood neovascularization.

Vascular endothelial growth factor (VEGF) is an important factor in the pathogenesis of multiple retinal neovascular disorders. This report focuses on the quality and depth of new evidence for the use of VEGF inhibitors in selected pediatric ocular diseases, including Coats' disease, Best disease, and childhood uveitis. Because much of the literature comprises case reports and retrospective case series, the level of evidence supporting its use as a primary treatment option, or even as adjuvant therapy, is low. The standard of care is treatment of the underlying disorder to prevent neovascularization (retinal or subretinal), vitreous hemorrhage, or subsequent retinal detachment. However, these complications may not present until late in the disease course. It may then be useful to treat with these agents. Prospective studies are warranted to further elucidate the role of anti-VEGF therapy in these diseases.

An evidence-based meta-analysis of vascular endothelial growth factor inhibition in pediatric retinal diseases: part 1. Retinopathy of prematurity.

Recently there has been interest in the novel, off-label use of anti-vascular endothelial growth factor (anti-VEGF) agents for various stages of retinopathy of prematurity (ROP). The authors report on the quality and depth of new evidence published from 2009 to 2011 concerning the treatment of retinopathy of prematurity (ROP) with bevacizumab (Avastin; Genentech Inc., South San Francisco, CA) as either primary or adjunctive treatment for ROP. There is significant variability in the evidence, quality, and design of the studies available in the literature. There has been a trend in the scientific literature of the past 2 years toward larger, multi-center, randomized studies investigating the role of bevacizumab in the treatment of ROP. More recent evidence suggests that monotherapy with intravitreal bevacizumab may be a viable first-line treatment for select cases of zone I ROP and possibly for posterior zone II disease. Adjunctive treatment with bevacizumab may enhance outcomes in patients treated with laser photocoagulation or pars plana vitrectomy. However, there are significant concerns regarding its long-term safety profile. Further prospective studies are warranted to more fully determine the role of anti-VEGF therapy in this disease.

Immune reconstitution uveitis complicated by vitreoretinal traction and formation of a retinal tear.

The authors report a case of immune reconstitution uveitis induced by cytomegalovirus retinitis with subsequent development of vitreoretinal traction and a resultant retinal tear.

Macular epiretinal membrane peeling treatment outcomes in young children.

PURPOSE: The purpose of this study was to describe macular epiretinal membrane (ERM) peeling treatment outcomes in young children. METHODS: The medical records of all vitrectomies from 1998 through 2010 were retrospectively reviewed. Patients who were selected were 16 years or younger and had primarily macular or posterior pole disease secondary to an ERM. Patients with retinopathy of prematurity, Coats disease, Norrie disease, and incontinentia pigmenti were excluded. Fourteen patients underwent vitrectomy with ERM peeling, and their preoperative and postoperative visual acuities were compared. RESULTS: The mean age at surgery was 8 years, with an average follow-up of 4.2 years (range, 6 months to 11 years). The average presenting visual acuity was 20/258. Average postoperative visual acuity was 20/100, with improvement in 12 patients (86%) and no change of visual acuity in 2 patients (14%). CONCLUSION: Pediatric ERMs respond well to vitrectomy and membrane peel with a low likelihood of recurrence. Other associated pathology, such as familial exudative retinopathy and combined hamartomas of the retina and retinal pigment epithelium, was associated with complications, such as delayed-onset rhegmatogenous retinal detachment from peripheral traction and recurrence of ERM in 7% of patients.

Transmural eosinophilic gastritis with gastric outlet obstruction: case report and review of the literature.

Eosinophil-associated gastrointestinal disorders (EGIDs) are uncommon conditions whose aetiologies are unclear, but which are characterised by eosinophilic infiltration and inflammation of the gastrointestinal tract in the absence of other causes of eosinophilia. We report the case of a 65-year-old woman with eosinophilic gastritis who underwent a Polya gastrectomy for a suspected gastric tumour with gastric outflow obstruction. Subsequent histological examination showed a non-malignant transmural eosinophilic infiltration of the stomach wall, a rare pathological entity. We present a review of the literature and discuss the management of such cases.

Differential effects of toremifene on doxorubicin, vinblastine and Tc-99m-sestamibi in P-glycoprotein-expressing breast and head and neck cancer cell lines.

The effect of toremifene on P-glycoprotein-mediated multidrug resistance (MDR) in breast and head and neck cancer cell lines was measured in vitro and in vivo. Pgp expression was low and high, respectively, in drug-sensitive (MCF7-S, KB) and drug-resistant (MCF7-R, MCF7-R1, KBV1) cell lines. Toremifene (7.5 microM) significantly enhanced cytoplasmic and nuclear accumulation of doxorubicin in drug-resistant cells. Toremifene (10 microM) increased the in vitro cytotoxicity of doxorubicin in drug-resistant breast cancer cells (13-fold and 21-fold for MCF7-R and MCF7-R1, respectively) without affecting the sensitivity of MCF7-S cells. Similarly, toremifene (10 microM) caused a 12-fold increase in the sensitivity of KBV1 cells to vinblastine. In contrast, toremifene (5 microM) reduced the net uptake of the radiolabelled Pgp substrate, Tc-99m-sestamibi, in the Pgp-overexpressing cell lines by factors of 0.32 and 0.42 for MCF7-R1 and KBV1 cells, respectively (p < 0.01), and, to a lesser extent, by corresponding factors of 0.89 and 0.86 in the drug-sensitive cell lines (p < 0.05 and p > 0.05, respectively). In nude mice bearing both KB and KBV1 xenograft tumours, significantly higher tumour levels of Tc-99m-sestamibi were recorded in KB tumours compared with KBV1 tumours. After 3 days of treatment with intraperitoneal toremifene (25 mg/kg), tumour levels of Tc-99m-sestamibi were reduced in KB and KBV1 tumours but only statistically significantly for KB tumours. Toremifene is a potent MDR modulating agent with respect to chemotherapeutic agents but has the opposite effect with respect to Tc-99m-sestamibi. This finding is of importance in view of the widespread use of Tc-99m-sestamibi as an imaging surrogate for a chemotherapeutic agent.

Ligand activation of the androgen receptor downregulates E-cadherin-mediated cell adhesion and promotes apoptosis of prostatic cancer cells.

Androgen independence is the major cause of endocrine therapy failure in advanced prostate cancer (PC). To examine the effects of human androgen receptor (AR) expression on growth of human PC cells, transfection of full-length AR cDNA in an androgen-insensitive human prostatic adenocarcinoma cell line (DU145) was performed. Transcriptional activity of AR was confirmed by the MMTV luciferase assay and AR expression was assessed by reverse transcriptase polymerase chain reaction, Western blotting, and immunocytochemistry. Two stable transfectant cell lines expressing functional AR were established and passaged over 60 times. Under standard culture conditions, AR expression in transfected cells was predominantly cytoplasmic. Exposure to dihydrotestosterone (DHT; 60 pM-10 nM) resulted in a rapid (maximal at 30 minutes) translocation of AR to the nucleus. Treatment with DHT (5 nM) caused a significant reduction in cell-cell adhesion and aggregation accompanied by a decrease in E-cadherin expression. This was associated with up to 40% inhibition of proliferation and approximately two-fold increase in apoptosis. These results suggest that gene transfer-mediated AR expression in DU145 cells confers sensitivity to DHT, modulates cell-cell adhesion through E-cadherin, and suppresses cell growth by inhibiting proliferation and promoting apoptosis. This provides amodelfor studies ofAR-regulated cell signalling and identification of novel androgen-regulated genes in PC.

99mTc-sestamibi imaging in the assessment of toremifene as a modulator of multidrug resistance in patients with breast cancer.

UNLABELLED: Multidrug resistance (MDR) due to expression of a membrane-associated permeability glycoprotein (P-glycoprotein [Pgp]) prevents successful cytotoxic chemotherapy for breast cancer. Identification of MDR would facilitate selection of chemotherapy regimens and MDR modulators. This study aimed to evaluate (99m)Tc-sestamibi imaging for predicting overexpression of Pgp in primary breast cancer and to measure the efficacy of toremifene, the MDR modulator, in vivo. METHODS: Twenty patients with untreated breast cancer had (99m)Tc-sestamibi imaging 20 and 120 min after tracer injection before and after a 3-d course of toremifene (780 mg/d). Tumor samples were obtained during surgery for correlation of imaging and Pgp immunohistochemistry. RESULTS: Sixteen of 20 tumors were visualized with sestamibi. Before toremifene, there was a significant inverse correlation (Spearman rank correlation coefficient [R(S)]) between staining intensity, based on the anti-Pgp monoclonal antibodies C494 and C219, and the tumor-to-background ratio (T/B) at 120 min (R(S) = -0.85; P < 0.001 and R(S) = -0.71; P < 0.001, respectively). However, the correlation between the T/B and immunohistochemistry at 20 min was significant only for C494 (R(S) = -0.57; P < 0.01). Similarly, before toremifene, there was an inverse correlation between staining intensity and the change in the T/B between 20 and 120 min (R(S) = -0.77; P < 0.001 and -0.75; P < 0.001 for C494 and C219). After toremifene, an inverse correlation between staining intensity and the T/B was seen only at 120 min and only with C494 (R(S) = -0.68; P < 0.01). However, the change in the T/B between 20 and 120 min correlated significantly with staining intensity for C494 and C219 (R(S) = -0.68; P < 0.01 and -0.7; P < 0.01 for C494 and C219, respectively). Toremifene did not significantly alter the overall T/B at either 20 or 120 min when data were compared before and after toremifene. Nevertheless, at 120 min, 8 of 8 tumors with low Pgp expression showed reduced uptake after toremifene, whereas 5 of 6 tumors with strong expression showed increased uptake (P < 0.003). Moreover, there was a significant correlation between the change in the T/B and staining intensity with C494 (R(S) = 0.59; P < 0.05) and C219 (R(S) = 0.56; P < 0.05) at 120 min but not at 20 min. CONCLUSION: (99m)Tc-Sestamibi accumulation in breast cancer correlates with Pgp expression. Toremifene has a dual effect on this accumulation, increasing it through an inhibitory effect on Pgp while at the same time reducing it by a direct competition with sestamibi. The latter implies that in response to Pgp modulation the efflux of various agents may be affected differently.

Androgen-dependent regulation of human MUC1 mucin expression.

MUC1 mucin is transcriptionally regulated by estrogen, progesterone, and glucocorticoids. Our objective was to determine whether androgen receptor (AR) activation regulates expression of MUC1. The following breast and prostatic cell lines were phenotyped and grouped according to AR and MUC1 protein expression: 1) AR+MUC1 + [DAR17+19 (AR transfectants of DU-145), ZR-75-1, MDA-MB-453, and T47D]; 2) AR-MUC1 + [DZeo1 (AR-vector control), DU-145, BT20, MDA-MB-231, and MCF7]; 3) AR+MUC1 - (LNCaP and LNCaP-r). Cell proliferation was determined using the MTT assay in the presence of synthetic androgen R1881, 0.1 microM to 1 microM. Cell surface MUC1 expression was determined by flow cytometry in the presence or absence of oestradiol, medroxy progesterone acetate or R1881, with and without 4 hydroxy-flutamide (4-OH), a nonsteroidal AR antagonist. The functional significance of MUC1 expression was investigated with a cell-cell aggregation assay. Only AR+MUC1 + cell lines showed a significant increase in MUC1 expression with AR activation (P (range) =.01 to .0001), reversed in the presence of 4-OHF. Cell proliferation was unaffected. Increased expression of MUC1 was associated with a significant (P (range) = .002 to .001) reduction in cell-cell adhesion. To our knowledge, this is the first description of androgen-dependent regulation of MUC1 mucin. This is also functionally associated with decreased cell-cell adhesion, a recognised feature of progressive malignancy. These findings have important implications for physiological and pathological processes.

MUC1 mucin and trefoil factor 1 protein expression in renal cell carcinoma: correlation with prognosis.

This study examines the coexpression of MUC1 mucin and trefoil factor 1 (TFF1) and their relationship to progression of renal cell carcinoma (RCC). Immunohistochemistry was performed on tumor and adjacent normal tissue from clear-cell RCC (n = 60) and tissues from normal controls (n = 5) using a set of well-characterized monoclonal antibodies recognizing different epitopes of MUC1 and TFF1. Results of immunohistochemistry were compared with clinical parameters, including tumor grade, tumor size, presence of metastasis, and progression-free survival of patients after surgery. In normal tissue, MUC1 and TFF1 were absent from the normal proximal tubular epithelium but were identified in distal and collecting tubular epithelium. In RCC, increased MUC1 expression positively correlated to tumor progression. MUC1 recognized by HMFG1 was associated with large tumor size (P < .05), distant metastasis (P < .05), and invasion of large veins (P < .05). Expression of the under-glycosylated form of MUC1 recognized by SM3 was found to correlate to time to progression (recurrence, metastasis, or death of patient; P < .001). Expression of TFF1 did not significantly correlate with any prognostic parameters. However, there was a significant correlation (P < .01) between TFF1 and MUC1 expression (HMFG2 epitope) in RCCs. These results are consistent with the following conclusions: (1) MUC1 may be an independent prognostic marker in RCC; (2) TFF1 is frequently coexpressed with MUC1 and may act synergistically; and (3) RCC may originate from distal tubular epithelium.