Dr. Lui studied physics as an undergraduate at Harvard before attending medical school at Johns Hopkins. She completed a general surgery residency at the University of California San Francisco, which included two years of research in the UCSF Thoracic Oncology Laboratory and completion of a Master in Advanced Studies in clinical research. Dr. Lui went on to hold a fellowship in Thoracic Surgery at Massachusetts General Hospital, during which she participated in visiting rotations at Memorial Sloan Kettering and the Mayo Clinic.
Dr. Lui specializes in minimally invasive thoracic surgery, including robotic thoracic surgery. Her clinical focus extends to all aspects of general thoracic surgical diseases, including lung and esophageal cancer and airway diseases such as tracheomalacia. Her research focus is clinical and translational, including intraoperative fluorescence imaging. She is happy to be back in California and enjoys the warm weather, good food, and beautiful outdoors.
- Lung cancer
- Esophageal cancer
- Mediastinal tumors
- Airway tumors
- Minimally invasive surgery
- Robotic surgery
- Thoracic Surgery (Cardiothoracic Vascular Surgery)
Assistant Professor - Med Center Line, Cardiothoracic Surgery
Unit-Based Medical Director, D2/G2S, Stanford Hospital (2019 - Present)
Honors & Awards
Carolyn E. Reed Traveling Fellowship Award, Thoracic Surgery Foundation (2018)
Donald B. Doty Educational Award, Western Thoracic Surgical Association (2019)
Board Certification: Thoracic Surgery (Cardiothoracic Vascular Surgery), American Board of Thoracic Surgery (2019)
BA, Harvard University, Physics (2002)
MD, Johns Hopkins School of Medicine, Medicine (2007)
MAS, University of California San Francisco, Clinical research (2012)
Residency, University of California San Francisco, General surgery (2014)
Fellowship, Massachusetts General Hospital, Thoracic surgery (2016)
Panitumumab-IRDye800 in Detecting Cancer in Participants With Lung Cancer During Surgery
This phase I/II trial studies the best dose and timing of panitumumab-IRDye800 in detecting cancer in participants with lung cancer during the surgery. Panitumumab-IRDye800 is a combination of the antibody drug panitumumab and IRDye800CW, an investigational dye that can be seen using a special camera. Panitumumab-IRDye800 may attach to tumor cells and make them more visible during surgery in patients with lung cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Nicholas Oberhelman, 650-724-3866.
The Oldest Old: A National Analysis of Outcomes for Patients 90 Years or Older With Lung Cancer.
The Annals of thoracic surgery
BACKGROUND: Most clinicians will encounter patients 90 years or older with non-small cell lung cancer (NSCLC), but evidence that informs treatment decisions for this extremely elderly population is lacking. This study evaluated outcomes associated with treatment strategies for this nonagenarian population.METHODS: Treatment and overall survival for patients 90 years and older with NSCLC in the National Cancer Data Base (2004-2014) were evaluated using logistic regression, the Kaplan-Meier method, and multivariable Cox proportional hazard models.RESULTS: The majority (n = 4152, 57.6%) of the 7205 patients 90 years or older with stage I-IV NSCLC did not receive any therapy. For the entire cohort, receiving treatment was associated with significantly better survival when compared with no therapy (5-year survival, 9.3% [95% confidence interval [CI], 8.0%-10.7%] vs 1.7% [95% CI, 1.2%-2.2%]; multivariable adjusted hazard ratio, 0.53; P < .001). Stage I patients had the most pronounced survival benefit with treatment (median survival, 27.4 months vs 10.0 months with no treatment; P < .001). Among this subset of patients with stage I disease (n= 1430), only 12.7% (n= 182) had surgery and 33% (n= 471) had no therapy. In these stage I patients surgery was associated with significantly better 5-year survival (33.7% [95% CI, 25.4%-42.1%]) than nonoperative therapy (17.1% [95% CI, 13.7%-20.8%]) and no therapy (6.2% [95% CI, 3.8%-9.4%]).CONCLUSIONS: Therapy for nonagenarians with NSCLC is associated with a significant survival benefit but is not used in most patients. Treatment should not be withheld for these "oldest old" patients based on their age alone but should be considered based on stage and patient preferences in a multidisciplinary setting.
View details for DOI 10.1016/j.athoracsur.2019.09.027
View details for PubMedID 31757356
National Evaluation of Short-Term and Intermediate-Term Readmission after Esophagectomy
ELSEVIER SCIENCE INC. 2019: S279–S280
View details for Web of Science ID 000492740900545
Management of Benign Esophageal Perforation in the National Inpatient Sample
ELSEVIER SCIENCE INC. 2019: E209
View details for Web of Science ID 000492749600500
Single-Lumen Endotracheal Tube and Bronchial Blocker for Airway Management During Tracheobronchoplasty for Tracheobronchomalacia: A Case Report.
We present a case of a 69-year-old man who underwent tracheobronchoplasty for tracheobronchomalacia using a single-lumen endotracheal tube and a Y-shaped bronchial blocker for airway management. Tracheobronchoplasty is performed by sewing mesh to plicate the posterior, membranous wall of the distal trachea and main bronchi through a right posterolateral thoracotomy. The goals of airway management include continuous left-lung ventilation and lung protection from aspiration. Ideally, only conventional airway management tools are used. This case demonstrates that a single-lumen endotracheal tube with a bronchial blocker can be a straightforward strategy for airway management during tracheobronchoplasty.
View details for DOI 10.1213/XAA.0000000000001076
View details for PubMedID 31385817
Unconscious Bias: Addressing the Hidden Impact on Surgical Education.
Thoracic surgery clinics
2019; 29 (3): 259–67
Unconscious (or implicit) biases are learned stereotypes that are automatic, unintentional, deeply engrained, universal, and able to influence behavior. Several studies have documented the effects of provider biases on patient care and outcomes. This article provides a framework for exploring the implications for unconscious bias in surgical education and highlights best practices toward minimizing its impact. Presented is the background related to some of the more common unconscious biases and effects on medical students, resident trainees, and academic faculty. Finally, targeted strategies are highlighted for individuals and institutions for identification of biases and the means to address them.
View details for DOI 10.1016/j.thorsurg.2019.03.004
View details for PubMedID 31235294
A National Analysis of Short-term Outcomes and Long-term Survival Following Thoracoscopic Versus Open Lobectomy for Clinical Stage II Non-Small-Cell Lung Cancer.
Annals of surgery
MINI: In this national analysis, thoracoscopic lobectomy was associated with shorter hospital stay and no significant difference in long-term survival when compared to open lobectomy for cT1-2N1M0 non-small-cell lung cancer (NSCLC). These results suggest that thoracoscopic techniques are feasible in the treatment of stage II (cN1) NSCLC.OBJECTIVE: To compare outcomes after open versus thoracoscopic (VATS) lobectomy for clinical stage II (cN1) non-small-cell lung cancer (NSCLC).BACKGROUND: There have been no published studies evaluating the impact of a VATS approach to lobectomy for N1 NSCLC on short-term outcomes and survival.METHODS: Outcomes of patients with clinical T1-2, N1, M0 NSCLC who underwent lobectomy without induction therapy in the National Cancer Data Base (2010-2012) were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis.RESULTS: Median follow-up of 1559 lobectomies (1204 open and 355 VATS) was 43.2 months. The VATS approach was associated with a shorter median hospitalization (5 vs 6 d, P < 0.001) than the open approach. There were no significant differences between the VATS and open approach with regard to nodal upstaging (12.0% vs 10.5%, P = 0.41), 30-day mortality (2.3% vs 3.1%, P = 0.31), and overall survival (5-yr survival: 48.6% vs 48.7%, P = 0.76; multivariable-adjusted HR for VATS approach: 1.08, 95% CI: 0.90-1.30, P = 0.39). A propensity score-matched analysis of 334 open and 334 VATS patients who were well matched by 14 common prognostic covariates, including tumor size, and comorbidities, continued to show no significant differences in nodal upstaging, 30-day mortality, and 5-year survival between the VATS and open groups.CONCLUSION: In this national analysis, VATS lobectomy was used in the minority of N1 NSCLC cases but was associated with shorter hospitalization and similar nodal upstaging rates, 30-day mortality, and long-term survival when compared to open lobectomy. These findings suggest thoracoscopic techniques are feasible for the treatment of stage II (cN1) NSCLC.
View details for PubMedID 30946089
Examination of Factors Associated With Lymph Node Metastases in Lung Carcinoids
LIPPINCOTT WILLIAMS & WILKINS. 2019: 447
View details for Web of Science ID 000462541800096
The influence of hormone replacement therapy on lung cancer incidence and mortality.
The Journal of thoracic and cardiovascular surgery
Data regarding the effects of hormone replacement therapy (HRT) on non-small cell lung cancer (NSCLC) are mixed. We hypothesized HRT would have a protective benefit with reduced NSCLC incidence among women in a large, prospective cohort.We used data from the multicenter randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2001). Participants were women aged 50 to 74 years followed prospectively for up to 13 years for cancer screening. The influence of HRT on the primary outcome of NSCLC incidence and secondary outcomes of all-cause and disease-specific mortality were assessed with Kaplan-Meier analysis and Cox proportional hazard models adjusting for covariates.In the overall cohort of 75,587 women, 1147 women developed NSCLC after a median follow-up of 11.5 years. HRT use was characterized as 49.4% current users, 17.0% former users, and 33.6% never users. Increased age, smoking, comorbidities, and family history were associated with increased risk of NSCLC. On multivariable analysis, current HRT use was associated with reduced risk of NSCLC compared with never users (hazard ratio, 0.80; 95% confidence interval, 0.70-0.93; P = .009). HRT or oral contraception use was not associated with significant differences in all-cause mortality or disease-specific mortality.These data represent among the largest prospective cohorts suggesting HRT use may have a protective effect on the development of NSCLC among women; the physiological basis of this effect merits further study; however, the results may influence discussion surrounding HRT use in women.
View details for DOI 10.1016/j.jtcvs.2019.10.070
View details for PubMedID 31866083
- Commentary: Pleomorphic carcinoma: An aggressive type of non-small cell lung cancer that should be treated like the others. The Journal of thoracic and cardiovascular surgery 2019
Cut it out! Thoracic Surgeon's Approach to Pulmonary Mucormycosis and the Role of Surgical Resection in Survival.
Mucormycosis portends a poor prognosis with mortality rates ranging from 50-70% in pulmonary mucormycosis (PM) and up to 95% in disseminated disease. However, detailed outcomes data have been lacking. It remains unknown how to identify patients who would benefit from surgical resection.We present our experience with patients undergoing surgical resection for PM, including an analysis of factors affecting postoperative survival. We also describe a thoracic surgeon's approach through illustrative cases.We conducted a single-center retrospective study of all adult patients with PM who received antifungal therapy and underwent surgical resection or who received antifungal therapy alone at Stanford between January 2004 and June 2018.Twelve patients received antifungal therapy and underwent surgical resection and 13 patients received antifungal therapy alone. From infection onset to death (or right-censoring if still alive), patients who underwent surgical resection had a median survival of 406 days (mean, 561.3; range, 22-2,510), and patients who received antifungal therapy alone had a median survival of 28 days (mean, 66.7; range, 8-447). In patients who underwent surgical resection, median postoperative survival time was 154 days (range, 11-2,495), in-hospital mortality was 16.7%, and 1-year mortality was 50.0%. Age, primary disease, ASA status, extrapulmonary dissemination, laterality, multilobar involvement, number of lesions, largest lesion size, platelet count, surgical approach, type of resection, or extent of resection were not significantly associated with postoperative survival.Surgical resection significantly increases survival and should be strongly considered for selected patients with PM. This article is protected by copyright. All rights reserved.
View details for DOI 10.1111/myc.12954
View details for PubMedID 31173415
- Commentary: Should lung cancer screening guidelines go up in smoke? The Journal of thoracic and cardiovascular surgery 2019
Surgical Management for Aortoesophageal Fistula After Endovascular Aortic Repair.
The Annals of thoracic surgery
This case demonstrates successful surgical management of a 6 cm-long aortoesophageal fistula from an infected stent graft. A 69-year-old woman with a penetrating descending thoracic aortic ulcer underwent endovascular aortic repair. Two weeks later, she presented with nausea and melena, and was found to have an infected stent graft on imaging. She underwent a two-stage procedure encompassing aortic arch debranching and extra-anatomic aortic bypass in stage one, and stent graft resection, primary esophageal repair, intercostal and omental flap and jejunostomy tube placement in stage two. She was discharged one month later and is doing well 1.5 years after the operation.
View details for DOI 10.1016/j.athoracsur.2019.08.076
View details for PubMedID 31586613
- Neoadjuvant chemotherapy versus chemoradiotherapy for esophageal cancer: a tradeoff between dysphagia and pathologic response VIDEO-ASSISTED THORACIC SURGERY 2018; 3
Yellow nail syndrome with chylothorax after coronary artery bypass grafting.
Journal of cardiothoracic surgery
2018; 13 (1): 93
BACKGROUND: Yellow nail syndrome is a rare condition considered secondary to functional anomalies of lymphatic drainage. Yellow nail syndrome is diagnosed through the triad of intrathoracic findings (30% being pleural effusions), nail discoloration, and lymphedema, with any two features sufficient for diagnosis. We report the second case of post-operative yellow nail syndrome.CASE PRESENTATION: After coronary artery bypass grafting, our patient presented with chylothorax on post-operative day 13 and yellow toenail discoloration on post-operative day 28, diagnosing yellow nail syndrome. Initial conservative management with pigtail catheter drainage and low-fat diet with medium-chain triglycerides reduced chylous drainage from 350mL/day on post-operative day 14 to <100mL/day on post-operative day 17. However, by post-operative day 18, drainage returned to 350mL/day that persisted despite attempts to readjust the catheter position, replacement of catheter with chest tube, and transition to total parenteral nutrition and octreotide while nil per os. Lymphangiogram on post-operative day 32 did not identify the thoracic duct or cisterna chyli, precluding embolization. Talc and doxycycline pleurodeses performed on post-operative days 33 and 38, respectively, resolved his chylothorax and nail discoloration.CONCLUSIONS: Both yellow nail syndrome and chylothorax as a complication of coronary artery bypass grafting are rare entities. The proposed mechanism of post-operative chylothorax is iatrogenic injury to thoracic duct or collateral lymphatic vessels. Diagnosing yellow nail syndrome in patients with post-operative chylothorax (through co-existing yellow nail discoloration and/or lymphedema) may suggest predisposition to impaired lymphatic drainage, portending a difficult recovery and potentially indicating need for surgical management.
View details for PubMedID 30201014
Induction therapy for locally advanced distal esophageal adenocarcinoma: Is radiation Always necessary?
The Journal of thoracic and cardiovascular surgery
OBJECTIVE: To compare outcomes between induction chemotherapy alone (ICA) and induction chemoradiation (ICR) in patients with locally advanced distal esophageal adenocarcinoma.METHODS: Patients in the National Cancer Database treated with ICA or ICR followed by esophagectomy between 2006 and 2012 for cT1-3N1M0 or T3N0M0 adenocarcinoma of the distal esophagus were compared using logistic regression, Kaplan-Meier analysis, and Cox proportional hazards methods.RESULTS: The study group included 4763 patients, of whom 4323 patients (90.8%) received ICR and 440 patients (9.2%) received ICA. There were no differences in age, sex, race, Charlson Comorbidity Index, treatment facility type, clinical T or N status between the 2 groups. Tumor size ≥5cm (odds ratio, 1.46; P=.006) was the only factor that predicted ICR use. Higher rates of T downstaging (39.7% vs 33.4%; P=.012), N downstaging (32.0% vs 23.4%; P<.001), and complete pathologic response (13.1% vs 5.9%; P<.001) occurred in ICR patients. Positive margins were seen more often in ICA patients (9.6% vs 5.5%; P=.001), but there was no difference in 5-year survival (ICR 35.9% vs ICA 37.2%; P=.33), and ICR was not associated with survival in multivariable analysis (hazard ratio=1.04; P=.61).CONCLUSIONS: ICR for locally advanced distal esophageal adenocarcinoma is associated with a better local treatment effect, but not improved survival compared with ICA, which suggests that radiation can be used selectively in this clinical situation.
View details for PubMedID 29530567
Ground-glass opacity heralding invasive lung adenocarcinoma with prodromal dermatomyositis: a case report
JOURNAL OF CARDIOTHORACIC SURGERY
2018; 13: 20
Dermatomyositis, an inflammatory myopathy with cutaneous involvement, is associated with malignancy and often manifests paraneoplastically. While co-occurrence with small cell carcinoma is well attested, primary lung adenocarcinoma, which may present as focal ground-glass opacification on computed tomography of the thorax, is less frequently coincident.We report the case of a 72-year-old female patient with dermatomyositis - treated with a combination of prednisone, methotrexate, and intravenous immunoglobulin - and an indolent, subsolid, non-hypermetabolic pulmonary lesion, which was determined to be invasive primary lung adenocarcinoma. Supporting a paraneoplastic basis, immunosuppressive therapy was discontinued following tumor excision without relapse of signs or symptoms of dermatomyositis.While dermatomyositis prodromal to lung adenocarcinoma is not without precedent, association with an indolent, subsolid lesion has, to the best of our knowledge, not been reported. The case described herein illustrates the importance of maintaining a high index of suspicion for malignancy in the setting of dermatomyositis.
View details for PubMedID 29415746
A Novel and Successful Repair of a Left Atriogastric Fistula After Esophagectomy.
The Annals of thoracic surgery
2017; 104 (2): e157–e159
Atriogastric fistulas remain a rare adverse event in patients who undergo esophagectomy with gastric pullthrough. The presentation of an atriogastric fistula ranges from self-limited gastrointestinal bleeding to life-threatening hemorrhage, end-organ dysfunction from septic emboli, or both. These fistulas are associated with significant mortality. Previous reports describe successful repairs of gastrocardiac fistulas with the use of cardiopulmonary bypass. This report describes a patient with a significant burden of cerebral embolic disease, which therefore required a unique approach to fistula repair.
View details for DOI 10.1016/j.athoracsur.2017.02.079
View details for PubMedID 28734441
SULF2 Expression Is a Potential Diagnostic and Prognostic Marker in Lung Cancer
2016; 11 (2)
Lung cancer is one of the most deadly cancers; median survival from diagnosis is less than one year in those with advanced disease. Novel lung cancer biomarkers are desperately needed. In this study, we evaluated SULF2 expression by immunohistochemistry and its association with overall survival in a cohort of patients with non-small cell lung cancer (NSCLC). We also looked for the presence of SULF2 protein in plasma to evaluate its potential as an early detection biomarker for NSCLC.We identified patients who underwent surgical resection for pulmonary adenocarcinoma or squamous cell carcinoma at our institution. A section from each paraffin-embedded specimen was stained with a SULF2 antibody. A pathologist determined the percentage and intensity of tumor cell staining. Survival analysis was performed using a multivariate Cox proportional hazards model. Using a novel SULF2 ELISA assay, we analyzed plasma levels of SULF2 in a small cohort of healthy donors and patients with early stage NSCLC.SULF2 staining was present in 82% of the lung cancer samples. Squamous cell carcinomas had a higher mean percentage of staining than adenocarcinomas (100% vs. 60%; p<0.0005). After adjusting for age, sex, race, histologic type, stage, and neoadjuvant therapy, there was a non-significant (31%; p = 0.65) increase in the risk of death for patients with adenocarcinoma with SULF2 staining in tumor cells. In contrast, there was a significant decrease in the risk of death (89%; p = 0.02) for patients with squamous cell carcinoma with SULF2 staining in tumor cells. SULF2 protein was present in plasma of patients with early stage NSCLC, and soluble SULF2 levels increased with age. Finally, plasma SULF2 levels were significantly elevated in early stage NSCLC patients, compared to healthy controls.Tumor expression of SULF2 may affect prognosis in NSCLC, while blood SULF2 levels may have a significant role in the diagnosis of this fatal disease.
View details for DOI 10.1371/journal.pone.0148911
View details for Web of Science ID 000371219000032
View details for PubMedID 26882224
Intraoperative Tracheal Injury
THORACIC SURGERY CLINICS
2015; 25 (3): 249-?
Intraoperative tracheal injury is a rare but potentially devastating complication. Transhiatal esophagectomy should be avoided in patients with proximal esophageal tumors who underwent neoadjuvant therapy, and percutaneous tracheostomy should be avoided in patients with short, thick necks. Early recognition leads to improved outcomes. Patients present with a sudden loss in airway pressure, air leaking into the operative field, or mediastinal and subcutaneous emphysema. Treatment starts with airway control. Primary buttressed repair is recommended, through either a left cervical incision for proximal injuries or a right thoracotomy for distal injuries. Nonoperative management has been used safely in select patients injured during intubation or tracheostomy.
View details for DOI 10.1016/j.thorsurg.2015.04.008
View details for Web of Science ID 000359891100004
View details for PubMedID 26210921
Wnt7A is a putative prognostic and chemosensitivity marker in human malignant pleural mesothelioma.
2015; 33 (4): 2052–60
Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that has a poor prognosis, limited treatment options, and a worldwide incidence that is expected to increase in the next decade. We evaluated Wnt7A expression in 50 surgically resected tumor specimens using quantitative PCR. The expression values, were assessed by clinicopathological factors and K-M and Cox's regression with OS. The mean level of Wnt7A expression had a significant correlation with International Mesothelioma Interest Group (IMIG) stage (P<0.034), gender, smoking history and ethnicity, respectively (P=0.020, P=0.014, P=0.039). In the univariate analysis, low Wnt7A expression was a significant negative factor for overall survival (P=0.043, HR=2.30). However, multivariate Cox's regression revealed no significant factors for overall survival (low Wnt7A: P=0.051, HR=2.283; non-epithelioid subtype: P=0.050, HR=2.898). In patients with epithelioid tumors, those with low Wnt7A expression had significantly worse prognosis (P=0.019, HR=2.98). In patients with epithelioid tumors, females had significantly better prognosis than males (P=0.035). In patients who did not have neoadjuvant chemotherapy, prognosis was significantly more favorable for patients with high Wnt7A expression than for those with low Wnt7A expression (P=0.031). Among the patients with low Wnt7A-expressing tumors, those who received neoadjuvant chemotherapy had better prognosis than those who did not (P=0.024). The results of our study suggest that Wnt7A expression is a putative prognostic factor and a predictor of chemosensitivity.
View details for DOI 10.3892/or.2015.3771
View details for PubMedID 25632963
View details for PubMedCentralID PMC4358089
Gli as a Novel Therapeutic Target in Malignant Pleural Mesothelioma
2013; 8 (3)
Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis. Current treatment is rarely curative, thus novel meaningful therapies are urgently needed. Inhibition of Hedgehog (Hh) signaling at the cell membrane level in several cancers has shown anti-cancer activity in recent clinical studies. Evidence of Hh-independent Gli activation suggests Gli as a more potent therapeutic target. The current study is aimed to evaluate the potential of Gli as a therapeutic target to treat MPM. The expression profiles of Gli factors and other Hh signaling components were characterized in 46 MPM patient tissue samples by RT-PCR and immunohistochemistry. Cultured cell lines were employed to investigate the requirement of Gli activation in tumor cell growth by inhibiting Gli through siRNA or a novel small molecule Gli inhibitor (Gli-I). A xenograft model was used to evaluate Gli-I in vivo. In addition, a side by side comparison between Gli and Smoothened (Smo) inhibition was conducted in vitro using siRNA and small molecule inhibitors. Our study reported aberrant Gli1 and Gli2 activation in a large majority of tissues. Inhibition of Gli by siRNAs or Gli-I suppressed cell growth dramatically both in vitro and in vivo. Inhibition of Gli exhibited better cytotoxicity than that of Smo by siRNA and small molecule inhibitors vismodegib and cyclopamine. Combination of Gli-I and pemetrexed, as well as Gli-I and vismodegib demonstrated synergistic effects in suppression of MPM proliferation in vitro. In summary, Gli activation plays a critical role in MPM. Inhibition of Gli function holds strong potential to become a novel, clinically effective approach to treat MPM.
View details for DOI 10.1371/journal.pone.0057346
View details for Web of Science ID 000316936100019
View details for PubMedID 23483902
View details for PubMedCentralID PMC3590216
SMO expression level correlates with overall survival in patients with malignant pleural mesothelioma.
Journal of experimental & clinical cancer research : CR
2013; 32: 7
Malignant mesothelioma is an aggressive, treatment-resistant tumor arising from mesothelium of pleura, peritoneum and pericardium. Despite current combined regimen, its prognosis remains dismal, calling for more effective targeted therapies. We investigated whether aberrant Hh activation may play a role in mesothelioma.SMO and SHH expression levels were analyzed in 46 mesothelioma tissue specimens with real-time RT-PCR, and correlation with survival was analyzed with univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival curves, and the log-rank test. We also examined multiple mesothelioma cell lines for SMO expression and the effect of Hh inhibition by a specific SMO antagonist on cell proliferation by MTS assay.We observed strong correlation between higher SMO and SHH expression levels with poorer overall survival. Remarkably, Hh inhibition by a specific SMO inhibitor significantly suppressed cell proliferation in the mesothelioma cell lines examined.Our data strongly support that Hh signaling deregulation plays critical roles in proliferation of mesothelioma, and consistently exerts significant impact on prognosis of the disease. Therefore our findings revealed the hitherto unappreciated role of Hh activation in mesothelioma, and pinpointed Hh signaling antagonist as a potential new therapy against this devastating disease.
View details for DOI 10.1186/1756-9966-32-7
View details for PubMedID 23379358
View details for PubMedCentralID PMC3622612
SULF2 expression by immunohistochemistry and overall survival in oesophageal cancer: a cohort study
2012; 2 (6)
Oesophageal cancer is the eighth most commonly diagnosed cancer worldwide, and there is a need for biomarkers to improve diagnosis, prognosis and treatment. Sulfatases 2 (SULF2) is an extracellular endosulphatase that regulates several signalling pathways in carcinogenesis and has been associated with poor prognosis. This study evaluates the relationship between SULF2 expression by immunohistochemistry and overall survival in patients with oesophageal cancer.Cohort study.Single tertiary care centre.We included patients who underwent esophagectomy for invasive oesophageal adenocarcinoma and squamous cell carcinoma at a tertiary care centre from 1997 to 2006. We excluded patients with recurrent oesophageal cancer or less than 3 mm invasive tumour on H&E stained slide. A section from each paraffin-embedded tissue specimen was stained with an anti-SULF2 monoclonal antibody.A pathologist blinded to overall survival determined the percentage and intensity of tumour cells staining. Vital status was obtained through the Social Security Death Master File, and overall survival was calculated from the date of surgery.One-hundred patients with invasive oesophageal cancer were identified, including 75 patients with adenocarcinoma and 25 patients with squamous cell carcinoma. The squamous cell carcinoma samples had a higher mean percentage and intensity of tumour cells staining compared with the adenocarcinoma samples. After adjusting for age, sex, race, histological type, stage and neoadjuvant therapy, for every 10% increase in percentage of tumour cells staining for SULF2, the HR for death increased by 13% (95% CI 1.01 to 1.25; p=0.03).The majority of adenocarcinoma samples and all of the squamous cell carcinoma samples had SULF2 staining. The percentage of tumour cells staining for SULF2 was significantly associated with overall survival. Thus, SULF2 is a potential biomarker in oesophageal cancer and may have an important role in the management of patients with this disease.
View details for DOI 10.1136/bmjopen-2012-001624
View details for Web of Science ID 000315081400071
View details for PubMedID 23180455
A somatic TSHR mutation in a patient with lung adenocarcinoma with bronchioloalveolar carcinoma, coronary artery disease and severe chronic obstructive pulmonary disease.
2012; 28 (4): 1225–30
In a screen for thoracic malignancy-associated markers, thyroid stimulating hormone receptor (TSHR) was identified as a candidate as it binds to the previously-characterized lung cancer marker NKX2-1. We screened for mutations in all coding regions of the TSHR gene in 96 lung adenocarcinoma samples and their matched adjacent normal lung samples. We found one patient with a somatic mutation at codon 458 (exon 10), which is located at the transmembrane domain where most TSHR mutations have been found in thyroid-related diseases. This patient had lung adenocarcinoma with BAC (bronchioloalveolar carcinoma) features in the setting of a prior medical history significant for carotid stenosis and severe chronic obstructive pulmonary disease (COPD). In order to characterize the genetic features of TSHR in lung cancer, we checked for TSHR expression and copy number in the 96 lung cancer tissues. TSHR protein expression was generally overexpressed in multiple thoracic malignancies (adenocarcinoma, squamous cell carcinoma and malignant pleural mesothelioma) by immunohistochemistry. Our data suggest that aberrant TSHR function may contribute to lung cancer development or a subgroup of lung cancer with specific clinical phenotypes.
View details for DOI 10.3892/or.2012.1938
View details for PubMedID 22842620