Aliya N Husain

University of Chicago, Chicago, Illinois, United States

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Publications (129)590.72 Total impact

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    ABSTRACT: OBJECTIVES The tumour/node/metastasis (TNM) staging system for malignant pleural mesothelioma (MPM) is a worldwide standard, but has many limitations. Tumour volume has been suggested as a predictor of survival. Due to the complex anatomy, estimation of tumour volume via CT scan can be challenging. Surgical volume may be more accurate. Therefore, we prospectively determined resected specimen volumes and weights in consecutive patients undergoing extended pleurectomy and decortication (EPD) and correlated this with overall survival and T and N stage.
    No preview · Article · Jan 2016 · European Journal of Cardio-Thoracic Surgery
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    Preview · Article · Dec 2015 · Journal of Cardiothoracic Surgery
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    ABSTRACT: BRCA-associated protein 1 (BAP1) has emerged as a promising biomarker for malignant pleural mesothelioma (MPM). Loss of BAP1 expression can occur by a variety of mechanisms, but reports on incidence are variable and the clinical significance is unclear. In order to investigate the diagnostic and prognostic significance of BAP1, we constructed a tissue microarray consisting of 111 MPM cases and performed BAP1 immunohistochemistry. BAP1 was lost in 77% of epithelioid cases (n=58) but was retained in all sarcomatoid cases (n=10); 49% of biphasic cases showed loss (n=43), and BAP1-negative cases demonstrated loss of staining in both the epithelioid and sarcomatoid components. All non-neoplastic mesothelial tissues (n=20) retained BAP1, resulting in a sensitivity, specificity, positive predictive value, and negative predictive value of 61%, 100%, 100%, and 32%, respectively. Moreover, BAP1 expression in spindled mesothelium enabled discrimination of reactive and malignant cells, thus providing a more objective means of distinguishing epithelioid from biphasic morphology compared to histology alone. Nonetheless, BAP1 staining was patchy in some benign mesothelial neoplasms, which raises concern for using BAP1 in small biopsies. Kaplan-Meier analysis demonstrated a significant improvement in overall survival with BAP1 loss, but this did not reach significance in multivariate analysis accounting for histologic subtype. When only epithelioid cases were analyzed there was a trend toward increased survival, but it did not reach significance. We conclude that BAP1 loss is frequent in epithelioid MPM, which is in turn associated with improved survival, and that it can have additional clinical significance by facilitating histologic classification.
    No preview · Article · Sep 2015 · Human pathology
  • Stephanie M. McGregor · Aliya N. Husain
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    ABSTRACT: Arrhythmogenic cardiomyopathy (AC) has traditionally been regarded as a rare disease with variably penetrant autosomal-dominant inheritance. Recent years have revealed that AC is actually a spectrum of disease with prevalence much higher than previously thought. Diagnosis can be quite challenging because of highly variable clinical presentation, even among family members sharing a mutation. Unlike other cardiomyopathies, AC has a concealed phase during which patients have arrhythmias in the absence of structural heart disease but remain at risk of sudden cardiac death. Importantly, it is in the setting of sudden cardiac death that pathologists are most likely to encounter AC. It is critical that these findings not be overlooked, as family members of the deceased may also be affected and could potentially avoid such a dismal outcome. With time, advances in ancillary studies are likely to expand the role for pathologists in AC diagnosis.
    No preview · Article · Sep 2015 · Archives of pathology & laboratory medicine
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    Preview · Article · Aug 2015
  • Qudsia Arif · Aliya N Husain
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    ABSTRACT: Context .- Malignant mesothelioma is a relatively rare pleural tumor that may mimic benign mesothelial lesions and various other tumors including carcinomas and sarcomas. This makes the diagnosis challenging for the pathologist. Objective .- To provide a brief but useful update on the immunohistochemical, cytogenetic, and molecular markers that are currently available for the diagnosis of malignant mesothelioma. Data Sources .- Reference materials including peer-reviewed publications, text books, and consensus opinion reports among pathologists. Conclusions .- It is important to correlate histologic findings on adequate biopsy samples with clinical and radiologic features. Useful diagnostic mesothelial markers include calretinin, WT-1, cytokeratin 5/6, and D2-40 (podoplanin). It is recommended that at least 2 mesothelial and 2 carcinoma markers with greater than 80% sensitivity and specificity be used for the diagnosis of mesothelioma when all clinical, radiologic, and histologic features are concordant. p16 deletion is reported in up to 70% of primary epithelioid and 90% to 100% of sarcomatoid pleural mesotheliomas. Presence of this homozygous gene deletion is so far the best indicator of mesothelioma. To date, this deletion has not been reported in any benign mesothelial lesion. The impact of various histologic patterns on the clinical and prognostic aspects of mesothelioma is addressed. The pleomorphic pattern, when present in more than 10% of tumor, translates into a highly aggressive behavior and is associated with poor survival. Recent studies have shown that the high-grade subgroup of deciduoid mesothelioma with pleomorphic histologic pattern also has a more aggressive clinical course. Nuclear grade (combination of nuclear atypia and mitotic count) may also prove to be an independent prognostic factor.
    No preview · Article · Aug 2015 · Archives of pathology & laboratory medicine
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    ABSTRACT: We describe a case of cardiac toxoplasmosis diagnosed by routine endomyocardial biopsy in a patient with trimethoprim-sulfamethoxazole (TMP-SMX) intolerance on atovaquone prophylaxis. Data are not available on the efficacy of atovaquone as Toxoplasma gondii prophylaxis after heart transplantation. In heart transplant patients in whom TMP-SMX is not an option, other strategies may be considered, including the addition of pyrimethamine to atovaquone. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jun 2015 · Transplant Infectious Disease
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    ABSTRACT: To determine the potential utility of computed tomography (CT) scans in the assessment of physical tumor bulk in malignant pleural mesothelioma patients. Twenty-eight patients with malignant pleural mesothelioma were used for this study. A CT scan was acquired for each patient prior to surgical resection of the tumor (median time between scan and surgery: 27 days). After surgery, the ex-vivo tumor volume was measured by a pathologist using a water displacement method. Separately, a radiologist identified and outlined the tumor boundary on each CT section that demonstrated tumor. These outlines then were analyzed to determine the total volume of disease present, the number of sections with outlines, and the mean volume of disease per outlined section. Subsets of the initial patient cohort were defined based on these parameters, i.e. cases with at least 30 sections of disease with a mean disease volume of at least 3mL per section. For each subset, the R- squared correlation between CT-based tumor volume and physical ex-vivo tumor volume was calculated. The full cohort of 28 patients yielded a modest correlation between CT-based tumor volume and the ex-vivo tumor volume with an R-squared value of 0.66. In general, as the mean tumor volume per section increased, the correlation of CT-based volume with the physical tumor volume improved substantially. For example, when cases with at least 40 CT sections presenting a mean of at least 2mL of disease per section were evaluated (n=20) the R-squared correlation increased to 0.79. While image-based volumetry for mesothelioma may not generally capture physical tumor volume as accurately as one might expect, there exists a set of conditions in which CT-based volume is highly correlated with the physical tumor volume. SGA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology.
    No preview · Article · Jun 2015 · Medical Physics
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    ABSTRACT: Tumor volume promises to become a more important factor in patient management. Mesothelioma, with its unique morphology and complex growth pattern, presents a challenging target for tumor volumetrics derived from computed tomography (CT) scans. This study evaluated the validity of image-based mesothelioma tumor volume against the physical volume of the tumor bulk captured by the images. Twenty-eight patients underwent CT scanning prior to pleurectomy/decortication with an intent to achieve a macroscopic complete resection. A radiologist manually outlined the tumor border in all CT sections in which tumor appeared in the pre-surgery scan. CT-based tumor volume was computed as the number of image pixels enclosed by all tumor outlines across all sections in the scan multiplied by the physical dimensions of the voxel of tissue captured by each image pixel. The gross tumor specimen volume was measured ex vivo through a water-displacement technique. Correlation between CT volume and pathology volume was calculated. A correlation coefficient r-squared value of 0.66 was found between CT-based tumor volume and gross tumor specimen volume. Differences between the mean volume (either CT volume or pathology volume) across tumors of different T stages did not achieve statistical significance. Despite a modest correlation between CT-based tumor volume and gross tumor specimen volume, image-based volumetry for mesothelioma is not straightforward-perhaps, in part, due to the challenges of distinguishing tumor borders from adjacent structures and perhaps, in part, due to a complex pathologic reference standard. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Jan 2015 · Lung cancer (Amsterdam, Netherlands)
  • Marina Ivanovic · Husain A. Sattar · Mario Moric · Aliya N. Husain
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    ABSTRACT: Introduction: Bronchus-associated lymphoid tissue (BALT) is part of the lung immune system that consists of small aggregates of lymphoid cells at the bifurcation of the airways and along the lymphatic routes. While in animal models it plays a role in allograft response, that relationship has never been established in humans. BALT is often seen in lung transplant biopsies evaluated for rejection especially in A0 and A1 rejection. In early post-transplant biopsies (first 180 days) it is more commonly seen with A2 and A3 rejection. Irrespective of its role in allograft response in humans, morphologically BALT can occasionally be difficult to distinguish from rejection. Methods: We analyzed 33 transbronchial transplant lung biopsies, 25 with BALT and 8 with rejection for presence of CD21 positive dendritic cells to determine if their presence can distinguish BALT from the acute rejection. Fisher's exact test was used to evaluate statistical significance. Results: Of the 25 biopsies with BALT, 20 (80%) stained positive for CD21, while none of the 8 biopsies with acute rejection stained positive for CD21 (0%), a significant difference (p value <0.0001). Discussion: The results of the study showed that CD21 antibody may be helpful in distinguishing BALT from acute rejection in difficult cases.
    No preview · Article · Oct 2014 · Pathology

  • No preview · Article · Oct 2014 · Cancer Research
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    ABSTRACT: Malignant pleural mesothelioma (MPM) is an aggressive disease with a poor prognosis. Studies have shown that both MET and its key downstream intracellular signaling partners, PI3K and mTOR, are overexpressed in MPM. Here we determined the combinatorial therapeutic efficacy of a new generation small molecule inhibitor of MET, ARQ 197, and dual PI3K/mTOR inhibitors NVP-BEZ235 and GDC-0980 in mesothelioma cell and mouse xenograft models. Cell viability results show that mesothelioma cell lines were sensitive to ARQ 197, NVP-BEZ235 and GDC-0980 inhibitors. The combined use of ARQ 197 with either NVP-BEZ235 or GDC-0980, was synergistic (CI<1). Significant delay in wound healing was observed with ARQ 197 (p<0.001) with no added advantage of combining it with either NVP-BEZ235 or GDC-0980. ARQ 197 alone mainly induced apoptosis (20±2.36%) that was preceded by suppression of MAPK activity, while all the three suppressed cell cycle progression. Both GDC-0980 and NVP-BEZ235 strongly inhibited activities of PI3K and mTOR as evidenced from the phosphorylation status of AKT and S6 kinase. The above observation was further substantiated by the finding that a majority of the MPM archival samples tested revealed highly active AKT. While the single use of ARQ 197 and GDC-0980 inhibited significantly the growth of MPM xenografts (p<0.05, p<0.001 respectively) in mice, the combination of the above two drugs was highly synergistic (p<0.001). Our results suggest that the combined use of ARQ 197/NVP-BEZ235 and ARQ 197/GDC-0980 is far more effective than the use of the drugs singly in suppressing MPM tumor growth and motility and therefore merit further translational studies.
    Full-text · Article · Sep 2014 · PLoS ONE
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    ABSTRACT: Objectives: To examine carbonic anhydrase IX (CAIX), a marker of renal cell carcinoma that recently has been described in malignant effusions. Methods: Pleural and peritoneal fluids with the following diagnoses-reactive (n = 23), carcinoma (n = 17), and "suspicious for mesothelioma" (n = 4)-were immunostained for CAIX, calretinin, Ber-EP4, and MOC31. A tissue microarray of epithelioid (n = 27) and sarcomatoid (n = 8) mesotheliomas and three cases of benign mesothelium were also immunostained for CAIX. Results: Mesothelial cells in both reactive (18/23) and malignant effusions (18/21) were positive for CAIX (P > .05). In carcinomatous effusions, CAIX expression was restricted to the mesothelial cells. Agreement between CAIX and calretinin expression was present in 89% of cases. In tissues, CAIX was positive in 100% of benign and 91% of malignant mesothelium. Conclusions: CAIX can be a useful ancillary marker for identifying mesothelial cells. There is no difference in CAIX expression between benign and malignant mesothelium. Caution should be exercised while evaluating for metastasis from renal cell carcinoma.
    Preview · Article · Jul 2014 · American Journal of Clinical Pathology
  • John J Cardasis · Heber MacMahon · Aliya N Husain
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    ABSTRACT: Introduction: Chronic aspiration of small volumes of oral and gastric contents can lead to lung disease. This process is less familiar than the acute aspiration syndromes, which can create confusion in terminology as well as with radiologic and pathologic definitions. Objectives: In this study we analyze a series of cases of patients with chronic occult aspiration to better define the disease process. Methods: Twenty-five patients with chronic occult aspiration as defined pathologically on lung biopsy were studied by means of retrospective review of their case records. Clinical associations and radiologic and pathologic patterns were noted. Measurements & Main Results: Among patients with chronic occult aspiration, there was a high prevalence of gastroesophageal reflux disease (96%), esophageal dysfunction (40%), oropharyngeal/laryngeal dysfunction (40%), hiatal hernias (32%), obstructive sleep apnea (32%) and obesity (52%). The radiologic presentation was typically one of multilobar centrilobular nodularity, tree-in-bud and airway thickening with a subset of patients having evidence of fibrosis. The disease presented pathologically with exogenous lipoid pneumonia, poorly formed granulomas and foreign body-type multinucleated giant cells with or without foreign material. Pathologic fibrosis was also seen. Conclusion: In this study, chronic occult aspiration was associated with a number of comorbid conditions and a spectrum of radiologic and pathologic patterns, which in some patients included fibrosis.
    No preview · Article · Jun 2014
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    ABSTRACT: Transthyretin (TTR) cardiac amyloidosis is characterized by deposition of either mutant or wild type TTR amyloid protein in the myocardium ultimately leading to progressive cardiomyopathy and heart failure. The most common TTR gene mutation that leads to TTR cardiac amyloidosis is the valine-to-isoleucine substitution at position 122 (V122I or Ile122). Currently, the only definitive treatment suggested for mutant TTR cardiac amyloidosis is the combined or sequential liver-heart transplantation in eligible patients, since liver is the source of TTR production. Here, we report a case of heterozygous Val122L mutated TTR-related cardiac amyloidosis treated with isolated heart transplantation with no recurrence of amyloid in the cardiac allograft and no systemic abnormalities 5 years after heart transplantation.AbbreviationsMMFmycophenolate mofetilNYHANew York Heart AssociationTTRtransthyretinVEminute ventilation
    No preview · Article · Jun 2014 · Amyloid
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    ABSTRACT: Non-small cell lung cancers (NSCLC) are highly heterogeneous at the molecular level and comprise 75% of all lung tumors. We have previously shown that the receptor tyrosine kinase (RTK) MET frequently suffers gain-of-function mutations that significantly promote lung tumorigenesis. Subsequent studies from our lab also revealed that PAX5 transcription factor is preferentially expressed in small cell lung cancer (SCLC) and promotes MET transcription. PAX8, however, is also expressed in NSCLC cell lines. We therefore investigated the role of PAX8 in NSCLC. Using IHC analysis, PAX8 protein expression was determined in archival NSCLC tumor tissues (n = 254). In order to study the effects of PAX8 knockdown on NSCLC cellular functions such as apoptosis and motility, siRNA against PAX8 was used. Confocal fluorescence microscopy was used to monitor the localization of MET, RON and PAX8. The combinatorial effect of PAX8 knockdown and MET inhibition using SU11274 was investigated in NSCLC cell viability assay. Relative levels of PAX8 protein were elevated (>= + 2 on a scale of 0-3) in adenocarcinoma (58/94), large cell carcinoma (50/85), squamous cell carcinoma (28/47), and metastatic NSCLC (17/28; lymph node). Utilizing early progenitors isolated from NSCLC cell lines and fresh tumor tissues, we observed robust overexpression of PAX8, MET, and RON. PAX8 knockdown A549 cells revealed abrogated PAX8 expression with a concomitant loss in MET and the related RON kinase expression. A dramatic colocalization between the active form of MET (also RON) and PAX8 upon challenging A549 cells with HGF was visualized. A similar colocalization of MET and EGL5 (PAX8 ortholog) proteins was found in embryos of C. elegans. Most importantly, knockdown of PAX8 in A549 cells resulted in enhanced apoptosis (~ 6 fold) and decreased cell motility (~45%), thereby making PAX8 a potential therapeutic target. However, the combinatorial approach of PAX8 knockdown and treatment with MET inhibitor, SU11274, had marginal additive effect on loss of NSCLC cell viability. PAX8 provides signals for growth and motility of NSCLC cells and is necessary for MET and RON expression. Further investigations are necessary to investigate the therapeutic potential of PA8 in NSCLC.
    Full-text · Article · Mar 2014 · BMC Cancer
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    Aliya N Husain

    Preview · Article · Feb 2014 · American Journal of Clinical Pathology
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    ABSTRACT: Small cell lung cancer (SCLC) is a devastating disease and current therapies have not greatly improved the 5-year survival rates. Topoisomerase (Top) inhibition is a treatment modality for SCLC; however, the response is short lived. Consequently, our research has focused on improving SCLC therapeutics through the identification of novel targets. Previously, we identified MET to be overexpressed and functional in SCLC. Herein, we investigated the therapeutic potential of combinatorial targeting of MET using SU11274 and Top1 using 7-ethyl-10-hydroxycamptothecin (SN-38). MET and TOP1 gene copy numbers and protein expression were determined in 29 patients with limited (n=11) and extensive (n=18) disease. MET gene copy number was significantly increased (>6 copies) in extensive disease compared to limited disease (p=0.015). Similar TOP1 gene copy numbers were detected in limited and extensive disease. Immunohistochemical staining revealed significantly higher Top1 nuclear expression in extensive (0.93) versus limited (0.15) disease (p=0.04). Interestingly, a significant positive correlation was detected between MET gene copy number and Top1 nuclear expression (r=0.5). In vitro stimulation of H82 cells revealed HGF-induced nuclear co-localization of p-MET and Top1. Furthermore, activation of the HGF/MET axis enhanced Top1 activity, which was abrogated by SU11274. Combination of SN-38 with SU11274 dramatically decreased SCLC growth as compared to either drug alone. Collectively, these findings suggest that combinatorial inhibition of MET and Top1 is a potentially efficacious treatment strategy for SCLC.
    Full-text · Article · Dec 2013 · Molecular Cancer Therapeutics
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    ABSTRACT: Lung cancer is a heterogeneous disease encompassing a wide array of genetic abnormalities. The MET receptor tyrosine kinase is altered in many lung cancers, especially non-small cell lung cancer (NSCLC), and clinical trials of MET inhibitors that are underway are documenting cases of acquired resistance. Based on evidence that the RON tyrosine kinase receptor can also be overexpressed in NSCLC, we evaluated the potent MET/RON dual kinase inhibitor LY2801653 in this setting. LY2801653 was more efficacious than the MET/ALK/RON/ROS inhibitor crizotinib with a distinct pattern of downstream signaling effects. Using the PamGene platform, we found that inhibition of MET and RON was associated with decreased phosphorylation of CBL, PI3K and STAT3. In classical and orthotopic mouse xenograft models of lung cancer, LY2801653 decreased tumor growth, dramatically inhibiting mitotic events and angiogenesis. Taken together, our results argued that specific targeting of the MET/RON kinases could provide robust inhibition of cell proliferation and tumor outgrowth in multiple in vitro and in vivo models of NSCLC. These findings offer a robust preclinical proof of concept for MET/RON targeting by LY2801653 as a promising small molecule modality to treat NSCLC.
    Full-text · Article · Dec 2013 · Cancer Research
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    ABSTRACT: World-wide, esophageal cancer is a growing epidemic and patients frequently present with advanced disease that is surgically inoperable. Hence, chemotherapy is the predominate treatment. Cytotoxic platinum compounds are mostly used, but their efficacy is only moderate. Newer alkylating agents have shown promise in other tumor types, but little is known about their utility in esophageal cancer. We utilized archived human esophageal cancer samples and esophageal cancer cell lines to evaluate O-6-methylguanine-deoxyribonucleic acid methyltransferase (MGMT) hypermethylation status and determined sensitivity to the alkylating drug temozolomide (TMZ). Immunoblot analysis was performed to determine MGMT protein expression in cell lines. To assess and confirm the effect of TMZ treatment in a methylated esophageal cancer cell line in vivo, a mouse flank xenograft tumor model was utilized. Nearly 71% (12/17) of adenocarcinoma and 38% (3/8) of squamous cell carcinoma (SCC) patient samples were MGMT hypermethylated. Out of four adenocarcinoma and nine SCC cell lines tested, one of each histology was hypermethylated. Immunoblot analyses confirmed that hypermethylated cell lines did not express the MGMT protein. In vitro cell viability assays showed the methylated Kyse-140 and FLO cells to be sensitive to TMZ at an IC50 of 52-420 μM, whereas unmethylated cells Kyse-410 and SKGT-4 did not respond. In an in vivo xenograft tumor model with Kyse-140 cells, which are MGMT hypermethylated, TMZ treatment abrogated tumor growth by more than 60%. MGMT methylation may be an important biomarker in subsets of esophageal cancers and targeting by TMZ may be utilized to successfully treat these patients.
    No preview · Article · Oct 2013 · Journal of Carcinogenesis

Publication Stats

3k Citations
590.72 Total Impact Points

Institutions

  • 2007-2015
    • University of Chicago
      • Department of Pathology
      Chicago, Illinois, United States
    • Roswell Park Cancer Institute
      Buffalo, New York, United States
  • 2010
    • The University of Chicago Medical Center
      • Department of Pathology
      Chicago, Illinois, United States
  • 2008
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2005
    • Harvard University
      Cambridge, Massachusetts, United States
    • University of Toronto
      • Department of Laboratory Medicine and Pathobiology
      Toronto, Ontario, Canada
  • 2002
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
  • 1988-2002
    • Loyola University Medical Center
      • • Department of Pathology
      • • Department of Radiology
      Maywood, Illinois, United States