Person:
Barletta, Justine

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Barletta

First Name

Justine

Name

Barletta, Justine
Author's Publications: search.filters.isAuthorOfPublication.ca065233-47bb-4871-979c-de86309b8d24

Search Results

Now showing 1 - 7 of 7
  • Thumbnail Image
    Publication
    The variable phenotype and low-risk nature of RAS-positive thyroid nodules
    (BioMed Central, 2015) Medici, Marco; Kwong, Norra; Angell, Trevor E.; Marqusee, Ellen; Kim, Matthew; Frates, Mary; Benson, Carol; Cibas, Edmund; Barletta, Justine; Krane, Jeffrey; Ruan, Daniel T.; Cho, Nancy; Gawande, Atul; Moore, Francis; Alexander, Erik
    Background: Oncogenic mutations are common in thyroid cancers. While the frequently detected RAS-oncogene mutations have been studied for diagnostic use in cytologically indeterminate thyroid nodules, no investigation has studied such mutations in an unselected population of thyroid nodules. No long-term study of RAS-positive thyroid nodules has been performed. Methods: We performed a prospective, blinded cohort study in 362 consecutive patients presenting with clinically relevant (>1 cm) thyroid nodules. Fine needle aspiration cytology and mutational testing were obtained for all nodules. Post-operative histopathology was obtained for malignant or indeterminate nodules, and benign nodules were sonographically followed. Histopathological features were compared between RAS- and BRAF-positive malignancies. RAS-positive benign nodules were analyzed for growth or cellular change from prior aspirations. Results: Overall, 17 of 362 nodules were RAS-positive. Nine separate nodules were BRAF-positive, of which eight underwent surgery and all proved malignant (100 %). Out of the 17 RAS-positive nodules, ten underwent surgery, of which eight proved malignant (47 %). All RAS-positive malignancies were low risk – all follicular variants of papillary carcinoma, without extrathyroidal extension, metastases, or lymphovascular invasion. RAS-positivity was associated with malignancy in younger patients (P = 0.028). Of the nine RAS-positive benign nodules, five had long-term prospective sonographic follow-up (mean 8.3 years) showing no growth or signs of malignancy. Four of these nodules also had previous aspirations (mean 5.8 years prior), all with similar benign results. Conclusions: While RAS-oncogene mutations increase malignancy risk, these data demonstrate a low-risk phenotype for most RAS-positive cancers. Furthermore, cytologically benign, yet RAS-positive nodules behave in an indolent fashion over years. RAS-positivity alone should therefore not dictate clinical decisions.
  • Thumbnail Image
    Publication
    FGFR3 expression in primary and metastatic urothelial carcinoma of the bladder
    (BlackWell Publishing Ltd, 2014) Guancial, Elizabeth A; Werner, Lillian; Bellmunt, Joaquim; Bamias, Aristotle; Choueiri, Toni K; Ross, Robert; Schutz, Fabio A; Park, Rachel S; O'Brien, Robert J; Hirsch, Michelle; Barletta, Justine; Berman, David M; Lis, Rosina; Loda, Massimo; Stack, Edward C; Garraway, Levi A; Riester, Markus; Michor, Franziska; Kantoff, Philip W; Rosenberg, Jonathan E
    While fibroblast growth factor receptor 3 (FGFR3) is frequently mutated or overexpressed in nonmuscle-invasive urothelial carcinoma (UC), the prevalence of FGFR3 protein expression and mutation remains unknown in muscle-invasive disease. FGFR3 protein and mRNA expression, mutational status, and copy number variation were retrospectively analyzed in 231 patients with formalin-fixed paraffin-embedded primary UCs, 33 metastases, and 14 paired primary and metastatic tumors using the following methods: immunohistochemistry, NanoString nCounterTM, OncoMap or Affymetrix OncoScanTM array, and Gain and Loss of Analysis of DNA and Genomic Identification of Significant Targets in Cancer software. FGFR3 immunohistochemistry staining was present in 29% of primary UCs and 49% of metastases and did not impact overall survival (P = 0.89, primary tumors; P = 0.78, metastases). FGFR3 mutations were observed in 2% of primary tumors and 9% of metastases. Mutant tumors expressed higher levels of FGFR3 mRNA than wild-type tumors (P < 0.001). FGFR3 copy number gain and loss were rare events in primary and metastatic tumors (0.8% each; 3.0% and 12.3%, respectively). FGFR3 immunohistochemistry staining is present in one third of primary muscle-invasive UCs and half of metastases, while FGFR3 mutations and copy number changes are relatively uncommon.
  • Thumbnail Image
    Publication
    Sox2 Protein Expression is an Independent Poor Prognostic Indicator in Stage I Lung Adenocarcinoma
    (Ovid Technologies (Wolters Kluwer Health), 2010) Sholl, Lynette; Barletta, Justine; Yeap, Beow; Chirieac, Lucian; Hornick, Jason
    Many patients with stage I non-small cell lung carcinoma will develop recurrence following surgical excision. Sox2 is a marker of embryonic stem cell pluripotency that is associated with aggressive tumor behavior and is expressed in a subset of lung adenocarcinomas. We hypothesized that Sox2 expression may provide prognostic information in early stage lung adenocarcinomas. We evaluated formalin-fixed paraffin embedded tissue from 104 stage I lung adenocarcinomas resected between 1997 and 2000. Sox2 expression was analyzed by immunohistochemistry and compared to clinicopathologic features, time-to-progression (TTP) and overall survival (OS). Sox2 expression was detected in 50% of cases and was more frequent in tumors from older and male patients but not significantly associated with smoking status, tumor stage, grade, or histologic subtype. Compared to Sox2-negative tumors, Sox2 expression predicted a shorter TTP (49% versus 82% at 5 years; P = 0.0006) and shorter OS (54% versus 79% at 5 years; P = 0.004). By multivariate analysis, Sox2 expression predicted a greater risk of progression among men (hazard ratio [HR] 5.6; 95% CI 2.3 to 13.8) and women (HR 2.1; 95% CI 0.8 to 5.7). Sox2 expression was associated with significantly shorter OS among men (HR 2.5; 95% CI 1.2 to 5.1), but not in women. Sox2 appears to be an independent predictor of poor outcome in stage I lung adenocarcinomas and may help stratify patients at increased risk for recurrence.
  • No Thumbnail Available
    Publication
    Collagen XXIII: A Potential Biomarker for the Detection of Primary and Recurrent Non–Small Cell Lung Cancer
    (American Association for Cancer Research (AACR), 2010-05) Spivey, Kristin A.; Banyard, Jacqueline; Solis, Luisa M.; Wistuba, Ignacio I.; Barletta, Justine; Gandhi, Leena; Feldman, Henry; Rodig, Scott; Chirieac, Lucian; Zetter, Bruce
    Background Collagen XXIII is a transmembrane collagen previously shown to be upregulated in metastatic prostate cancer. This study’s purpose was to determine the protein expression of collagen XXIII in tumor tissues from a variety of cancers and to assess collagen XXIII’s utility as a biomarker for non small-cell lung cancer (NSCLC). Methods A multi-cancer tissue microarray (TMA) was used for immunohistochemical examination of collagen XXIII protein expression in a variety of cancers. Subsequently, collagen XXIII expression was analyzed in three separate cohorts using TMAs with representative tumor and control lung tissues from NSCLC patients. In addition, NSCLC patient urine samples were analyzed for the presence of collagen XXIII via Western blot. Results Collagen XXIII was present in tissue samples from a variety of cancers. Within lung cancer tissues, collagen XXIII staining was enriched in NSCLC subtypes. Collagen XXIII was present in 294 of 333 (88%) lung adenocarcinomas and 97 of 133 (73%) squamous cell carcinomas (SqCC). In urine, collagen XXIII was present in 23 of 29 (79%) NSCLC patient samples but only in 15 of 54 (28%) control samples. High collagen XXIII staining intensity correlated with shorter recurrence-free survival in NSCLC patients. Conclusions We demonstrate the capability of collagen XXIII as a tissue and urinary biomarker for NSCLC, where positivity in tissue or urine significantly correlates with presence of NSCLC and high staining intensity is a significant recurrence predictor. Impact Inclusion of collagen XXIII in a tissue or urine-based cancer biomarker panel could inform NSCLC patient treatment decisions.
  • No Thumbnail Available
    Publication
    The Prognostic Significance of Grading in Lung Adenocarcinoma
    (2010-02-01) Barletta, Justine; Yeap, Beow; Chirieac, Lucian
    Background Although grading has prognostic significance for many tumor types, a prognostically significant grading system for lung adenocarcinoma has not yet been established. The aim of this study was to evaluate histologic characteristics included in tumor grading systems, establish optimal cutoff values that have the strongest association with overall survival, and develop a grading system incorporating the histopathologic characteristics that we found to have prognostic significance in patients with lung adenocarcinoma. Methods We studied lung adenocarcinomas from 85 consecutive patients, and evaluated the percentage of solid pattern (as a reflection of tumor architecture), the degree of cytologic atypia, and the mitotic count. Results In univariate analysis, overall survival was associated significantly with sex (P=0.045), age (P=0.0008), tumor status (P<0.0001), node status (P=0.02), solid pattern (P=0.046) and cytologic atypia (P=0.01), but not with mitotic count (P=0.26). Based on optimal cutoff values, we found that a solid pattern ≥ 90% and severe cytologic atypia were the best discriminators of worse outcome. A grading score, computed as the sum of the architecture score and cytologic atypia score (2=well differentiated, 3=moderately differentiated, 4=poorly differentiated), was a significant predictor of overall survival in univariate analysis (median overall survival times 72.4, 39.5, and 8.7 months for well, moderately and poorly differentiated adenocarcinoma, respectively P=0.0001). Moreover, grading was an independent predictor of survival in multivariate analysis (P=0.002). Conclusions We describe a grading system that incorporates the percentage of solid pattern and degree of the cytologic atypia that is an independent predictor of survival in patients with lung adenocarcinoma.
  • No Thumbnail Available
    Publication
    Unique Clinicopathologic Features Characterize ALK-Rearranged Lung Adenocarcinoma in the Western Population
    (American Association for Cancer Research (AACR), 2009-08-15) Rodig, Scott; Mino-Kenudson, Mari; Dacic, Sanja; Yeap, Beow; Shaw, Alice; Barletta, Justine; Stubbs, Hannah; Law, Kenny; Lindeman, Neal; Mark, Eugene; Janne, Pasi; Lynch, Thomas; Johnson, Bruce; Iafrate, Anthony; Chirieac, Lucian
    Purpose The anaplastic large cell kinase gene (ALK) is rearranged in approximately 5% of lung adenocarcinomas within the Asian population. We evaluated the incidence and the characteristics of ALK-rearranged lung adenocarcinomas within the Western population and the optimal diagnostic modality to detect ALK rearrangements in routine clinical practice. Experimental Design We tested 358 lung adenocarcinomas from three institutions for ALK rearrangements by fluorescent in-situ hybridization (FISH) and immunohistochemistry (IHC) with and without tyramide amplification (TA). The clinicopathologic characteristics of tumors with and without ALK rearrangements were compared. Results We identified 20 lung adenocarcinomas (5.6%) with ALK rearrangements within our cohort of Western patients. ALK rearrangement was associated with younger age (P = 0.0002), never smoking (P < 0.0001), advanced clinical stage (P = 0.0001), and a solid histology with signet-ring cells (P < 0.0001). ALK rearrangement was identified by FISH in 95% of cases, IHC with and without TA in 80% and 40% of cases, respectively, but neither FISH nor IHC alone detected all cases with ALK rearrangement on initial screening. None of the ALK-rearranged tumors harbored coexisting EGFR mutations. Conclusions Lung adenocarcinomas with ALK rearrangements are uncommon in the Western population and represent a distinct entity of carcinomas with unique characteristics. For suspected cases dual diagnostic testing, with FISH and IHC, should be considered to accurately identify lung adenocarcinomas with ALK rearrangement.
  • No Thumbnail Available
    Publication
    Characterizing the Cancer Genome in Lung Adenocarcinoma
    (Springer Science and Business Media LLC, 2007-12-06) Weir, Barbara A.; Woo, Michele S.; Getz, Gad; Perner, Sven; Ding, Li; Beroukhim, Rameen; Lin, William; Province, Michael A.; Kraja, Aldi T.; Johnson, Laura A.; Shah, Kinjal; Sato, Mitsuo; Thomas, Roman K.; Barletta, Justine; Borecki, Ingrid B.; Broderick, Stephen; Chang, Andrew C.; Chiang, Derek Y.; Chirieac, Lucian; Cho, Jeonghee; Fujii, Yoshitaka; Gazdar, Adi F.; Giordano, Thomas J.; Greulich, Heidi; Hanna, Megan; Johnson, Bruce; Kris, Mark G.; Lash, Alex; Lin, Ling; Lindeman, Neal; Mardis, Elaine R.; McPherson, John D.; Minna, John D.; Morgan, Margaret B.; Nadel, Mark; Orringer, Mark B.; Osborne, John R.; Ozenberger, Brad; Ramos, Alex H.; Robinson, James; Roth, Jack A.; Rusch, Valerie; Sasaki, Hidefumi; Shepherd, Frances A.; Sougnez, Carrie; Spitz, Margaret R.; Tsao, Ming-Sound; Twomey, David; Verhaak, Roel G. W.; Weinstock, George; Wheeler, David A.; Winckler, Wendy; Yoshizawa, Akihiko; Yu, Soyoung; Zakowski, Maureen F.; Zhang, Qunyuan; Beer, David G.; Wistuba, Ignacio I.; Watson, Mark A.; Garraway, Levi A.; Ladanyi, Marc; Travis, William D.; Pao, William; Rubin, Mark A; Gabriel, Stacey; Gibbs, Richard A.; Varmus, Harold E.; Wilson, Richard K.; Lander, Eric; Meyerson, Matthew
    Somatic alterations in cellular DNA underlie almost all human cancers1. The prospect of targeted therapies2 and the development of high-resolution, genome-wide approaches3–8 are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize copy-number alterations in primary lung adenocarcinomas. By analysis of a large collection of tumors (n = 371) using dense single nucleotide polymorphism arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent large-scale copy-number gain or loss, of which only a handful have been linked to a specific gene. We also identify 31 recurrent focal events, including 24 amplifications and 7 homozygous deletions. Only six of these focal events are currently associated with known mutations in lung carcinomas. The most common event, amplification of chromosome 14q13.3, is found in ~12% of samples. On the basis of genomic and functional analyses, we identify NKX2-1 (NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung adenocarcinomas. More generally, our results indicate that many of the genes that are involved in lung adenocarcinoma remain to be discovered.