Patricia Pintor Dos Reis

Publications (6)37.85 Total impact

• Article: Claudin 1 overexpression increases invasion and is associated with aggressive histological features in oral squamous cell carcinoma.

  Patricia Pintor Dos Reis, Rikki R Bharadwaj, Jerry Machado, Christina Macmillan, Melania Pintilie, Mahadeo A Sukhai, Bayardo Perez-Ordonez, Patrick Gullane, Jonathan Irish, Suzanne Kamel-Reid
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  ABSTRACT: The authors have previously shown that overexpression of claudin 1 (CLDN1) is associated with advanced disease stage in oral squamous cell carcinomas (OSCCs). Their goal was to examine CLDN1 expression in a large series of primary OSCCs and to further investigate whether CLDN1 overexpression plays a role in invasion in OSCC. CLDN1 gene expression levels were determined by quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR) in 100 primary OSCCs. CLDN1 protein expression was examined by immunohistochemistry in 70 of 100 OSCCs. E-Cadherin protein levels were also assessed in 58 OSCCs. The authors performed a transwell Matrigel invasion assay for assessment of the invasive potential of CLDN1 overexpressing oral carcinoma cells. Western blotting and QRT-PCR were used to assess CLDN1 expression in transfected cells and controls. CLDN1 mRNA was increased (median = 18.5) in 79 of 100 OSCCs, compared with normal oral mucosa (expression = 1.0). CLDN1 overexpression was associated with angiolymphatic (P = .037) and perineural invasion (P = .051). CLDN1 was highly expressed in 48 of 70 (68%) OSCCs. E-Cadherin was lost or underexpressed in 49 of 58 (84%) OSCCs. The invasion assay showed that cells overexpressing CLDN1 have increased invasive potential, whereas small interfering RNA-mediated depletion of CLDN1 decreased the invasive potential of cells. CLDN1 overexpression is associated with angiolymphatic and perineural invasion, consistent with aggressive tumor behavior. Overexpression of CLDN1 protein is associated with increased invasiveness of oral carcinoma cells.
  Cancer 12/2008; 113(11):3169-80. · 4.77 Impact Factor
• Article: Predictive and pharmacodynamic biomarker studies in tumor and skin tissue samples of patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with erlotinib.

  Mark Agulnik, Gilda da Cunha Santos, David Hedley, Trudey Nicklee, Patricia Pintor Dos Reis, James Ho, Gregory R Pond, Heidi Chen, Shuo Chen, Yu Shyr, Eric Winquist, Denis Soulieres, Eric X Chen, Jeremy A Squire, Paula Marrano, Suzanne Kamel-Reid, Janet Dancey, Lillian L Siu, Ming S Tsao
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  ABSTRACT: PURPOSE Pharmacodynamic tissue studies were conducted on a phase I/II trial of erlotinib and cisplatin in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Levels of epidermal growth factor receptor (EGFR), downstream signaling components, and markers of angiogenesis and apoptosis were evaluated to determine the relationship between correlative end points and clinical outcomes. PATIENTS AND METHODS Pretreatment and during-treatment tumor and skin biopsies, and archival tumor specimens were evaluated for EGFR, phosphorylated (p) -EGFR, extracellular signal-regulated kinase (ERK), p-ERK, Akt, p-Akt, Ki67, p27, p-nuclear factor kappa B (NFkappaB), p-signal transducer and activator of transcription 3 (STAT3), and EGFR gene copy number. Results On 37 archival samples, response to therapy was evident in two of four (50%) patients with high EGFR gene copy number tumors and in four of 27 (15%) patients with low gene copy number tumors. On nine paired tumor biopsies, elevated pretreatment levels of p27 and p-STAT3 predicted for prolonged time to progression (TTP) and overall survival (OS; P < or = .03). With treatment, a decrease in p-EGFR, p-NFkappaB, and p27 correlated with increased TTP, OS, or both TTP and OS, respectively (P < or = .04). Multidimensional scaling (MDS) models revealed clustering profiles of tumor markers by immunofluorescence could predict response. On 32 paired skin biopsies, suppression of p-EGFR with therapy correlated with increased OS (P = .045). CONCLUSION High EGFR gene copy in tumor specimens may predict which patients have an increased likelihood of response to erlotinib, and decreased p-EGFR level in skin biopsies during therapy may represent a potential surrogate marker for improved clinical outcome. MDS represents a novel way to evaluate the relationships between molecular markers and clinical outcome. Additional biomarker studies with larger sample sizes are required to elucidate HNSCC patients who may benefit from this targeted therapy.
  Journal of Clinical Oncology 06/2007; 25(16):2184-90. · 18.37 Impact Factor
• Article: Young patients with oral squamous cell carcinoma: study of the involvement of GSTP1 and deregulation of the Fanconi anemia genes.

  Steve Tremblay, Patricia Pintor Dos Reis, Grace Bradley, Natalie Naranjo Galloni, Bayardo Perez-Ordonez, Jeremy Freeman, Dale Brown, Ralph Gilbert, Patrick Gullane, Jonathan Irish, Suzanne Kamel-Reid
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  ABSTRACT: To investigate whether oral squamous cell carcinomas (OSCCs) from young (</=40 years) and older (>/=60 years) patients have differential expression levels of GSTP1, FANCA, FANCC, FANCD2, and FANCG. Quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemical analysis were used to assess gene and protein expression, respectively. This study was performed in a research institute within a hospital setting. Our study group consisted of 104 patients (42 young and 62 older). We collected RNA from 32 OSCC samples (10 young and 22 older patients) for gene expression analysis. Seventy-seven OSCC samples (37 from young and 40 from older patients) were used for protein expression analysis. Five patients were studied in both analyses. Lower expression of GSTP1 (P = .04) and FANCA (P = .01) was observed in the tumors of young compared with older patients. We also detected lower expression of GSTP1 in the tumors of young patients compared with their nondysplastic mucosa (P = .01). FANCA was underexpressed in nondysplastic mucosa of young compared with older patients (P = .01). GSTP1 protein showed negative or low expression in 41% (n = 15 of 37) of young vs 5% (n = 2 of 40) of older patient tumors (P = .001). FANCG protein expression was absent or low in 81% (n = 30 of 37) of young compared with 36% (n = 15 of 40) of older patient tumors (P<.001). Differences in expression levels of GSTP1, FANCA, and FANCG in OSCC of young and older patients suggest that different mechanisms may be involved in tumor development through defective carcinogen metabolism and/or DNA repair capabilities. GSTP1 plays a key role in detoxification; therefore, underexpression of this gene in tumors of young patients may cause deficient detoxification that could lead to an increased susceptibility to the development of oral carcinoma.
  Archives of Otolaryngology - Head and Neck Surgery 10/2006; 132(9):958-66. · 1.63 Impact Factor
• Article: Molecular characterization of salivary gland malignancy using the Smgb-Tag transgenic mouse model.

  Antti A Mäkitie, Patricia Pintor Dos Reis, Shilpi Arora, Christina Macmillan, Giles C Warner, Mahadeo Sukhai, Irving Dardick, Bayardo Perez-Ordonez, Richard Wells, Dale Brown, Ralph Gilbert, Jeremy Freeman, Patrick Gullane, Jonathan Irish, Suzanne Kamel-Reid
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  ABSTRACT: The molecular mechanisms underlying salivary gland tumorigenesis remain unclear. In order to identify genetic changes that occur during the development of invasive adenocarcinoma from normal salivary gland, we used the Smgb-Tag transgenic mouse model. This transgene induces the progressive development of dysplasia to invasive adenocarcinoma in the submandibular salivary gland. Gene expression patterns from 20 submandibular glands (two normal, nine dysplasia and nine adenocarcinoma samples) were assessed using a mouse 15 K cDNA array. Unsupervised hierarchical clustering was used to group gene expression based on 157 differentially expressed genes distinguishing between dysplasias and adenocarcinomas. Further analysis identified 25 significantly overexpressed and 28 underexpressed cDNA sequences in adenocarcinoma as compared to dysplasia. Differential expression of five genes (Lcn2, Ptn, Cd24a, Mapk6 and Rnps1) was validated by quantitative real-time RT-PCR in a total of 48 mouse salivary gland tissues (seven histologically normal, 13 dysplasias and 28 adenocarcinomas), including the 20 samples analyzed by cDNA arrays. Immunohistochemical analysis was used to validate the expression of Ptn and Cd24a at the protein level in a subset of 16 mouse salivary glands (four normal, five dysplasia and seven adenocarcinoma samples), as well as in 23 human submandibular gland tumors (16 pleomorphic adenomas, three adenoid cystic carcinomas, one acinic cell carcinoma, one adenocarcinoma NOS, one myoepithelial and one mucoepidermoid carcinoma). We thus demonstrated that the Smgb-Tag transgenic mouse model is a useful tool for the identification of genes that are deregulated in salivary gland adenocarcinomas. Our data suggest that Ptn and Cd24a may be genetic markers associated with salivary gland tumorigenesis and/or progression.
  Laboratory Investigation 09/2005; 85(8):947-61. · 3.64 Impact Factor
• Article: Classic and molecular cytogenetic analyses reveal chromosomal gains and losses correlated with survival in head and neck cancer patients.

  Nádia Aparecida Bérgamo, Luciana Caricati da Silva Veiga, Patricia Pintor dos Reis, Inês Nobuko Nishimoto, José Magrin, Luiz Paulo Kowalski, Jeremy A Squire, Sílvia Regina Rogatto
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  ABSTRACT: Genetic biomarkers of head and neck tumors could be useful for distinguishing among patients with similar clinical and histopathologic characteristics but having differential probabilities of survival. The purpose of this study was to investigate chromosomal alterations in head and neck carcinomas and to correlate the results with clinical and epidemiologic variables. Cytogenetic analysis of short-term cultures from 64 primary untreated head and neck squamous cell carcinomas was used to determine the overall pattern of chromosome aberrations. A representative subset of tumors was analyzed in detail by spectral karyotyping and/or confirmatory fluorescence in situ hybridization analysis. Recurrent losses of chromosomes Y (26 cases) and 19 (14 cases), and gains of chromosomes 22 (23 cases), 8 and 20 (11 cases each) were observed. The most frequent structural aberration was del(22)(q13.1) followed by rearrangements involving 6q and 12p. The presence of specific cytogenetic aberrations was found to correlate significantly with an unfavorable outcome. There was a significant association between survival and gains in chromosomes 10 (P = 0.008) and 20 (P = 0.002) and losses of chromosomes 15 (P = 0.005) and 22 (P = 0.021). Univariate analysis indicated that acquisition of monosomy 17 was a significant (P = 0.0012) factor for patients with a previous family history of cancer. The significant associations found in this study emphasize that alterations of distinct regions of the genome may be genetic biomarkers for a poor prognosis. Losses of chromosomes 17 and 22 can be associated with a family history of cancer.
  Clinical Cancer Research 02/2005; 11(2 Pt 1):621-31. · 7.74 Impact Factor
• Article: Distinct regions of loss of heterozygosity on 22q in different sites of head and neck squamous cell carcinomas.

  Patricia Pintor dos Reis, Regina Célia Poli-Frederico, Rodrigo Mattos dos Santos, Ines Nobuko Nishimoto, Luiz Paulo Kowalski, Silvia Regina Rogatto
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  ABSTRACT: Frequent loss of heterozygosity (LOH) has been reported in many types of cancer, including head and neck carcinomas. Somatic deletions involving specific chromosomal regions are strongly associated with inactivation of the allele of a tumor suppressor gene located within the deleted region. In most studies concerning LOH in head and neck squamous cell carcinomas (HNSCC) the different anatomical sites are not distinguished. The behavior of tumors arising at various sites differs significantly, however, suggesting different intrinsic tumor properties. In this study we compared the LOH on 22q and its relationship to clinicopathological parameters at the three major sites of HNSCC: oral cavity, larynx and pharynx. LOH and microsatellite instability (MSI) were studied using seven polymorphic microsatellite markers mapped to the 22q11-q13.3 region in 37 oral, 32 laryngeal, and 31 pharyngeal carcinomas. Two separate regions of LOH were identified in the laryngeal (22q11.2-12.1) and oral cavity (22q13.1-13.31) tumors. When the different anatomical sites were compared, a statistically significant difference was found between the presence of LOH at D22S421 (p<0.001), D22S315 (p=0.014) and D22S929 (p=0.026) in the laryngeal tumors. These data suggest that distinct regions on 22q are involved in LOH in oral cavity and laryngeal tumorigenesis, but do not support a similar association between the development of pharyngeal tumors and genes located on 22q. These findings implicate the presence of different tumor suppressor genes mapping to distinct regions on chromosome 22q in oral and laryngeal carcinomas.
  Medical science monitor: international medical journal of experimental and clinical research 03/2002; 8(3):BR89-94. · 1.70 Impact Factor