scholarly journals EGFR Expression and KRAS and BRAF Mutational Status in Intestinal-Type Sinonasal Adenocarcinoma

2013 ◽  
Vol 14 (3) ◽  
pp. 5170-5181 ◽  
Author(s):  
Vanessa Szablewski ◽  
Jérôme Solassol ◽  
Flora Poizat ◽  
Marion Larrieux ◽  
Louis Crampette ◽  
...  
Keyword(s):  
Intestinal Type ◽  
Egfr Expression ◽  
Mutational Status ◽  
Sinonasal Adenocarcinoma

scholarly journals Recurrent DNA copy number alterations in intestinal-type sinonasal adenocarcinoma

2016 ◽  
Vol 54 (3) ◽  
pp. 278-286
Author(s):  
J. Perez-Escuredo ◽  
A. Lopez-Hernandez ◽  
M. Costales ◽  
F. Lopez ◽  
S.P. Ares ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Copy Number ◽  
Genetic Alterations ◽  
Intestinal Type ◽  
Dust Exposure ◽  
Copy Number Alterations ◽  
A Genome ◽  
Sinonasal Adenocarcinoma ◽  
Gains And Losses ◽  
Microarray Cgh

Background: Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumour related to occupational wood dust exposure. Few studies have described recurrent genetic changes on a genome-wide scale. The aim of this study was to obtain a high resolution map of recurrent genetic alterations in ITAC. Material and methods: Copy number alterations were evaluated by microarray CGH and MLPA in 37 primary tumours. The results were correlated with pathological characteristics and clinical outcome. Results: Microarray CGH identified the following recurrent aberrations, in descending order: gains at 5p15 (22 cases, 60%), 8q24 (21 cases, 57%), 20q13 (20 cases, 54%), 20q11, and 8q21 (19 cases, 51%), 20p13, and 7p11 (16 cases, 43%), and losses at 5q11-qter, 8p12-pter, and 18q12-23 (15 cases, 40%), and 17p13, and 19p13 (13 cases, 35%). MLPA analysis confirmed this global pattern of gains and losses. Chromosomal loss at 4q32-ter and gains at 1q22, 6p22 and 3q29, as well as deletion of TIMP2 and CRK correlated with unfavourable clinical outcome. Conclusion: ITACs have a unique pattern of chromosomal abnormalities. The four different histological subtypes of ITAC appeared genetically similar. Four chromosomal gains and losses and two specific genes showed prognostic value and may be involved in tumour progression.

P18 Clinical management of intestinal-type sinonasal adenocarcinoma: A monoinstitutional experience of 165 cases

Oral Oncology ◽  
2015 ◽  
Vol 51 (5) ◽  
pp. e48
Author(s):  
M. Costales ◽  
F. López ◽  
B. Vivanco ◽  
C. García-Inclán ◽  
A. López-Hernández ◽  
...  
Keyword(s):  
Clinical Management ◽  
Intestinal Type ◽  
Sinonasal Adenocarcinoma

Cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) against tumor cell lines characterized for EGFR expression and K-ras mutation

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14583-e14583 ◽  
Author(s):  
J. Barriere ◽  
J. Fischel ◽  
P. Formento ◽  
N. Renée ◽  
M. Francoual ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Mononuclear Cells ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Human Cancer ◽  
Tumor Cell Lines ◽  
Ras Mutation ◽  
Egfr Expression ◽  
Mutational Status

e14583 Background: Mutated K-ras protein is a strong predictive factor of cetuximab resistance, bypassing the classical direct inhibitory effect on epidermal growth factor receptor (EGFR) signaling. However, cetuximab is also able to mediate ADCC, which may be part of the clinical response. The aim of this ex-vivo study was to quantify cetuximab-mediated ADCC on various human cancer cell lines characterized for EGFR-expression and K-ras mutation. Methods: Two K-ras mutated cell lines over-expressing EGFR and resistant to anti-EGFR tyrosine kinase inhibitor were tested (Capan-1 and Capan-2, pancreatic), along with 2 K-ras wild-type cell lines over- expressing EGFR (CAL166, head and neck; A431, epidermoid carcinoma) and an EGFR-negative cell line (OCM1, uveal melanoma). The tested monoclonal antibodies (mAbs) were: cetuximab (Merck, anti-EGFR IgG1 mAb), panitumumab (Amgen, anti-EGFR IgG2 mAb), and as a negative control, rituximab (Roche, IgG1 anti-CD20 mAb). ADCC (51Cr release assay) was performed using freshly- isolated peripheral blood mononuclear cells from a healthy donor. Results were expressed as % of potentially maximum 51Cr release. Results: Cetuximab mediates ADCC against EGFR-over-expressing cell lines CAL166 (38.4 ± 3.1 %), A431 (13.5 ± 1.7 %), Capan-1 (31.2 ± 0.8 %) and Capan-2 (27.8 ± 8.6 %) irrespective of the K-ras mutational status, but not against EGFR-negative OCM-1 (6.2 ± 1 %). Conversely, unlike IgG1 cetuximab, the anti-EGFR IgG2 panitumumab and the irrelevant antibody rituximab were both unable to induce significant ADCC (< 10 % on all tested cell lines). Conclusions: Cetuximab-mediated ADCC is independent of the K-ras mutational status of the tumor cell lines. Present data suggest that cetuximab may remain of clinical interest in K-ras-mutated patients. Immunostimulation, as well as new generation anti-EGFR mAbs with improved ability to induce ADCC, may be promising in the management of K-ras-mutated patients. No significant financial relationships to disclose.

Prediction of TP53 Status for Primary Cisplatin, Fluorouracil, and Leucovorin Chemotherapy in Ethmoid Sinus Intestinal-Type Adenocarcinoma

2004 ◽  
Vol 22 (24) ◽  
pp. 4901-4906 ◽  
Author(s):  
L. Licitra ◽  
S. Suardi ◽  
P. Bossi ◽  
L.D. Locati ◽  
L. Mariani ◽  
...  
Keyword(s):  
Complete Remission ◽  
P53 Protein ◽  
Disease Free Survival ◽  
Intestinal Type ◽  
Primary Chemotherapy ◽  
Mutational Status ◽  
Intestinal Type Adenocarcinoma ◽  
Pathologic Complete Remission ◽  
Tp53 Status ◽  
Disease Free

Purpose To assess the role of TP53 status in predicting pathologic complete remission after primary chemotherapy in patients with ethmoidal intestinal-type adenocarcinoma (ITAC). Patients and Methods Thirty patients with ethmoidal ITAC enrolled onto a phase II study received chemotherapy with cisplatin, fluorouracil, and leucovorin (PFL) followed by surgery and radiation. On surgical specimens, absence of viable tumor cells was defined as pathologic complete remission (pCR). TP53 status/p53 function, analyzed on pretreatment biopsies, were retrospectively correlated with pathologic results and patient outcome. Results Twelve patients achieved a pCR; 18 patients did not (overall response rate, 40%). In patients with wild-type (wt) TP53 or functional p53 protein, the pCRs were 83% and 80%, respectively; in patients with mutated TP53 or impaired p53 protein, pCRs were 11% and 0%, respectively (P ≤ .0001). At a median 55-month follow-up, all pCR patients were disease-free; 44% of nonresponding patients experienced relapse (P = .0061). Conclusion The results indicate the existence of two genetic ITAC subgroups, defined by differences in TP53 mutational status or protein functionality, that strongly influence pathologic response to primary chemotherapy and, ultimately, prognosis. PFL seems to be highly effective in terms of pCR and disease-free survival in the presence of a wt or a still-efficient p53 protein, even when encoded by a mutated TP53 gene (eg, early-stop codon mutation), but ineffective in ITACs carrying a disabled p53 protein. Whether this model is extensible to other head and neck cancers needs appropriate investigation.

scholarly journals Establishment and genetic characterization of an immortal tumor cell line derived from intestinal-type sinonasal adenocarcinoma

2011 ◽  
Vol 34 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Jhudit Pérez-Escuredo ◽  
Jorge García Martínez ◽  
Cristina García-Inclán ◽  
Blanca Vivanco ◽  
María Costales ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Genetic Characterization ◽  
Tumor Cell Line ◽  
Intestinal Type ◽  
Sinonasal Adenocarcinoma

scholarly journals A case of chemotherapy-resistant intestinal-type sinonasal adenocarcinoma treated by gamma knife radiosurgery

2017 ◽  
Vol 10 ◽  
pp. 135-137
Author(s):  
Andres M. Alvarez-Pinzon ◽  
Jose E. Valerio ◽  
Beatriz E. Amendola ◽  
Devi Lakhlani ◽  
Alan A. Stein ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
Intestinal Type ◽  
Sinonasal Adenocarcinoma

Phase II Study of Erlotinib in Recurrent or Metastatic Endometrial Cancer: NCIC IND-148

2008 ◽  
Vol 26 (26) ◽  
pp. 4319-4325 ◽  
Author(s):  
Amit M. Oza ◽  
Elizabeth A. Eisenhauer ◽  
Laurie Elit ◽  
Jean-Claude Cutz ◽  
Akira Sakurada ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Gene Amplification ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Egfr Mutations ◽  
Severe Toxicity ◽  
Egfr Expression ◽  
Mutational Status

Purpose Epidermal growth factor receptor (EGFR) overexpression is common in endometrial cancers and may have a major role in tumor growth and progression. Erlotinib is an orally active, selective inhibitor of EGFR tyrosine kinase activity. Patients and Methods A multinomial design two-stage phase II study was performed to evaluate single-agent activity of erlotinib in women with advanced endometrial cancer with recurrent or metastatic disease who were chemotherapy naïve and had received up to one line of prior hormonal therapy. Erlotinib was administered at daily dose of 150 mg. Archival tumor tissue was analyzed for EGFR expression by immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH). Mutational status of EGFR was determined in responders. Results Thirty-two of 34 entered patients are assessable for response. Treatment was well tolerated and severe toxicity infrequent, with the only grade 4 toxicity being an elevation of transaminases (AST). There were four confirmed partial responses (PRs; 12.5%; 95% CI, 3.5% to 29%) lasting 2 to 36 months. Fifteen patients had stable disease (SD), with median duration of 3.7 months (range, 2 to 12 months). EGFR expression was analyzed in thirty patients; 19 were positive, nine were negative, and two were not assessable. Of the 19 patients who were EGFR positive, three had PR (16%), seven SD, and eight progressive disease, and one was not assessable. No mutations were identified in responders. FISH showed no correlation of response with gene amplification. Conclusion Erlotinib is well tolerated with an overall objective response rate of 12.5%. Molecular analysis did not identify EGFR mutations in responders or correlation of response with gene amplification.

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