TY - JOUR
T1 - WWOX expression in different histologic types and subtypes of non-small cell lung cancer
AU - Donati, Valentina
AU - Fontanini, Gabriella
AU - Dell'Omodarme, Matteo
AU - Prati, Maria Cristina
AU - Nuti, Simona
AU - Lucchi, Marco
AU - Mussi, Alfredo
AU - Fabbri, Muller
AU - Basolo, Fulvio
AU - Croce, Carlo Maria
AU - Aqeilan, Rami Ishaq
PY - 2007/2/1
Y1 - 2007/2/1
N2 - Purpose: Non -small cell lung cancer (NSCLC) has heterogeneous histopathologic classification and clinical behavior and very low survival rate. WWOX (WW domain-containing oxidoreductase) is a tumor suppressor gene, and its expression is altered in several cancers. The purpose of this study is to better define the role of WWOX in NSCLC tumorigenesis and progression by determining its pathogenetic and prognostic significance. Experimental Design: WWOX protein expression was evaluated by immunohistochemistry in 170 patients with NSCLC (101 squamous cell carcinomas, 66 adenocarcinomas, 3 large cell carcinomas) and was correlated with histopathologic (histotype, subtype, grade, tumor-node- metastasis, stage, index of cell proliferation Ki67/MIB1) and clinical (age, gender, local recurrences, distant metastases, overall survival, and disease-free survival) characteristics. Results: WWOX expression was absent/reduced in 84.9% of NSCLCs, whereas it was normal in 80.5% of adjacent normal lung tissues. WWOX expression was strongly associated with tumor histology (P = 1.1·10-5) and histologic grade (P = 0.0081): the percentage of cases with absent/strongly reduced WWOX expression was higher in squamous cell carcinomas and in poorly differentiated tumors. Regarding adenocarcinoma, bronchioloalveolar pattern showed normal WWOX expression in 62.5% of the cases, whereas in solid and acinar patterns, a prevalence of cases with absent/very low WWOX expression was observed (79.2% and 50%, respectively). Finally, weak WWOX staining intensity was related to the high index of cell proliferation (P = 0.0012). Conclusions: Our results suggest that the loss of WWOX expression plays different roles in tumorigenesis of distinct histotypes and subtypes of NSCLC and is related to high aggressiveness (G3; high proliferating activity) of tumors.
AB - Purpose: Non -small cell lung cancer (NSCLC) has heterogeneous histopathologic classification and clinical behavior and very low survival rate. WWOX (WW domain-containing oxidoreductase) is a tumor suppressor gene, and its expression is altered in several cancers. The purpose of this study is to better define the role of WWOX in NSCLC tumorigenesis and progression by determining its pathogenetic and prognostic significance. Experimental Design: WWOX protein expression was evaluated by immunohistochemistry in 170 patients with NSCLC (101 squamous cell carcinomas, 66 adenocarcinomas, 3 large cell carcinomas) and was correlated with histopathologic (histotype, subtype, grade, tumor-node- metastasis, stage, index of cell proliferation Ki67/MIB1) and clinical (age, gender, local recurrences, distant metastases, overall survival, and disease-free survival) characteristics. Results: WWOX expression was absent/reduced in 84.9% of NSCLCs, whereas it was normal in 80.5% of adjacent normal lung tissues. WWOX expression was strongly associated with tumor histology (P = 1.1·10-5) and histologic grade (P = 0.0081): the percentage of cases with absent/strongly reduced WWOX expression was higher in squamous cell carcinomas and in poorly differentiated tumors. Regarding adenocarcinoma, bronchioloalveolar pattern showed normal WWOX expression in 62.5% of the cases, whereas in solid and acinar patterns, a prevalence of cases with absent/very low WWOX expression was observed (79.2% and 50%, respectively). Finally, weak WWOX staining intensity was related to the high index of cell proliferation (P = 0.0012). Conclusions: Our results suggest that the loss of WWOX expression plays different roles in tumorigenesis of distinct histotypes and subtypes of NSCLC and is related to high aggressiveness (G3; high proliferating activity) of tumors.
UR - http://www.scopus.com/inward/record.url?scp=33847375923&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-06-2016
DO - 10.1158/1078-0432.CCR-06-2016
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C2 - 17289881
AN - SCOPUS:33847375923
SN - 1078-0432
VL - 13
SP - 884
EP - 891
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 3
ER -