Prognostic Factors in Non-small Cell Lung Cancer

Brundage, Michael; Davies, Diane; Mackillop, William J.

doi:10.1378/chest.122.3.1037

Cited by 510 publications

(378 citation statements)

References 223 publications

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“…19 Our selected group of patients was validated by integrating newly studied markers with significant factors identified in earlier studies, such as tumor lymph node metastasis (TNM) staging system parameters. 16,20 The stage of disease and the lymph node involvement were correlated with patient survival in both univariate and multivariate statistical analyses, a fact that supports the accurate representation of our TMA samples. Lee et al 9 studied 115 cases of NSCLC (3 cm or less in size) for E-cad and catenins expressions using IHC.…”

Section: Study Of Altered E-cad and Egfr Expressions G Deeb Et Alsupporting

confidence: 72%

Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry

et al. 2004

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E-cadherin (E-cad) and epidermal growth factor receptor (EGFR) are important cell adhesion and signaling pathway mediators. This study aimed to assess their expression in lung adenocarcinoma (AdC) and squamous cell carcinoma (SCC) and their association with clinicopathologic variables. In all, 130 resectable lung cancers (stages I-IIIA) were studied using a high-density tissue microarray. Two to three cores from each case were arrayed into three blocks using a Beecher system. Immunohistochemistry was performed using an avidinbiotin complex method and monoclonal antibodies against E-cad and EGFR. Unequivocal membrane staining in 410% of tumor cells was considered as a positive expression of E-cad and EGFR. Markers expression and coexpression were analyzed against clinicopathologic variables (age, gender, smoking status, performance status, weight loss, histology, grade, stage, and lymph node involvement) and patient survival. There were 118, 126, and 115 cases that were fully assessable for E-cad, EGFR, and both markers, respectively. For E-cad, 65 cases (55%) were positive ( þ ), 53 (45%) were negative (À); 23 cases of the negative group had only cytoplasmic staining. For EGRF, 43 cases (34%) were ( þ ), and 83 (66%) were (À). There was no significant association between E-cad or EGFR, and any of the clinicopathologic variables except for an association between EGFR( þ ) and SCC histologic type. Both negative and cytoplasmic staining of E-cad correlated with shorter patient survival with P ¼ 0.008 and 0.002, respectively. EGFR expression did not correlate with patient survival; however, patients with E-cad(À)/EGFR( þ ) phenotype had poorer survival than those with E-cad( þ )/EGFR(À) (P ¼ 0.026). Our study suggests that lung AdC and SCC may be stratified based on expression of E-cad and EGFR with the E-cad(À)/EGFR( þ ) expression having a worse disease outcome. Moreover, the cytoplasmic expression of E-cad may represent an altered localization of this protein in association with tumorigenicity.

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Section: Study Of Altered E-cad and Egfr Expressions G Deeb Et Alsupporting

confidence: 72%

Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry

et al. 2004

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“…Therefore, a substantial amount of research on the biology of NSCLC has focused on evaluating the potential of new molecular markers present in tumour cells to serve as prognostic factors or possible targets for therapy. Although a variety of molecular markers have been implicated in the prognosis of NSCLC, conflicting results were widely reported in the literature (Brundage et al, 2002). Thus, further investigations are required to develop appropriate markers (PCIo10%); (D) high-level expression of ADC (PCI ¼ 80%); magnification 1 Â 10; detection of Rad51 protein by immunohistochemistry using the monoclonal anti-Rad51 antibody 1G8 ; counterstaining with Hemalum; red arrows mark tumour cells expressing high levels of Rad51.…”

Section: Discussionmentioning

confidence: 99%

High-level expression of Rad51 is an independent prognostic marker of survival in non-small-cell lung cancer patients

et al. 2005

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High-level expression of Rad51, a key factor in homologous recombination, has been observed in a variety of human malignancies. This study was aimed to evaluate Rad51 expression to serve as prognostic marker in non-small-cell lung cancer (NSCLC). A total of 383 non-small-cell lung tumours were analysed immunohistochemically on NSCLC tissue microarrays. High-level Rad51 expression was observed in 29.4% (100 out of 340) of cases. Patients whose tumours displayed high-level Rad51 expression showed a significantly shorter median survival time of 19 vs 68 months (Po0.0001, log-rank test). Similarly T status, N status, M status, clinical stage and histological tumour grade were significant prognostic markers in univariate Cox survival analysis. Importantly, Rad51 expression (Po0.0001) together with tumour differentiation (Po0.009), clinical stage (P ¼ 0.004) and N status (P ¼ 0.0001) proved to be independent prognostic parameters in multivariate analysis. Rad51 expression predicted the outcome of squamous cell cancer as well as adenocarcinoma of the lung. Our results suggest that Rad51 expression provides additional prognostic information for surgically treated NSCLC patients. We hypothesise that the decreased survival of NSCLC patients with high-level expression of Rad51 is related to an enhanced propensity of tumour cells for survival, antiapoptosis and chemo-/radioresistance.

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“…To improve the prognosis of patients, clinical markers that may predict the prognosis and response to the specific therapy should be established. Tumour staging and performance status have been consistently shown to be the most powerful prognostic tool for survival rates of NSCLC patients (Brundage et al, 2002). The prognostic factors such as 'N' factor, tumour size, sex, and vessel invasion have been shown to determine overall outcome in patients with surgically resected NSCLC (Brundage et al, 2002).…”

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confidence: 99%

Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I–III nonsmall cell lung cancer

et al. 2008

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The clinical significance of L-type amino acid transporter 1 (LAT1) expression remains unclear, whereas many experimental studies have demonstrated that LAT1 is associated with the proliferation of cancer cells. The purpose of this study was to evaluate the prognostic value of LAT1 in patients with nonsmall cell lung cancer (NSCLC). A total of 321 consecutive patients with completely resected pathologic stage I -III NSCLC were retrospectively reviewed. Expression of LAT1 and proliferative activity, as determined by the Ki-67 labelling index, was also evaluated immunohistochemically and correlated with the prognosis of patients who underwent complete resection of the tumour. Expression of LAT1 was positive in 163 patients (51%) (29% of adenocaricnoma (58 of 200 patients), 91% of squamous cell carcinoma (91 of 100 patients), and 67% of large cell carcinoma (14 of 21 patients)). The 5-year survival rate of LAT1-positive patients (51.8%) was significantly worse than that of LAT1-negative patients (87.8%; Po0.001). L-type amino acid transporter 1 expression was significantly associated with lymph node metastasis and disease stage. Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis. There was a significant correlation between LAT1 expression and Ki-67 labelling index. LAT1 expression is a promising pathological factor to predict the prognosis in patients with resectable stage I -III NSCLC.

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Prognostic Factors in Non-small Cell Lung Cancer

Cited by 510 publications

References 223 publications

Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry

Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry

High-level expression of Rad51 is an independent prognostic marker of survival in non-small-cell lung cancer patients

Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I–III nonsmall cell lung cancer

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