Tsuchiya T, Akamine S, Muraoka M, et al. Stage IA non-small cell lung cancer: vessel invasion is a poor prognostic factor and a new target of adjuvant chemotherapy

Department of Chest Surgery, Oita Prefectural Hospital, 476 Bunyou, Oita-city, Oita 870-8511, and Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Lung Cancer (Impact Factor: 3.96). 06/2007; 56(3):341-8. DOI: 10.1016/j.lungcan.2007.01.019
Source: PubMed


This study reports the efficacy of adjuvant chemotherapy in stage IA non-small cell lung cancer (NSCLC) with vessel invasion (Vi). We sub-divided 322 patients with surgically resected pathological stage IA NSCLC into two groups according to Vi [non-Vi (n=237) and Vi (n=85)]. Both groups were compared with regard to age, gender, performance status, smoking habits, serum carcinoembryonic antigen level, extent of surgery, tumour size, histopathology, recurrence sites, and survival. The overall 5-year survival rates of non-Vi and Vi groups were 89.6% and 71.8% (P<0.001), respectively. Distant metastasis was observed more frequently in the Vi group (P<0.001, risk ratio: 9.06). Univariate and multivariable analyses identified poor performance status, squamous cell carcinoma, tumour size>or=15 mm and Vi as poor prognostic factors (P<0.05). The overall 5-year survival rate of stage IA Vi group nearly overlapped with that of patients with stage IB NSCLC. Retrospectively, oral uracil-tegafur chemotherapy increased the overall 5-year survival rate of stage IA Vi group by more than 25% (P=0.036). In conclusion, vessel invasion is a poor prognostic factor in patients with stage IA NSCLC. Prognosis of patients with Vi-stage IA NSCLC is similar to that of patients with stage IB NSCLC and is improved significantly by postoperative oral uracil-tegafur chemotherapy. Our preliminary study suggests that stage IA Vi group benefits from adjuvant chemotherapy.

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    • "Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancerrelated mortality worldwide, with over 1 million deaths each year [1], and although significant advances have been made with therapies, the 5-year survival rate of lung cancer is below 20% [2]. The best chance of achieving long-term survival is in complete surgical resection; however, even in resected stage IA patients, 30% succumb from their disease within 5 years [3]. Previous studies have reported several factors associated with poor prognosis in non-small cell lung cancer (NSCLC) patients after surgical resection, such as tumor size, preoperative serum CEA level, visceral pleural invasion, vascular vessel invasion, and histological grade [4-8]. "
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    ABSTRACT: Here, we show that overexpression of fer tyrosine kinase (FER), a non-receptor tyrosine kinase, predicts poor postoperative outcome and might be involved in cancer-cell survival in non-small cell lung cancer (NSCLC). Systematic screening using in silico analyses and quantitative RT-PCR revealed that FER was overexpressed in about 10% of NSCLC patients. Evaluation of FER expression using immunohistochemistry (IHC) on tissue microarrays was consistent with the mRNA level detected using quantitative RT-PCR. In analyses of 135 NSCLC patients who had undergone potential curative resection, we found that FER overexpression detected using IHC had no association with clinicopathological features such as age, sex, smoking history, histological type, disease stage, T factor, N factor, adjuvant chemotherapy history, or EGFR mutation, but was correlated with poor postoperative survival periods. A multivariate Cox regression analysis showed that this prognostic impact was independent of other clinicopathological features. In functional analyses of FER in vitro, FER exhibited a transforming activity, suggesting that it possesses oncogenic functions. We also found that human lung cancer NCI-H661 cells, which exhibited FER-outlier expression, were led to apoptosis by the knockdown of FER using RNA interference. FER overexpression might serve as a prognostic biomarker and be involved in cancer-cell survival in NSCLC.
    International journal of clinical and experimental pathology 04/2013; 6(4):598-612. · 1.89 Impact Factor
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    • "Lung cancer is the leading cause of cancer-related deaths, worldwide, in both men and women, with over one million cases diagnosed yearly.1 Despite progress in the multimodality treatment of lung cancer, prognosis is still poor with 10 to 15% 5-year survival rates. Even in patients with resected stage IA tumors, the survival rate still ranges from 66 to 85%.2 Non-small cell lung cancer (NSCLC) accounts for >80% of all lung cancers. However, only a minority of NSCLC patients would be eligible for radical treatment as a curative care. "
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    ABSTRACT: Ezrin, a member of the ezrin-radixin-moesin family, is implicated in tumor progression, metastatic dissemination, and adverse outcomes, in several cancer types. In this study, we explored the clinicopathological significance of ezrin expression in non-small cell lung carcinomas (NSCLCs). Immunohistochemical analysis of tissue microarray with 112 surgically resected NSCLC specimens, was performed to examine the ezrin expression. We also correlated ezrin expression with other clinicopathological features and prognosis. The ezrin-positive group revealed significantly higher correlation with pleural invasion (p=0.016) and pathologic stage (p=0.050). Univariate survival analysis showed that ezrin-positive group had a significantly shorter cancer-specific survival than ezrin-negative group (p=0.016). Meanwhile, female (p=0.030), no pleural invasion (p=0.023), no lymphatic invasion (p=0.026), and early pathologic stage (p=0.008) significantly correlated with longer survival. Multivariate survival analysis showed that variables such as ezrin positivity (p=0.032), female (p=0.035), and early pathologic stage (p=0.001) were independent prognostic factors for NSCLC. Ezrin might be a molecular marker to predict poor prognosis of NSCLC.
    10/2012; 46(5):470-7. DOI:10.4132/KoreanJPathol.2012.46.5.470
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    • "Here we show that angioinvasion is a poor prognostic factor in early stage NSCLC as was reported in several previous studies [6] [7] [8]. "
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    ABSTRACT: A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC. The aim of this study was to verify the above study by examining the angioinvasion and mTOR expression profile in a cohort of early stage NSCLC patients and correlate the results to patient clinico-pathological data and survival. Angioinvasion was routinely recorded by the pathologist at the initial assessment of the tumor following resection. mTOR was evaluated in 141 early stage (IA-IIB) NSCLC patients (67 - squamous; 60 - adenocarcinoma; 14 - others) using immunohistochemistry (IHC) analysis with an immunohistochemical score (IHS) calculated (% positive cells×staining intensity). Intensity was scored as follows: 0 (negative); 1+ (weak); 2+ (moderate); 3+ (strong). The range of scores was 0-300. Based on the previous study a cut-off score of 30 was used to define positive versus negative patients. The impact of angioinvasion and mTOR expression on prognosis was then evaluated. 101 of the 141 tumors studied expressed mTOR. There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma. Angioinvasion (p=0.024) and mTOR staining (p=0.048) were significant univariate predictors of poor survival. Both remained significant after multivariate analysis (p=0.037 and p=0.020, respectively). Our findings verify angioinvasion and mTOR expression as new biomarkers for poor outcome in patients with early stage NSCLC. mTOR expressing patients may benefit from novel therapies targeting the mTOR survival pathway.
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