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: 3.74). 06/2007; 56(3):341-8. DOI: 10.1016/j.lungcan.2007.01.019
Source: PubMed

ABSTRACT 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 01/2013; 6(4):598-612. · 1.78 Impact Factor
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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.
    Lung cancer (Amsterdam, Netherlands) 07/2011; 75(2):217-22. DOI:10.1016/j.lungcan.2011.06.012 · 3.74 Impact Factor
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    • "These findings supported previous observations [22] [33] [34]. "
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    ABSTRACT: CD133 is one of the most representative cancer stem cell markers. This study evaluated the potential prognostic value of CD133 expression in stage I lung adenocarcinomas (ADC). Tumors from 177 patients were immunohistochemically examined for CD133 expression, and their associations with disease recurrence were analyzed. Also, the potential prognostic value of combining CD133 expression with proliferating activity measured by immunohistochemical expression of Ki-67 and vessel involvement was evaluated. CD133 high expressers showed a significantly higher risk of recurrence than CD133 low expressers: 5-year disease-free survival (DFS) rate 77.2% vs. 95.1% (p=0.004), adjusted Hazard ratio (HR) 4.37, 95% Confidence Interval (CI) 1.30-14.71 (p=0.017). CD133 high expressers having strong proliferating activity and/or with vessel invasion showed a higher risk of recurrence: 5-year DFS rate 66.5% in CD133 high/Ki-67 high expressers vs. 93.2% in the other types (p<0.001), adjusted HR 8.39, 95% CI 2.65-26.54 (p<0.001): 5-year DFS rate 51.0% in CD133 high expressers with vessel invasion vs. 92.9% in the other types (p<0.001), adjusted HR 4.50, 95% CI 1.51-13.34 (p=0.007): 5-year DFS rate 53.9% in CD133 high/Ki-67 high expressers with vessel invasion vs. 91.2% in the other types (p<0.001), adjusted HR 9.32, 95% CI 3.42-25.39 (p<0.001). In conclusion, the level of CD133 expression is an independent prognostic marker and its combination with proliferating activity and/or vessel invasion could have excellent prognostic value to predict postoperative recurrence in patients with stage I lung ADC.
    International journal of clinical and experimental pathology 01/2010; 4(1):32-42. · 1.78 Impact Factor
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