Intratumoral Vascular Invasion Research Articles

Association of Mps one binder kinase activator 1 (MOB1) expression with poor disease-free survival in individuals with non-small cell lung cancer.

BackgroundMps one binder kinase activator 1 (MOB1) is a core component of the Hippo signaling pathway and has been implicated as a tumor suppressor. Here, we evaluated the possible relationship of MOB1 expression in non‐small cell lung cancer (NSCLC) to prognosis.MethodsWe retrospectively analyzed 205 lung adenocarcinoma patients treated at Kyushu University Hospital between November 2007 and October 2012. MOB1 expression in tumor cells of surgical specimens was evaluated by immunohistochemistry. Invasive activity of NSCLC cell lines in vitro was measured with a transwell assay.ResultsExpression of MOB1 was classified as high in 105 of the 205 (51.2%) tumor specimens, and such high expression was significantly associated with poor disease‐free survival (P = 0.0161). Among the various clinicopathologic parameters examined, high MOB1 expression was significantly associated only with intratumoral vascular invasion (P = 0.0005). Multivariate analysis also identified high MOB1 expression as a significant independent risk factor for disease‐free survival (P = 0.0319). The invasiveness of H1299 cells in vitro was increased or attenuated by overexpression or knockdown of MOB1, respectively.ConclusionsOur results suggest that MOB1 might promote early recurrence of NSCLC by increasing vascular invasion by tumor cells.Key pointsSignificant findings of the studyWe found that high MOB1 expression in surgical specimens of lung adenocarcinoma was associated with poor disease‐free survival and with intratumoral vascular invasion. MOB1 expression also promoted the invasiveness of NSCLC cells in vitro.What this study addsOur results thus suggest that high MOB1 expression is a risk factor for early postoperative recurrence in lung adenocarcinoma.

Prognostic significance of IMMT expression in surgically-resected lung adenocarcinoma.

BackgroundMitochondrial dysfunction contributes to many types of human disorders and cancer progression. Inner membrane mitochondrial protein (IMMT) plays an important role in the maintenance of mitochondrial structure and function. The aims of this study were to examine IMMT expression in lung adenocarcinoma and evaluate its correlation with clinicopathological parameters and patient prognosis.MethodsIMMT expression was immunohistochemically studied in 176 consecutive lung adenocarcinoma resection tissues, and its correlations with clinicopathological parameters were evaluated. Kaplan‐Meier survival analysis and Cox‐proportional hazards models were used to estimate the effect of IMMT expression on survival.ResultsHigh‐IMMT expression was detected in 84 of 176 (47.7%) lung adenocarcinomas. Levels were significantly correlated with advanced disease stage (stage II and III; P = 0.024), larger tumor size (>3 cm; P = 0.002), intratumoral vascular invasion (P < 0.001), and poorer adenocarcinoma patient prognosis (P = 0.002). Based on 176 patients with adenocarcinoma, multivariate analysis revealed that IMMT expression was an independent predictor of poorer survival (HR, 1.99; 95% confidence interval [CI], 1.06–3.74; P = 0.031). Further, treating A549 cells derived from lung adenocarcinoma, with IMMT siRNA resulted in significantly decreased proliferation.ConclusionHere, we first demonstrated that high‐IMMT expression is related to some clinicopathological parameters, and that its expression is an independent prognostic predictor of poorer survival in patients with lung adenocarcinoma; further studies are required to clarify the biological function of IMMT in lung adenocarcinoma. However, results suggest that this protein could be a novel prognostic indicator and therapeutic target.

Clinicopathologic characteristics of non-small cell lung cancer in patients with smoking-related chronic obstructive pulmonary disease.

The purpose of this study was to clarify the clinicopathologic characteristics of non-small cell lung cancer (NSCLC) patients with smoking-related chronic obstructive pulmonary disease (COPD) and to evaluate the biological behavior of this disease. We investigated the association between smoking-related COPD, the recurrence-free proportion (RFP) and the clinicopathological features of clinical stage I NSCLC patients. Between 2005 and 2014, 218 consecutive patients with clinical stage I NSCLC underwent complete resection with lobectomy or greater and systematic lymph node dissection. Differences in categorical outcomes were evaluated by the χ2 test. RFPs were estimated using the Kaplan-Meier method, and differences were evaluated using the log-rank test. The 5-year RFP of clinical stage I NSCLC patients with smoking-related COPD was 55%, which was significantly lower than in those without smoking-related COPD (85%; p < 0.001). Postoperative pathological factors, including moderate or poor histological differentiation, intratumoral vascular invasion and lymph node metastasis, were detected more often in patients with smoking-related COPD. In adenocarcinoma patients, the 5-year RFP of patients with smoking-related COPD was 47%, which was significantly lower than in those without smoking-related COPD (87%; p < 0.001). The presence of a solid component was more frequently found in patients with smoking-related COPD (p = 0.007). Clinical stage I NSCLC patients with smoking-related COPD have histologically more invasive tumors than those without smoking-related COPD.

Combined pulmonary fibrosis and emphysema predicts recurrence following surgery in patients with stage I non-small cell lung cancer.

The purpose of this study was to clarify the clinicopathologic characteristics of non-small cell lung cancer (NSCLC) patients with combined pulmonary fibrosis and emphysema (CPFE). We investigated the association between CPFE, the cancer survival, and the pathological features of clinical stage I NSCLC patients. Between 2005 and 2014, 218 consecutive patients with clinical stage I NSCLC underwent complete resection with systematic lymph node dissection. A univariate analysis by log-rank tests was performed to determine the risk factors for recurrence, and the Cox proportional hazards regression model was used to identify potential independent predictors. The 5-year recurrence-free proportion of patients with CPFE was 36%, which was significantly lower than in those without CPFE (82%; p<0.001). On multivariate analysis, the presence of CPFE was one of the statistically significant independent predictors for tumor recurrence (p=0.005). Postoperative pathological prognostic factors, including moderate or poor histological differentiation, lymphatic permeation, intratumoral vascular invasion, and lymph node metastasis, were detected more often in patients with CPFE. NSCLC patients with CPFE have histologically more invasive tumors than those without CPFE. In patients with clinical stage I NSCLC, the presence of CPFE was a statistically significant predictor of recurrence.

Clinicopathological Significance of S100A14 Expression in Lung Adenocarcinoma

Background: Several studies have reported that S100A14 plays important roles during different steps of the tumorigenic process and tumor progression of several types of cancer. The aim of the present study was to investigate the clinicopathological and prognostic significance and functional roles of S100A14 in lung adenocarcinoma. Patients and Methods: S100A14 expression was immunohistochemically studied in 166 consecutive resected lung adenocarcinomas, and its correlation with clinicopathological parameters was evaluated. Functional roles of S100A14 in lung adenocarcinoma were investigated based on invasion and migration assays on a small interfering (si)RNA-treated lung adenocarcinoma cell line. Results: S100A14 expression was detected in 82 of the 166 (49.4%) lung adenocarcinomas. S100A14 expression was significantly correlated with sex, poorer tumor differentiation, higher disease stages, larger tumor size, lymph node metastasis, intratumoral vascular invasion, intratumoral lymphatic invasion, pleural invasion, and poorer prognosis. Invasion and wound healing assays showed that S100A14 siRNA knockdown cells had significantly decreased invasion and migration abilities compared with siRNA control cells. Conclusion: S100A14 is expressed in a subset of lung adenocarcinoma, and its expression is related to certain clinicopathological parameters. Furthermore, S100A14 expression was strongly correlated with migration and invasion in lung adenocarcinoma cells.

P1.05-004 Surfactant Protein C is a Prognostic Marker in Resected Non-Small Cell Lung Cancer

The lung cancer cells express genes involved in key points of the lung development. The objective of this study was to determine the prognostic value of expression of embryonic markers in tumor tissue samples from patients with surgically-treated non-small cell lung cancer (NSCLC). Study based on 129 primary tumor samples from 102 patients with surgically-treated NSCLC (99% R0) and 27 lung samples. Expression of the following markers was evaluated by mRNA RT-qPCR assay: CEACAM5, FGFR2b, FRS2, MYCN, SFTPC, SHH, SHP2, and SOX17 in the tumor and lung samples. Statistical analyses included chi-squared tests, non-parametric tests, Kaplan Meier curves, log-rank and Cox regression tests. Patients' characteristics were: mean age 67 ± 8 years, squamous carcinoma (49%), adenocarcinoma (43%), pathological staging: I: 56%, II: 32%, III: 11% and IV: 1%. 18% received adjuvant chemotherapy, 1% radiotherapy and 7% both. CEACAM5 and MYCN were overexpressed in tumor samples related to lung samples (p<0,05), FGFR2b showed similar expression and FRS2, SFTPC, SHH, SHP2 and SOX17 were underexpressed (p<0,05). The squamous carcinomas expressed more FGFR2b, FRS2 and SFTPC (p<0,10), while adenocarcinomas expressed more CEACAM5 (p>0,05). Lymph node involvement was associated with SHH underexpression (p<0,05), intratumoral vascular invasion with CEACAM5 or FGFR2b underexpression (p<0,05) and relapse with SHH (p<0,05) or SFTPC (p=0,09) underexpression. Kaplan-Meier curves of SFTPC were plotted in figure 1. Underexpression of SFTPC in the tumor sample was associated with a 7-fold (7.3; 1.3-40.9) greater active risk of recurrence and a nearly 5-fold (4.9; 1.04-23.2) greater risk of death. Underexpression of SHP2 was associated with a shorter disease-free survival interval (DFS) and overall survival (OS) (p=0.055). Overexpression of FGFR2b or SHH was associated with longer DFS and OS (p<0.05; for SHH, p=0.07 for OS). Combining markers did not provide any additional information. Underexpression of SFTPC in tumor samples was independently associated with worse prognosis.

Clinicopathological Significance of S100A10 Expression in Lung Adenocarcinomas

S100A10, of the S100 protein family, is reported to be involved in cancer cell invasion and metastasis. The aims of the present study were to immunohistochemically examine S100A10 expression in surgically resected lung adenocarcinomas, and evaluate any relationships with clinicopathological parameters and prognosis of patients. S100A10 expression was immunohistochemically studied in 202 consecutive resected lung adenocarcinomas, and its associations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of S100A10 expression on survival. S100A10 expression was detected in 65 of the 202 (32.2%) lung adenocarcinomas, being significantly correlated with poorer differentiation (P =0.015), a higher pathological TNM stage (stages II and III) (P=0.004), more frequent and severe intratumoral vascular invasion (P=0.001), and a poorer prognosis (P=0.030). However, S100A10 expression was not an independent predictor of survival after controlling for clinicopathological factors. The present study reveals that S100A10 is expressed in a subset of lung adenocarcinomas, and this is related to some clinicopathological parameters, although further studies are required to confirm the correlation between S100A10 expression and prognosis of lung adenocarcinoma patients.

Prognostic significance of MYH9 expression in resected non-small cell lung cancer.

IntroductionMyosin-9 (MYH9) belongs to the myosin superfamily of actin-binding motor protein. Recently, MYH9 has been thought to be associated with cancer cell migration, invasion, and metastasis. The aims of this study were to immunohistochemically examine MYH9 expression in surgically resected non-small cell lung cancer (NSCLC), and evaluate its correlations with clinicopathological parameters and the prognosis of patients.MethodsMYH9 expression was immunohistochemically studied in 266 consecutive resected NSCLCs, and its associations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of MYH9 expression on survival.ResultsMYH9 expression was detected in 102 of 266 (38.3%) NSCLCs. MYH9 expression was significantly correlated with the adenocarcinoma histology (P = 0.014), poorer differentiation ((P = 0.033), intratumoral vascular invasion and lymphatic invasion ((P = 0.013 and P = 0.045 respectively), and a poorer prognosis ((P = 0.032). In addition, multivariable analysis revealed that MYH9 expression independently predicted a poorer survival (HR, 2.15; 95%CI, 1.17-3.92; (P = 0.01).ConclusionThe present study revealed that MYH9 is expressed in a subset of NSCLC with a more malignant nature, and its expression is an indicator of a poorer survival probability.

Prognostic impact of vascular and lymphovascular invasion in early lung cancer

The prognostic significance of vascular and lymphatic invasion in non-small-cell lung cancer is under continuous debate. We analyzed the effect of tumor aggressiveness (lymphatic and/or vessel invasion) on survival and relapse in stage I and II non-small-cell lung cancer. We retrospectively analyzed prospectively collected data of 457 patients with stage I and II non-small-cell lung cancer from 1998 to 2008. Specimens were analyzed for intratumoral vascular invasion and lymphovascular space invasion. Overall survival and disease-free survival were estimated using the Kaplan-Meier method, and differences were determined by the logrank test. Cox regression analysis was performed to identify independent risk factors. The incidence of intratumoral vascular invasion was 23.4%, and this correlated significantly with grade of differentiation, visceral pleural involvement, lymphovascular space invasion, and N status. The incidence of lymphovascular space invasion was 5.5%, and this correlated significantly with grade of differentiation, lymph nodes involved, and intratumoral vascular invasion. On multivariate analyses, intratumoral vascular invasion proved to be an significant independent risk factor for overall survival but not for disease-free survival. Lymphovascular space invasion was associated significantly with early tumor recurrence but not with overall survival. Vascular and lymphatic invasion can serve as independent prognostic factors in completely resected non-small-cell lung cancer. Intratumoral vascular invasion and lymphovascular space invasion in early stage non-small-cell lung cancer are important factors in overall survival and early tumor recurrence. Further large scale studies with more recent patient cohorts and refined histological techniques are warranted.

Vascular invasion features affect recurrence in lung adenocarcinoma. Immunohistochemical staining of tumor tissue with E-cadherin antibody in cases with intratumoral vascular invasion. See also Kaseda, K.,et al.

Vascular invasion features affect recurrence in lung adenocarcinoma. Immunohistochemical staining of tumor tissue with E-cadherin antibody in cases with intratumoral vascular invasion. See also Kaseda, K.,<i>et al</i>.

Survival of Patients with Non-Small Cell Lung Cancer According to Lymph Node Disease: Single pN1 vs Multiple pN1 vs Single Unsuspected pN2

This study was designed to describe the characteristics and survival of NSCLC patients treated with surgery and single pN1 disease, multiple pN1, and single unsuspected pN2. In 2005-2009, we treated 378 lung cancer patients with surgery with radical intent; 152 cases were pN1 or pN2. We excluded patients with neoadjuvant treatment, incomplete resection, incomplete lymph node dissection, metastasis, cN2 disease, multiple pN2, SCLC, and lack of PET-CT. All patients were staged with TNM 2010. We included 72 patients: 21 single pN1, 26 multiple pN1, and 25 single unsuspected pN2. Statistical analysis included descriptive statistics, chi-square test, Kaplan-Meier, log-rank test, and Cox proportional hazard model. The sample included 62 men (86 %) and 10 women (14 %), mean age 64 ± 9 years. The three subgroups did not show statistically significant differences in the main characteristics. Adjuvant treatment was performed in 56 patients (78 %). The 5 year overall survival (OS) for single pN1 was 73 %; for multiple pN1, 34 %; and for single unsuspected pN2, 25 % (P = 0.15). The mean OS for single pN1 was 63 ± 6 months; median OS for multiple pN1 was 45 (range, 42-48) months and for single pN2 was 54 (range, 32-77) months. Multivariate analysis found the following negative prognostic factors of OS: for single pN1, age, female sex, and microscopic intratumoral lymphatic and vascular invasion; for multiple pN1, ≤10 lymph nodes resected. Patients with single pN1 had better OS than patients with multiple pN1. Patients with single unsuspected pN2 had OS similar to that of multiple pN1.

Prognostic Impact of Cancer-Associated Stromal Cells in Patients With Stage I Lung Adenocarcinoma

The tumor microenvironment, of which cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are the major cellular components, plays an important role in tumor progression. This study evaluated the significance of podoplanin-positive CAFs and CD204-positive TAMs, which may reflect tumor-promoting CAFs and TAMs, as risk factors for recurrence in patients with stage I lung adenocarcinoma. The expression of podoplanin in CAFs and CD204 in TAMs was analyzed by immunohistochemistry in 304 patients with stage I lung adenocarcinoma who underwent surgical resection between September 1992 and July 2004. The recurrence-free proportion (RFP) was estimated using the Kaplan-Meier method. The presence of podoplanin-positive CAFs and the higher number of CD204-positive TAMs were associated with a lower 5-year RFP (P < .001 and P = .001, respectively). Podoplanin-positive CAFs were an independently statistically significant risk factor for recurrence with the highest hazard ratio (3.474, P = .029, by multivariate Cox proportional hazards model). According to subgroup analyses combining podoplanin-positive CAFs and other independent risk factors (visceral pleural invasion and intratumoral vascular invasion), the 5-year RFPs were 95.6%, 92.3%, 80.5%, and 30.3% (P = .294, P = .067, and P < .001) for patients with zero, one, two, or three risk factors, respectively. Podoplanin-positive CAFs were the most powerful independent risk factor for recurrence in patients with stage I lung adenocarcinoma. Podoplanin-positive CAFs may be useful for identifying patients with a high risk of recurrence who might benefit from adjuvant chemotherapy.

Prognostic Significance of TAZ Expression in Resected Non-Small Cell Lung Cancer

Transcriptional coactivator with PDZ-binding motif (TAZ) is known to bind to a variety of transcription factors to control cell differentiation and organ development. Recently, TAZ has been identified as an oncogene and has an important role in tumorigenicity of non-small cell lung cancer (NSCLC). Therefore, TAZ may present a novel target for the future diagnosis, prognosis, and therapy for lung cancer. We investigated the relationship between TAZ expression and clinicopathological parameters and determined its prognostic significance concerning survival in patients with resected NSCLC. TAZ expression was immunohistochemically studied in 181 consecutive patients with NSCLC and 20 cases of normal lung tissue. The association between expression of TAZ and clinicopathological parameters was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of TAZ expression on survival. TAZ expression was observed in 121 of the 181 (66.8%) NSCLC. TAZ had nuclear and cytoplasmic expression. Clinicopathologically, TAZ expression was significantly associated with lung adenocarcinoma (p = 0. 002), poorer differentiation (p = 0.001), p-tumor, node, metastasis stage (p = 0.001), lymph node metastasis (p = 0.032), intratumoral vascular invasion (p = 0.004), pleural invasion (p = 0.003), adjuvant chemotherapy (p = 0.044), and poorer prognosis (p = 0.002). Multivariable analysis confirmed that TAZ expression increased the hazard of death after adjusting for other clinicopathological factors (hazard ratio, 2.56; 95% confidence interval, 1.39-4.66; p = 0.01). Overall survival was significantly prolonged in TAZ negative group when compared with TAZ positive group (61.8 versus 47.1 months; p < 0.0001), as was disease-free survival (44.3 versus 25.1 months; p < 0.0001). Adjuvant chemotherapy prolonged overall survival among resected NSCLC patients with TAZ positive expression (p = 0.001). This study suggests that TAZ expression is a prognostic indicator of poorer survival probability for patients with resected NSCLC.

Angiolymphatic invasion exerts a strong impact on surgical outcomes for stage I lung adenocarcinoma, but not non-adenocarcinoma

Angiolymphatic invasion (ALI), representing lymphatic invasion (Ly) and intratumoral vascular invasion (V), is considered to be a useful prognostic factor for pathological stage I non-small cell lung carcinoma (NSCLC). However, the types of tumor for which prognoses are most influenced by ALI positivity have not previously been discussed, nor has the question of whether these findings should influence postoperative therapeutic decision-making after complete resection. The present study investigated 195 cases of stage I NSCLC treated by potentially curative surgical resection of the primary tumor and systematic lymphadenectomy. ALI-positive (ALI(+)) results were found in 31.8% of tumors, and 5.1% exhibited both Ly(+) and V(+). Five-year recurrence-free survival was significantly lower in ALI(+) cases (50.6%) than in ALI(−) cases (85.9%; p<0.0001, log-rank test). In particular, 5-year recurrence-free survival rate was only 10.0% for Ly(+)V(+) cases. ALI(+) correlated with high age, male sex, tumor size (>2.0cm), elevated preoperative serum carcinoembryonic antigen level (≥5.0ng/mL), high maximum standard uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) (≥5.0), pleural invasion, and histological classification of non-adenocarcinoma (ADC). According to histopathological subset analyses, ALI(+) was associated with shorter recurrence-free survival than ALI(−) only among ADC patients (p<0.0001, log-rank test), and not among non-ADC patients (p=0.7710). High preoperative serum CEA level, high SUVmax on FDG-PET, pleural invasion, Ly(+), and V(+) were significant risk factors for recurrence in univariate Cox survival analysis among stage I ADC patients. Importantly, Ly(+) and V(+) were identified as independent risk factors for recurrence by multivariate analysis. Histopathological detection of ALI as a risk factor for recurrence should be considered for inclusion in the staging criteria and as additional information for determining postoperative adjuvant treatment of stage I NSCLC, particularly among ADC patients, but not among non-ADC patients.

Influence of Cigarette Smoking on Survival and Tumor Invasiveness in Clinical Stage IA Lung Adenocarcinoma

The objective of this study was to investigate the association between cigarette smoking, cancer survival, and pathological features of clinical stage IA lung adenocarcinoma. Between August 1992 and December 2007, 1,070 consecutive patients with clinical stage IA lung adenocarcinoma underwent complete resection with systematic lymph node dissection. Univariate analysis by log-rank tests was performed to determine unfavorable prognostic factors, and the Cox proportional hazards regression model was used to identify the potential independent predictors. The overall 5-year survival rate of patients with greater than 20 pack-years (PY>20) was 71%, significantly lower than patients with 20 or less pack-years (PY≤20; 86%; p<0.001). Postoperative pathological prognostic factors, including moderate or poor histologic differentiation, lymphatic permeation, intratumoral vascular invasion, visceral pleural invasion, and lymph node metastasis, were detected more often in patients with greater than 20 PY. Sixty-five percent of the patients in this study had pathological stage IA tumors, and their overall 5-year survival rates with 20 or less PY and greater than 20 PY were 97% and 86%, respectively (p<0.001). In patients with clinical stage IA adenocarcinoma, a history of heavy smoking was associated with poor outcomes and was a statistically significant predictor of histologic tumor invasion.

Prognostic factors in patients after lobectomy for p-T1aN0M0 adenocarcinoma

The seventh edition of the TNM Classification of Malignant Tumours was published in 2009. This study was conducted to investigate the prognostic factors of p-T1aN0M0 pulmonary adenocarcinoma, which is the earliest stage defined in the new TNM classification. We retrospectively studied 122 patients who underwent lobectomy at our institution for p-T1aN0M0 adenocarcinoma, as re-categorized in the seventh TNM classification. The patients were separated into groups on the basis of the following clinicopathologic parameters: age, < 70 vs. > 70 years; gender, male vs. female; preoperative serum carcinoembryonic antigen (CEA) level, < 5.0 vs. ≥ 5.0 ng/dl; tumour size, <10 vs. >10 mm; intratumoral vascular or lymphatic invasion, positive vs. negative. Univariate and multivariate analyses of disease-free survival were performed. The median follow-up period was 41.4 months. Univariate analysis showed that prognostic factors such as age, CEA elevation and intratumoral vascular or lymphatic invasion were significant (age, < 70 vs. > 70 years; 97.1% vs. 82.0%, P = 0.0027; preoperative serum CEA level, < 5.0 vs. > 5.0 ng/dl; 93.3% vs. 33.3%, P < 0.0001; intratumoral vascular or lymphatic invasion, positive vs. negative; 31.3% vs. 96.5%, P < 0.0001). Multivariate analysis demonstrated that only intratumoral vascular or lymphatic invasion was a significantly independent prognostic factor (P = 0.0039, Hazard Ratio, 0.066; 95% Confidence Interval, 0.011-0.419). Intratumoral vascular or lymphatic invasion should always be studied and included in the final pathology report in order to consider potential clinical and therapeutic relevance. The efficacy of adjuvant chemotherapy for these patients should also be evaluated in clinical trials.

Prognostic Significance of Nestin Expression in Resected Non-small Cell Lung Cancer

Nestin is a class 6 intermediate filament protein expressed in stem/progenitor cells during CNS development. Nestin expression has been detected in many kinds of tumors and was reported in a recent small-scale study in non-small cell lung cancer (NSCLC). We investigated the relationships between nestin expression and clinicopathologic parameters and determined its prognostic significance concerning survival in patients with resected NSCLC. Nestin expression in tumor cells was studied immunohistochemically in 171 consecutive patients with NSCLC, and associations with clinicopathologic parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of nestin expression on survival. Nestin expression was observed in tumor cell samples in 27 of the 171 patients with NSCLC (15.8%). Nestin had only cytoplasmic expression. Clinicopathologically, nestin expression was significantly associated with squamous cell carcinoma (P = .001), poorer differentiation (P = .007), lymph node metastasis (P = .008), intratumoral vascular invasion (P = .003), intratumoral lymphatic invasion (P = .008), pleural invasion (P = .039), and poorer prognosis (P < .001). Multivariable analysis confirmed that nestin expression increased the hazard of death after adjusting for other clinicopathologic factors (hazard ratio, 2.75; 95% CI, 1.39-5.46). The present study suggests that nestin expression is a prognostic indicator of poorer survival probability for patients with resected NSCLC and may be used as a potential marker for select patients who should receive adjuvant chemotherapy.

Influence of Cigarette Smoking on Histological Subtypes of Stage I Lung Adenocarcinoma

The purpose of this study was to examine the association between cigarette smoking and histological subtypes of lung adenocarcinoma. We reviewed a total of 320 consecutive patients with stage I adenocarcinoma who underwent complete resections with systematic node dissections from January 2004 to December 2006 at the National Cancer Center Hospital East. A statistically significant difference was observed in recurrence-free probabilities between never smokers and ever smokers (3-year recurrence-free probabilities of 95.6% and 88.6%, respectively, p = 0.034). Among adenocarcinoma histological subtypes, only a solid component was significantly more frequent in ever smokers than in never smokers (p < 0.001). Among patients with solid components, significantly more cases had lymphatic permeation (p = 0.007), intratumoral vascular invasion (p < 0.001), and visceral pleural invasion (p < 0.001). Multivariate analysis revealed that ever-smoking history was the only statistically significant independent clinical predictor for a solid component (p < 0.001). Among ever smokers, smoking extent in pack-years of patients with solid components was significantly greater than that of those without solid components (p < 0.001). With respect to predominant subtypes, smoking extent in pack-years of patients with predominantly solid adenocarcinomas was significantly greater than that of patients with predominantly bronchioloalveolar carcinoma, papillary, or acinar adenocarcinomas (all p < 0.001). A greater smoking extent was associated with the presence of adenocarcinoma solid components, which may have more aggressive biological features resulting in poorer outcomes.

Poor Prognostic Factors in Patients With Stage IB Non-small Cell Lung Cancer According to the Seventh Edition TNM Classification

This study investigated poor prognostic factors in patients with stage IB non-small cell lung cancer (NSCLC) according to the seventh edition of the TNM classification. Between July 1992 and December 2004, 1,204 consecutive patients with stage I NSCLC diagnosed based on the sixth edition TNM classification underwent complete resection with systematic node dissection. Of these patients, 434 were reclassified as stage IB according to the seventh edition TNM classification. Univariate analyses were performed using the log-rank test to select prognostic factors. The Cox proportional hazards regression model was used for multivariate analyses to identify independent factors indicating an unfavorable prognosis. On multivariate analyses, two variables were independent significant factors indicating an unfavorable prognosis: presence of intratumoral vascular invasion and presence of visceral pleural invasion. According to subgroup analyses combining these two risk factors, 5-year disease-specific survival probabilities were 93%, 83%, and 73% for patients with zero, one, or two risk factors, respectively. The 5-year disease-specific survival of patients without risk factors was not statistically different from that of patients with stage IA cancer. In addition, the 5-year disease-specific survival curve of patients with two risk factors lay beneath that of patients with T2b or T3N0M0, stage II cancer, and there were no statistically significant differences between them. We identified the presence of intratumoral vascular invasion and the presence of visceral pleural invasion as independent poor prognostic factors in patients with stage IB NSCLC. When these two factors are combined, higher- and lower-risk subgroups can be identified, which will help to personalize adjuvant chemotherapy.

Prognostic impact of intratumoral vascular invasion in non-small cell lung cancer patients

ObjectiveIntratumoral vascular invasion (IVI) in patients with non-small cell lung cancer (NSCLC) has been reported to be a strong independent predictor of recurrence, but it has not been incorporated in...