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Background Maintenance chemotherapy could prolong overall and/or progression-free survival in advanced NSCLC. S-1 is an oral anticancer agent comprised of tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate. The TORG 0809 study was conducted to evaluate the feasibility and efficacy of maintenance chemotherapy of S-1 following DOC + CDDP in patients with curatively resected stage II and IIIA NSCLC. Methods Patients received three cycles of DOC (60 mg/m2 d1) plus CDDP (80 mg/m2 d1), q3-4w, and subsequently S-1 at 40 mg/m2 twice a day for 14 consecutive days, q3w, for more than 6 months (max 1 year). The primary end point was determination of feasibility, which was defined as the proportion of patients who had completed maintenance for 8 cycles of S-1 or more. If the lower confidence interval (CI) of this proportion was 50% or more, the feasibility of the treatment was considered confirmed. The sample size was set to be 125. Results Between June 2009 and November 2010, 131 patients were enrolled, of whom 129 patients were eligible and assessable. The median age was 63 (23–74 years); PS 0: 107, 1: 22; p-stage IIA: 19, IIB: 30, IIIA: 80; adenocarcinoma: 99, non-adenocarcinoma: 30. Of 129 patients, 109 patients (84.5%) completed three cycles of DOC + CDDP. One hundred and six patients initiated the maintenance S-1 and 66 patients (51.2%, 95% CI: 42.5–59.8) completed eight cycles or more S-1 treatment; this percentage was less than our previously defined criterion for treatment feasibility, since 32 patients terminated maintenance S-1 at three cycles or less. Grade 3/4 toxic effects during the maintenance S-1 included anemia (7.3%), neutropenia (3.7%), anorexia (3.7%), dyspnea (1.8%), infection with neutropenia of grade 0 to 2 (1.8%). Febrile neutropenia was not observed. Conclusions The toxicity level was acceptable, although the results did not meet our criterion for feasibility.

The causes and morphological appearances of human lung cancers are variable. We analyzed thirty seven lung cancer cell lines including thirty adenocarcnima (ADC), three small cell carcinoma (SCLC), one large cell carcinoma (LCC) and one adenosquamous carcinoma (AdSq) with LC/MS and identified less than 500 proteins of each cell line. We compared proteomic profiles between EGFR mutations and K-Ras mutations, smokers and non/less-smokers, and non-small cell carcinoma (NSCLC) and small cell carcinoma (SCLC). Eleven proteins, CALR, KYNU, SLC3A2, ALDH2, PGD, LAP3, DLC1, KIAA0664, ILKAP, ABCA13 and PTGR1 are related to the relationship between cell lines with EGFR mutations and K-Ras mutations and some of them are associated to the signal network of cell cycle. Twelve proteins, PPP2R1B, RAP1A, RPS3, RNF113, TGM2, KIF22, UBA6, IFT122, IFI16, AKR1C1/AKR1C2, RPS5 and AKR1C3 are related to the relationship between cell lines in from non/less-smokers and those from smokers and all proteins are associated to the signal network of cell morphology. Fifteen proteins, ANXA2, P4HB, ACTN4, MSN, ANXA5, IDH2, DPYSL2, DPYSL3, DPYSL5, CKB, IPO8, MAP1B, ETFA, TRIM28 and USP5, are related to the relationship between cell lines of NSCLC and SCLC, and some of them are associated to many signal pathways including cancer. Principle Component Analaysis could separate NSCLC from SCLC distinctly. We also detected common proteins among each group as candidate markers of cancer stem cells. AKR1C1/AKR1C2 was detected as common proteins between EGFR mutations vs K-ras mutations and smokers vs non/less smokers and has been reported as one of cancer stem cell markers. These results suggested that this methodology was very useful to detect not only specific proteins of each group but also protein-related signal pathways. Disclosure All authors have declared no conflicts of interest.

Background Chemokines and their receptors have been shown to play a critical role in cancer growth and metastasis. In particular, recent data have suggested that the chemokine CXCL12 and its receptor CXCR7 (also known as RDC1), which has been recently identified as a chemokine receptor, have key functions in promoting tumor development and progression. However, there is little information regarding their expression and clinical relevance in gastric cancer. Here we investigated for the first time the effects of combined CXCR7 and CXCL12 expression on the prognosis of patients with gastric cancer. Methods We studied CXCL12 and CXCR7 protein expression in 221 specimens of primary gastric cancer using immunohistochemistry, and investigated the relationaship between CXCL12/CXCR7 expression and clinicopathological features and clinical outcomes. Results Patients were categorized into four groups according to CXCR7 and CXCL12 expression: low CXCR7/low CXCL12, high CXCR7/low CXCL12, low CXCR7/high CXCL12, and high CXCR7/high CXCL12. No significant differences existed in age, gender, histology, tumor location, lymphovascular invasion among the four groups. However, high CXCR7/high CXCL12 expression in tumor cells was significantly associated with invasion depth of the tumor (T status; P 5 cm (P = 0.006) compared to tumors with low CXCR7/low CXCL12 expression or high CXCR7/low CXCL12–low CXCR7/high CXCL12 expression. Furthermore, patients with high CXCR7/high CXCL12 expression had the worst prognosis (5-year survival rate 30.6%; median, 2.3 years; range, 0.1 - 5.7 years) compared to those of other patient groups (5-year survival rate, 52.4%; median, not reached; log-rank test, P = 0.008) . Conclusions CXCR7 and CXCL12 are useful prognostic factors in gastric cancer, and the combination of high CXCR7 protein expression with high CXCL12 expression suggests a dismal prognosis. Disclosure All authors have declared no conflicts of interest.

7012 Background: Maintenance chemotherapy could prolong overall and/or progression-free survival in advanced NSCLC. S-1 is an oral anticancer agent comprised of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate. The TORG 0809 study was conducted to evaluate the feasibility and efficacy of maintenance chemotherapy of S-1 following DOC+CDDP in patients (pts) with curatively resected stage II and IIIA NSCLC. Methods: Pts received 3 cycles of DOC (60mg/m2 d1) plus CDDP (80mg/m2 d1), q3-4w, and subsequently S-1 at 40mg/m2 twice a day for 14 consecutive days, q3w, for more than 6 months (max 1 year). The primary endpoint was determination of feasibility, which was defined as the proportion of pts who had completed maintenance for 8 cycles of S-1 or more. If the lower confidence interval (CI) of this proportion was 50% or more, the feasibility of the treatment was considered confirmed. The sample size was set to be 125. Results: Between Jun 2009 and Nov 2010, 131 pts were enrolled, of whom 129 pts were eligible and assessable. The median age was 63 (23-74 years); PS 0: 107, 1: 22; p-stage IIA: 19, IIB: 30, IIIA: 80; adenocarcinoma: 99, non-adenocarcinoma: 30. Of 129 pts, 109 pts (84.5%) completed 3 cycles of DOC+CDDP. 106 pts initiated the maintenance S-1 and 66 pts (51.2%, 95% CI: 42.5-59.8) completed 8 cycles or more S-1 treatment; this percentage was less than our previously defined criterion for treatment feasibility, since 32 pts terminated maintenance S-1 at 3 cycles or less. Grade 3/4 toxicities during the maintenance S-1 included anemia (7.3%), neutropenia (3.7%), anorexia (3.7%), dyspnea (1.8%), infection with neutropenia of grade 0 to 2 (1.8%). Febrile neutropenia was not observed. One pt developed interstitial pneumonia and sepsis, resulting in treatment-related death. Recurrence-free survival data will be presented. Conclusions: The toxicity level was acceptable, although the results did not meet our criterion for feasibility. Modification of the treatment schedule of maintenance S-1, such as a 2-week rest period rather than 1-week, might improve treatment compliance.

Nanotechnologies are in development for monitoring drug delivery and therapeutic effect for cancer. However, tumor-targeted multifunctional nanoparticles for imaging of and therapy of lung cancer are not available. The Epidermal growth factor receptor (EGFR) is overexpressed in approximately 80% of non-small cell lung cancer (NSCLC) and is a target for novel therapeutics, however, the clinical results using EGFR inhibitors for NSCLC treatment had mixed results. These results indicate that EGFR expression or its mutational status is solely not a reliable marker to determine the outcome. Therefore, we have developed liposome (120nm) encapsulated with colloidal gold that are conjugated to therapeutic anti-EGFR antibodies (Katayama Chemical Industries Co. Ltd. Osaka, Japan) to determine the molecular specific imaging of NSCLC. The colloidal gold is used for optical imaging and the anti-EGFR antibody for therapy. In the present study, we investigated in vitro effect of these liposomes on EGFR-expressing (HCC827 and H1299) and EGFR-null (H520) NSCLC cells. EGFR-targeted liposome exhibited a strong antitumor effect on EGFR-expressing NSCLC cells. On the other hands, no significant growth inhibitory effects were observed on non-targeted liposome-treated cells. Intriguingly, treatment with EGFR-targeted liposome resulted in significantly higher cell death as compared with anti-EGFR antibody and liposome alone. Furthermore, reflected polarizing microscopy showed that the concentration of EGFR-targeted liposome bound to EGFR-expressing NSCLC cells increased, but EGFR-null cells did not. When EGFR was inhibited pharmacologically, the binding efficiency of EGFR-targeted liposome was attenuated on EGFR-expressing NSCLC cells. These findings indicate that EGFR-targeted liposome are selectively bound and delivered to EGFR expressing NSCLC cells but not the EGFR-null NSCLC cells. We are currently determining in vivo effect of EGFR-targeted liposome using subcutaneous HCC827 and H520 tumor models. Our findings demonstrated that EGFR-targeted liposome is a promising agent for therapy and molecular imaging of NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2904. doi:1538-7445.AM2012-2904

The performance of a fluorescence imaging device was compared with conventional white-light bronchoscopy in 100 patients with lung cancer, 46 patients with resected stage I non-small cell lung cancer, 10 patients with head and neck cancer, and 67 volunteers who had smoked at least 1 pack of cigarettes per day for 25 years or more. Using differences in tissue autofluorescence between premalignant, malignant, and normal tissues, fluorescence bronchoscopy was found to detect significantly more areas with moderate/severe dysplasia or carcinoma in situ than conventional white-light bronchoscopy with a similar specificity. Multiple foci of dysplasia or cancer were found in 13–24% of these individuals. Fluorescence bronchoscopy may be an important adjunct to conventional bronchoscopic examination to improve our ability to detect and localize premalignant and early lung cancer lesions.

Inactivation of the p16 and ESR1 tumor suppressor genes by promoter lesion methylation has been reported in many tumor types, including lung cancer. We examined the blood of 95 non-small cell lung cancer patients (66 cases of adenocarcinoma, 23 of squamous cell carcinoma and 6 of large cell carcinoma) and 30 controls consisting of normal subjects and benign disease patients to determine the methylation ratios of p16 and ESR1 using real-time PCR. For both genes, there was a statistically significant difference in the methylation ratio between non-small cell lung cancer patients and controls (p16; p

10588 Background: Gastrin-releasing peptide receptors (GRPR) are over-expressed in several neoplasms and can play a critical role in tumor cell survival in preclinical models. A Phase I trial of RC...

10601 Background: The EGFR mutation status is a validated biomarker for the stratification of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) treatment in patients with non-small-cell lung cancer (NSCLC...

10556 Background: Epidermal growth factor receptor (EGFR) mutations predict benefit from EGFR tyrosine kinase inhibitors (TKI) in non-small cell lung cancer (NSCLC), however, only 70-80% will respo...

7552 Background: In 2010, the results of the LETS study demonstrated noninferiority for overall survival (OS) less than a predefined stopping boundary at the preplanned interim analysis (protocol-specified noninferiority margin, 1.33) (JCO 2010 28:5240). At the start of this study, we determined that a 2-year follow up would be required. Here, we report the updated results of OS. Methods: In the LETS study, chemotherapy-naive patients with advanced stage (IIIB/IV) non-small cell lung cancer (NSCLC), Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1, and adequate organ functions were randomly assigned to receive either carboplatin AUC (5 mg/ml/min) on day 1 plus oral S-1 (80 mg/m2/day; 40 mg/m2 b.i.d.) on days 1–14 or carboplatin AUC (6 mg/ ml/min) plus paclitaxel (200 mg/m2) on day 1 every 21 days. OS was evaluated as the primary endpoint (ITT; n = 564) in the carboplatin/S-1 arm (n = 282) and carboplatin/paclitaxel arm (n = 282). This analysis used a Cox proportional hazards model ad...

MicroRNAs (miRNAs) belong to a class of the endogenously expressed non-coding small RNAs which primarily function as gene regulators. Growing evidence suggests that microRNAs have a significant role in tumor development. Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains the leading cause of cancer related deaths worldwide. Although EGFR signaling is important and well studied with respect to NSCLC progression, little is known about how miRNAs mediate EGFR signaling to modulate tumorigenesis. In this study, we identified miRNAs that directly regulate the EGFR gene expression. We employed computational tools such as Pictar and Target Scan, and putative targets of 88 miRNAs were identified within the EGFR mRNA. Then, we analyzed the expression of EGFR in miRNAs-transfected human lung cancer cells (H3255, A549, Hcc827) by real time-PCR methods. In addition, we performed argonaute (AGO) IP experiments to ascertain whether these algorithmically predicted miRNA targets are biologically true targets in EGFR. Convincingly, we found that two miRNAs directly regulated the EGFR and both of these miRNAs also inhibited cell growth in cell viability assays. Identifying microRNA regulators of EGFR may contribute in development of novel therapeutics, and non-invasive early detection biomarkers for NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4997. doi:10.1158/1538-7445.AM2011-4997

Large cell neuroendocrine carcinoma (LCNEC) is a subtype of large cell carcinoma (LCC), which has a neuroendocrine feature like small cell lung carcinoma (SCLC). We applied a novel emerging proteomic method using tissues to identify characteristic proteins of LCNEC. Proteins from cancer cells, which collected from formalin fixed paraffin-embedded (FFPE) tissues by laser microdissection were extracted and subjected to liquid chromatography / mass spectrometry. Proteins identified by database search were semi-quantified and subjected further to statistical evaluation. We identified three characteristic proteins of LCNEC, aldehyde dehydrogenase 1 family, member A1 (AL1A1), aldo-keto reductase family 1, member C1 (AK1C1) and C3 (AK1C3) that have been considered as some of cancer stem cell markers. Immunohistochemical verification showed those proteins correlated well with the frequency of immunopositive cells with AL1A1 the greatest. These results suggest that candidate biomarkers of LCNEC are related to cancer stem cells, consistent with its undifferentiated and aggressive nature. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5098. doi:10.1158/1538-7445.AM2011-5098

e17505 Background: Patients with large cell neuroendocrine carcinoma of the lung (LCNEC) are considered to have poor prognosis. This study was undertaken to evaluate the efficacy of perioperative c...

7081 Background: Photodynamic therapy (PDT) is recommended as a treatment option for centrally located early lung cancers (CLELCs), meaning roentgenographically occult squamous cell carcinomas that...

e17506 Background: Cisplatin-based ACT improves survival in patients with completely resected NSCLC. By immunohistochemistry (IHC), cisplatin-based ACT, as compared with observation, significantly ...

e18013 Background: Although adenocarcinoma (Ad) histology and smoking status are now recognized as possible prognostic factors in advanced NSCLC, the distribution of both extensively overlaps. We a...

10542 Background: Activating EGFR mutations have become a backbone in the therapy alogrithm for NSCLC as mutations predict significantly better response and survival to EGFR TKIs. The most common EGFR mutations in NSCLC are exon 19 deletions and the exon 21 L858R point mutation. Among the exon 19 deletions, E746-A750 occurs in 61% of cases. In this study we compared novel IHC antibodies for E764-A750 and L858R to direct DNA sequencing in specimens from Japanese patients with NSCLC treated with gefitinib. Methods: IHC using the E746-A750 and L858R mutation specific antibodies (Cell Signaling Technologies, Danvers, MA) was performed on resected NSCLC Japanese patients who were subsequently treated with gefitinib at relapse. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21. Results: DNA sequencing of all 70 patients showed exon 19 deletions in 18 patients (25.7%), 11 had a deletion at E746-A750, exon 20 mutations in 18 patients, exon 21 mutations in 12 (17.1%), and exon 18 mutations...

7563 Background: EGFR mutation status has emerged to be a validated predictive biomarker for the response to EGFR-tyrosine kinase inhibitors (EGFR-TKI) treatment in non-small cell lung cancer. Howe...

It is very important to elucidate the mechanism of action and identify the molecular determinant of photodynamic medicine, in order to increase the number of clinical applications of photodynamic therapy (PDT) and perform personalized medicine. We have previously reported that PDT using some photosensitizers, such as phthalocyanine 4 (Pc 4) damages the anti-apoptotic protein Bcl-2, and that Bcl-2 is a molecular PDT target using a mitochondrion-targeting photosensitizer. In this study, we examined the molecular targets of Photofrin-PDT and NPe6-PDT, which are approved for early stage lung cancers by the Japanese Ministry of Health Labor and Welfare, by evaluating the photodamage to Bcl-2 using Western blot analysis. Our results showed that Photofrin-PDT damaged Bcl-2, induced morphologically typical apoptosis, and demonstrated equal sensitivity between MCF-7c3 cells (human breast cancer cells expressing stably transfected procaspase-3) and Bcl-2 overexpressing cells, MCF-7c3-GFP-Bcl-2 cells, with a clonogenic assay. However, NPe6-PDT did not damage Bcl-2 and took longer to induce typical apoptosis compared with Photofrin-PDT. MCF-7c3-GFP-Bcl-2 cells were considerably more resistant to the lethal effects of NPe6-PDT than parental MCF-7c3 cells. In conclusion, Photofrin-PDT damages different molecular targets, and our data indicate that the extent of Bcl-2 photodamage can determine the sensitivity of cancer cells to apoptosis and to overall cell killing caused by PDT using Photofrin, but not the lysosomal targeting NPe6. The application of these findings to clinical PDT may depend on the levels of the Bcl-2 proteins in the tumor being treated, and the tailor-made medicine based on the Bcl-2 photodamage may overcome any resistance afforded by elevated amounts of Bcl-2.

7514 Background: Total number of lymph-nodes has recently proven prognostic in early breast and colorectal cancer. In this study we retrospectively evaluated the prognostic impact of the number of resected and involved lymph-nodes on the survival of stage I-III NSCLC. Methods: A series of 928 consecutive NSCLC pts who underwent complete lobectomy, bilobectomy or pneumonectomy with lymph-nodes dissection from 1/2000 to 11/2007 at Tokyo Medical University was eligible. Log rank and Cox proportional hazard model was used to estimate survival rates and relative risks. Results: Demographics are as follows: median age: 65.0 (22–87yrs), sex: 547 males and 381 females, median follow-up time: 2.5 yrs, clinical stage: 765 stage I, 84 stage II and 76 stage III, histology: 684 adenocarcinoma, 182 squamous cell carcinoma, and 62 others, operation: 870 lobectomy, 42 bilobectomy and 16 pneumonectomy, mean number of resected LN: 15 (1–49), mean number of involved LN: 0.9 (0–22). We observed a statistically significant increasing trend in overall survival (OS) between 0–3 and 4 and more of number of involved LN (P No significant financial relationships to disclose.

Equipment has been developed for the early-stage diagnosis and treatment of cancer using an excimer dye laser. The excimer laser beam is obtained by exciting XeCl. A 405 nm beam tuned by DPS dye is used for tumour localization and a 630 nm beam obtained with a rhodamine B dye is used for treatment. The equipment was applied clinically on the basis of extensive experimental research. Effectiveness for cancer localization was examined in 11 cases: four were early stage (three lung cancer and one vocal cord cancer), four were stage I, two were stage III and one was stage IV. All cases were squamous cell carcinoma except for one case of adenocarcinoma. Fluorescence was recognized in all lesions and the equipment was effective for localization.

Photodynamic therapy (PDT) using hematoporphyrin derivative (HpD) has been performed in 139 lesions of 115 lung cancer cases since 1980. The efficacy of and indication for PDT were discussed in this paper. Twenty-six cases were early stage lung cancer and 17 were stage I, 11 were stage II, 42 were stage III and 19 were stage IV, respectively. Complete remission was obtained in early stage cases with small lesion, however incomplete remissions or tumor recurrences were observed in large extent lesions.Opening of obstructed bronchus was obtained in the advanced lung cancer cases and improvements of performance status were obtained. It was also possible to increase the operability and to reduce the extent of resection area in the advanced cases.This modality has more possibilities in the treatment of malignant tumors in future.

Background: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) predict better outcome to EGFR tyrosine kinase inhibitors. The most common mutations are exon 19 deletions (most frequently E746–A750) and L858R point mutation in exon 21. Here, we evaluated the accuracy of novel EGFR mutation-specific antibodies in a Japanese cohort with NSCLC and compared with direct DNA sequencing and clinical outcome. Materials and Methods: Immunohistochemistry (IHC) using antibodies specific for the E746–A750 and L858R mutations in EGFR was performed on tissue microarrays of tumors from 70 gefitinib treated NSCLC patients. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21. Results: DNA sequencing showed EGFR mutations in 41 patients (58.6%) and exon 19 deletions in 18 patients (25.7%), 11 of 18 (61%) had a deletion in the range of E746–A750 and 12 (17.1%) had exon 21 mutations (L858R). IHC showed, for the E746–A750 and L858R mutations, sensitivity (81.8 and 75%), specificity (100 and 96.6%), positive predictive value (100 and 81.8%), and negative predictive value (96.7 and 94.9%). Analysis for objective response rates and survival were not correlated to IHC staining, although the combined staining showed nonsignificant trends toward better overall survival for patients with EGFR mutations. Conclusions: The mutation-specific IHC antibodies have high sensitivity and specificity for predefined EFGR mutations and may be suitable for screening for these predefined mutations. However, negative IHC results require further mutation analyses before excluding EGFR-targeted therapy.

Introduction:The appropriate therapeutic strategy and postoperative management for patients with stage IA non–small-cell lung cancer (NSCLC) still remain a matter of debate because of the prognostic heterogeneity of this population, including the risk of cancer recurrence. The objective of the current study was to identify the clinicopathological factors that affect overall prognosis and cancer recurrence of stage IA NSCLC.Methods:We reviewed the data of 532 patients in whom complete resection of stage IA NSCLC had been performed. Overall survival and recurrence-free proportion (RFP) were estimated using the Kaplan–Meier method. RFP was estimated from the date of the primary tumor resection to the date of the first recurrence or last follow-up. We performed univariate and multivariate analyses to determine the independent prognostic factors.Results:On multivariate analyses, three variables were shown to be independently significant recurrence risk factors: histological differentiation (hazard ratio [HR] = 1.925), blood-vessel invasion (HR = 1.712), and lymph-vessel invasion (HR = 1.751). On subgroup analyses combining these risk factors, the 5-year RFP was 91.3% for patients with no risk factors, 79.5% for those with either poorly differentiated carcinoma or vascular invasion, (p < 0.001 for both), and 62.9% for those with both poorly differentiated carcinoma and vascular invasion (p = 0.068).Conclusion:These results indicated that vascular invasion and tumor differentiation have a significant impact on the prediction of cancer recurrence in patients with stage IA NSCLC. Patients with these predictive factors of recurrence may be good candidates for adjuvant chemotherapy.

Background The purpose of the present study was to determine the nodal spread patterns of pN2 non-small cell lung cancer (NSCLC) according to tumor location, and to attempt to evaluate the possible indications of selective lymph node dissection (SLND). Methods We retrospectively analyzed nodal spread patterns in 207 patients with NSCLC of less than 5 cm with N2 involvement. Results The tumor location was right upper lobe (RUL) in 79, middle lobe in 12, right lower lobe (RLL) in 40, left upper division (LUD) in 41, lingular division in 11, and left lower lobe (LLL) in 24. Both RUL and LUD tumors showed a higher incidence of upper mediastinal (UM) involvement (96 and 100 %, respectively) and a lower incidence of subcarinal involvement (15 and 10 %, respectively) than lower lobe tumors (UM; RLL 60 %, LLL 42 %; subcarinal: RLL 60 %, LLL 46 %, respectively). Among the patients with 24 right UM-positive RLL and 10 left UM-positive LLL tumors, 2 showed negative hilar, subcarinal, and lower mediastinal involvement, and cT1, suggesting that UM dissection may be unnecessary in lower lobe tumors with no metastasis to hilar, subcarinal, and lower mediastinal nodes on frozen sections according to the preoperative T status. Among the patients with 12 subcarinal-positive RUL and 4 subcarinal-positive LUD tumors, one showed negative hilar or UM involvement, suggesting that subcarinal dissection may be unnecessary in RUL or LUD tumors with no metastasis to hilar and UM nodes on frozen sections. Conclusions The present study appears to provide one of the supportive results regarding the treatment strategies for tumor location-specific SLND.

The Tokyo Medical University Hospital in Japan and the Lund University hospital in Sweden have recently initiated a research program with the objective to impact on patient treatment by clinical disease stage characterization (phenotyping), utilizing proteomics sequencing platforms. By sharing clinical experiences, patient treatment principles, and biobank strategies, our respective clinical teams in Japan and Sweden will aid in the development of predictive and drug related protein biomarkers. Data from joint lung cancer studies are presented where protein expression from Neuro- Endocrine lung cancer (LCNEC) phenotype patients can be separated from Small cell- (SCLC) and Large Cell lung cancer (LCC) patients by deep sequencing and spectral counting analysis. LCNEC, a subtype of large cell carcinoma (LCC), is characterized by neuroendocrine differentiation that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological distinction between LCNEC and SCLC has so far been problematic, leading to adverse clinical outcome. An establishment of protein targets characteristic of LCNEC is quite helpful for decision of optimal therapeutic strategy by diagnosing individual patients. Proteoform annotation and clinical biobanking is part of the HUPO initiative (http://www.hupo.org) within chromosome 10 and chromosome 19 consortia. Electronic supplementary material The online version of this article (doi:10.1186/s40169-014-0038-x) contains supplementary material, which is available to authorized users.

Background In the new pathologic classification of lung adenocarcinoma proposed by IASLC/ATS/ERS in 2011, lepidic type adenocarcinomas are constituted by three subtypes; adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and lepidic predominant invasive adenocarcinoma (LPIA). Although these subtypes are speculated to show sequential progression from preinvasive lesion to invasive lung cancer, changes of protein expressions during these processes have not been fully studied yet. This study aims to glimpse a proteomic view of the early lepidic type lung adenocarcinomas. Methods A total of nine formalin-fixed and paraffin-embedded (FFPE) lepidic type lung adenocarcinoma tissues were selected from our archives, three tissues each in AIS, MIA and LPIA. The tumor and peripheral non-tumor cells in these FFPE tissues were collected with laser microdissection (LMD). Using liquid chromatography-tandem mass spectrometry (MS/MS), protein compositions were compared with respect to the peptide separation profiles among tumors collected from three types of tissues, AIS, MIA and LPIA. Proteins identified were semi-quantified by spectral counting-based or identification-based approach, and statistical evaluation was performed by pairwise G-tests. Results A total of 840 proteins were identified. Spectral counting-based semi-quantitative comparisons of all identified proteins through AIS to LPIA have revealed that the protein expression profile of LPIA was significantly differentiated from other subtypes. 70 proteins including HPX, CTTN, CDH1, EGFR, MUC1 were found as LPIA-type marker candidates, 15 protein candidates for MIA-type marker included CRABP2, LMO7, and RNPEP, and 26 protein candidates for AIS-type marker included LTA4H and SOD2. The STRING gene set enrichment resulted from the protein-protein interaction (PPI) network analysis suggested that AIS was rather associated with pathways of focal adhesion, adherens junction, tight junction, that MIA had a strong association predominantly with pathways of proteoglycans in cancer and with PI3K-Akt. In contrast, LPIA was associated broadly with numerous tumor-progression pathways including ErbB, Ras, Rap1 and HIF-1 signalings. Conclusions The proteomic profiles obtained in this study demonstrated the technical feasibility to elucidate protein candidates differentially expressed in FFPE tissues of LPIA. Our results may provide candidates of disease-oriented proteins which may be related to mechanisms of the early-stage progression of lung adenocarcinoma. Electronic supplementary material The online version of this article (doi:10.1186/s40169-015-0064-3) contains supplementary material, which is available to authorized users.