[Pulmonary Hematoma Likely due to a Contralateral Chest Injury, Requiring Differentiation from Lung Tumor:Report of a Case].

A 23-year-old man was referred to our department for chest abnormal shadow. Computed tomography (CT) of the chest revealed a well-defined 1.2 cm nodule in the S4 segment of the right middle lobe and a well-defined 1.8 cm nodule in the S10 segment of the right lower lobe. The patient was found to have a fracture in the left fifth rib due to the falling accident at playing snowboard, two months before. He was diagnosed with a benign tumor in the right middle lobe and the right lower lobe and was performed surgery. Thoracoscopy revealed a yellowish-brown tumor in the right middle lobe( S4) and a yellow-brown tumor in the right lower lobe( S10). Both lesions were diagnosed as clots by rapid intraoperative pathologic diagnosis. Histopathological diagnosis was an intrapulmonary hematoma.

Primary pulmonary lymphoepithelioma-like carcinoma with positive expression of Epstein-Barr virus and PD-L1: A case report.

INTRODUCTION AND IMPORTANCE: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC) that is classified as a subtype of unclassified carcinoma by the WHO. LELC is usually associated with Epstein-Barr virus (EBV) infection. LELC has often been observed in Southeast Asia; however, it is extremely rare in Japan. CASE PRESENTATION: A 60-year-old Japanese woman presented with an abnormal shadow in the left lung on chest radiography. Chest computed tomography showed a nodule located between the lingular and basal anteromedial segments. A blood test suggested an existing EBV infection, and LELC was suspected preoperatively in the transbronchial lung biopsy. She underwent a lingular and basal bi-segmentectomy. The EBV-encoded small ribonucleic acid in-situ hybridization (EBER-ISH) was positive, and she was diagnosed with LELC. Moreover, programmed death-ligand 1 (PD-L1) expression was moderately positive. No recurrence was observed for 30 months. CLINICAL DISCUSSION: Although LELC has been reported as a low-grade malignancy with a good prognosis, the frequency of PD-L1 expression in LELC seems to be higher than that in other NSCLCs. Moreover, it has been reported that LELC patients with high PD-L1 expression are likely to have early recurrence/metastasis and poor prognosis. CONCLUSION: An investigation of PD-L1 expression for LELC would be useful considering the benefit of PD-1/PD-L1 blockade in patients with pulmonary LELC with high PD-L1 expression. The present case is the first report of LELC with positive expression of EBER-ISH and PD-L1 in Japan.

Downregulated expression of human leukocyte antigen class I heavy chain is associated with poor prognosis in non-small-cell lung cancer.

The aim of this study was to clarify the association between expression of human leukocyte antigen (HLA) class I in non-small-cell lung cancer (NSCLC) cells and patient survival. To address this, immunohistochemical staining for HLA class I was performed on specimens from 111 patients with NSCLC, and overall survival curves were compared using the log-rank test. In addition, multivariate analyses were performed using Cox's proportional hazard model. The cases were divided into 5 classes based on the expression of HLA class I heavy chain and ß2-microglobulin. The overall survival rate for patients with tumors lacking HLA class I heavy chain (30 cases; 27.0%) was significantly decreased. The multivariate analysis demonstrated that the absence of HLA class I heavy chain was an independent predictor of poor prognosis. There was a trend towards an unfavorable prognosis for patients whose tumors did not express ß2-microglobulin (57 cases; 51.4%). Downregulation of HLA class I heavy chain expression was significantly associated with the downregulation of ß2-microglobulin. Cases lacking HLA class I heavy chain as well as ß2-microglobulin expression (23 cases; 20.7%) had a statistically significant unfavorable prognosis compared with other cases. The present findings demonstrate that the lack of HLA class I heavy chain expression in tumor cells is an independent prognostic factor for poor NSCLC survival, and is likely to exert an important influence on immune surveillance in patients.

Personalized siRNA-Nanoparticle Systemic Therapy using Metastatic Lymph Node Specimens Obtained with EBUS-TBNA in Lung Cancer.

Inhibiting specific gene expression with siRNA provides a new therapeutic strategy to tackle many diseases at the molecular level. Recent strategies called high-density lipoprotein (HDL)-mimicking peptide-phospholipid nanoscaffold (HPPS) nanoparticles have been used to induce siRNAs-targeted delivery to scavenger receptor class B type I receptor (SCARB1)-expressing cancer cells with high efficiency. Here, eight ideal therapeutic target genes were identified for advanced lung cancer throughout the screenings using endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) and the establishment of a personalized siRNA-nanoparticle therapy. The relevance of these genes was evaluated by means of siRNA experiments in cancer cell growth. To establish a therapeutic model, kinesin family member-11 (KIF11) was selected as a target gene. A total of 356 lung cancers were analyzed immunohistochemically for its clinicopathologic significance. The antitumor effect of HPPS-conjugated siRNA was evaluated in vivo using xenograft tumor models. Inhibition of gene expression for these targets effectively suppressed lung cancer cell growth. SCARB1 was highly expressed in a subset of tumors from the lung large-cell carcinoma (LCC) and small-cell lung cancer (SCLC) patients. High-level KIF11 expression was identified as an independent prognostic factor in LCC and squamous cell carcinoma (SqCC) patients. Finally, a conjugate of siRNA against KIF11 and HPPS nanoparticles induced downregulation of KIF11 expression and mediated dramatic inhibition of tumor growth in vivoImplications: This approach showed delivering personalized cancer-specific siRNAs via the appropriate nanocarrier may be a novel therapeutic option for patients with advanced lung cancer. Mol Cancer Res; 16(1); 47-57. ©2017 AACR.

Nanoparticle targeted folate receptor 1-enhanced photodynamic therapy for lung cancer.

OBJECTIVE: Despite modest improvements, the prognosis of lung cancer patients has still remained poor and new treatment are urgently needed. Photodynamic therapy (PDT), the use of light-activated compounds (photosensitizers) is a treatment option but its use has been restricted to central airway lesions. Here, we report the use of novel porphyrin-lipid nanoparticles (porphysomes) targeted to folate receptor 1 (FOLR1) to enhance the efficacy and specificity of PDT that may translate into a minimally-invasive intervention for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer. MATERIALS AND METHODS: The frequency of FOLR1 expression in primary lung cancer and metastatic lymph nodes was first analyzed by human tissue samples from surgery and endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA). Confocal fluorescence microscopy was then used to confirm the cellular uptake and fluorescence activation in lung cancer cells, and the photocytotoxicity was evaluated using a cell viability assay. In vivo fluorescence activation and quantification of uptake were investigated in mouse lung orthotopic tumor models, followed by the evaluation of in vivo PDT efficacy. RESULTS: FOLR1 was highly expressed in metastatic lymph node samples from patients with advanced lung cancer and was mainly expressed in lung adenocarcinomas in primary lung cancer. Expression of FOLR1 in lung cancer cell lines corresponded with the intracellular uptake of folate-porphysomes in vitro. When irradiated with a 671nm laser at a dose of 10J/cm2, folate-porphysomes showed marked therapeutic efficacy compared with untargeted porphysomes (28% vs. 83% and 24% vs. 99% cell viability in A549 and SBC5 lung cancer cells, respectively). Systemically-administered folate-porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast. Folate-porphysomes mediated PDT successfully inhibited tumor cell proliferation and activated tumor cell apoptosis. CONCLUSION: Folate-porphysome based PDT shows promise in selectively ablating lung cancer based on FOLR1 expression in these preclinical models.

Overexpression of MAGEA2 has a prognostic significance and is a potential therapeutic target for patients with lung cancer.

Melanoma-associated antigens (MAGE) are expressed in different type of cancers including lung cancer and have been shown to be functionally related to p53 tumor suppressor gene. Little is known about the relationship between MAGE genes and p53 aberrant expression in lung cancer. The aims of this study were to observe the expression of MAGEA2, examine the role of MAGEA2 in lung cancer survival, investigate its correlation between MAGEA2 and p53, and explore its clinicopathologic significance as a prognostic marker. Quantitative reverse transcription-polymerase chain reaction was performed to detect the expression of MAGEA2 using 36 primary tumors and 31 metastatic lymph nodes from patients with lung cancer. The role of MAGEA2 in cancer cell growth and in the regulation of p53 downstream genes were examined using small interfering RNA. The expression of MAGEA2 and p53 were analyzed immunohistochemically using tissue microarray from 353 resected lung specimens. High-level expression of MAGEA2 (High-MAGEA2) was confirmed in lung tumors with high frequency. Inhibiting MAGEA2 expression effectively suppressed cancer cell growth and decreased the expression of p53 downstream target genes in vitro. In adenocarcinoma, High-MAGEA2 was strongly associated with aberrant p53 expression (P<0.001) and was associated with worse clinical outcomes (5-year OS, 87.1% in low vs. 74.1% in high, P=0.014). Aberrant p53 expression was also significant worse prognostic factor (P=0.029). Among the adenocarcinoma patients with wild-type p53, High-MAGEA2 had poorer prognosis than low-level MAGEA2 groups (5-year OS, 90.1% vs. 72.1%, P=0.037), whereas had no difference in p53 aberrant tumors. On multivariate analysis, MAGEA2 was independently associated with survival (hazard ratio; 2.12, P=0.030). In conclusion, suppression of MAGEA2 in lung cancer cells significantly reduced the growth/survival of cancer cells. High-MAGEA2 was identified as an independent prognostic factor in lung adenocarcinoma. Specific inhibition of MAGEA2 may be a promising therapeutic strategy for patients with lung cancer.

SORORIN and PLK1 as potential therapeutic targets in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive type of cancer of the thoracic cavity commonly associated with asbestos exposure and a high mortality rate. There is a need for new molecular targets for the development of more effective therapies for MPM. Using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and an RNA interference-based screening, we examined the SORORIN gene as potential therapeutic targets for MPM in addition to the PLK1 gene, which is known for kinase of SORORIN. Following in vitro investigation of the effects of target silencing on MPM cells, cell cycle analyses were performed. SORORIN expression was analyzed immunohistochemically using a total of 53 MPM samples on tissue microarray. SORORIN was found to be overexpressed in the majority of clinical MPM samples and human MPM cell lines as determined by qRT-PCR. Gene suppression of each SORORIN and PLK1 led to growth inhibition in MPM cell lines. Knockdown of SORORIN showed an increased number of G2M-phase population and a larger nuclear size, suggesting mitotic arrest. High expression of SORORIN (SORORIN-H) was found in 50.9% of all the MPM cases, and there is a tendency towards poorer prognosis for the SORORIN-H group but the difference is not significant. Suppression of SORORIN with PLK1 inhibitor BI 6727 showed a combinational growth suppressive effect on MPM cell growth. Given high-dose PLK1 inhibitor induced drug-related adverse effects in several clinical trials, our results suggest inhibition SORORIN-PLK1 axis may hold promise for the treatment of MPMs.

Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer commonly associated with asbestos exposure that stems from the thoracic mesothelium with high mortality rate. Currently, treatment options for MPM are limited, and new molecular targets for treatments are urgently needed. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and an RNA interference-based screening, we screened two kinesin family members as potential therapeutic targets for MPM. Following in vitro investigation of the target silencing effects on MPM cells, a total of 53 MPMs were analyzed immunohistochemically with tissue microarray. KIF11 and KIF23 transcripts were found to be overexpressed in the majority of clinical MPM samples as well as human MPM cell lines as determined by quantitative RT-PCR. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of KIF11 and KIF23. High expression of KIF11 (KIF11-H) and KIF23 (KIF23-H) were found in 43.4 and 50.9% of all the MPM cases, respectively. Patients who received curative resection with tumors displaying KIF23-H showed shorter overall survival (P=0.0194). These results provide that inhibition of KIF11 and KIF23 may hold promise for treatment of MPMs, raising the possibility that kinesin-based drug targets may be developed in the future.

Overexpression of KIF23 predicts clinical outcome in primary lung cancer patients.

OBJECTIVE: High-level expression of kinesin family member 23 (KIF23), a member of microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division, has been observed in a variety of human malignancies. The aims of the present study were to observe the expression of KIF23 in lung cancer, examine the role of KIF23 in lung cancer cell growth and/or survival by small interfering RNA experiments, and explore its clinicopathologic significance and evaluate KIF23 expression as a prognostic marker. MATERIALS AND METHODS: Quantitative reverse transcription-polymerase chain reaction analysis was performed to detect the expression of KIF23 mRNA using metastatic lymph nodes from patients with advanced lung cancer obtained by endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) and primary lung tumors through surgical sample. The role of KIF23 in cancer cell growth was examined by small interfering RNA experiments. A total of 339 lung cancers were analyzed immunohistochemically on tissue microarrays to examine the expression of KIF23 protein and its clinicopathologic significance. RESULTS: KIF23 transcript was found to be overexpressed in the great majority of metastatic lymph nodes from advanced lung cancers and primary lung tumors. Inhibiting KIF23 expression effectively suppressed lung cancer cell growth. High-level KIF23 expression was observed in 67.8% of the 339 cases. Lung adenocarcinoma patients with tumors displaying a high-level of KIF23 expression was also identified as an independent prognostic factor by multivariate analysis (P=0.0064). CONCLUSION: KIF23 not only provides additional prognostic information for surgical treatment of lung cancer, but may also be a novel therapeutic target for these patients.

A case of Castleman's disease with myasthenia gravis.

A rare case of Castleman's disease with myasthenia gravis is reported. A 55-year-old woman with bilateral ptosis, speech impairment, and severe dyspnea had been previously diagnosed with myasthenia gravis. Computed tomography showed a 5 cm × 3 cm paratracheal mass in the mediastinum, thought to be an ectopic thymoma. Two days after surgical resection, the patient suddenly developed dyspnea. Postoperative myasthenic crisis was diagnosed, and plasmapheresis was performed. Her general condition improved, and her subsequent course was uneventful. The final pathological diagnosis was mediastinal solitary Castleman's disease, hyaline vascular type. Castleman's disease with myasthenia gravis is especially rare. One of the serious complications is postoperative myasthenic crisis. For patients with myasthenia gravis, the rate of postoperative myasthenic crisis seems significantly higher in Castleman's disease patients than in patients with thymic epithelial tumors. Castleman's disease with myasthenia gravis is discussed along with a review of the literature.

Endobronchial closure of a bronchopleural fistula using a fibrin glue-coated collagen patch and fibrin glue.

Bronchopleural fistulas associated with empyema can occur as life-threatening sequelae after pulmonary resection, occurring most frequently after pneumonectomy. Three bronchopleural fistulas, 5-6 mm in diameter, were successfully treated using a fibrin glue-coated collagen patch (FGCCP) and fibrin glue (FG) at the site of a bronchopleural fistula. Through the clinical experiences, we introduce the methodology to perform the endobronchial closure of bronchopleural fistulas.Data were collected by reviewing the clinical charts of patients diagnosed with post-lobectomy bronchopleural fistula at Sapporo Minami-Sanjo Hospital from June 2004 to December 2010. Bronchopleural fistula was diagnosed by means of endoscopic visualization. Three cases of post-lobectomy and one case of post-pneumonectomy bronchopleural fistula were collected.A FGCCP fragment was packed within the fistula, and the fragment grasped with the forceps was kept in this position for approximately a minute, a time during which a FGCCP becomes adhesive, and the patch fragment was released. After releasing the patch fragment, the FG was applied directly on the FGCCP using a two-channel catheter.There have been few reports of the bronchoscopic closure of bronchopleural fistulas using a FGCCP and FG. Closure of small bronchopleural fistulas with the application of a FGCCP and FG may offer a valuable therapeutic alternative.

Method for the validation of immunohistochemical staining using SCID mouse xenografts: expression of CD40 and CD154 in human non-small cell lung cancer.

This report proposes a concept for the standardization of immunohistochemical evaluation. Immunohistochemical staining has several problems associated with the sensitivity of the technical process and standardization of the assessment of potent staining. We provided data focusing on this concept through immunostaining for CD154 in non-small cell lung cancer (NSCLC). We used two types of anti-CD154 antibody as primary antibodies in immunohistochemical staining, as previously reported. Western blot analysis confirmed strong CD154 expression in the cultured cell line PC10, but not in LK2. We also assessed CD154 expression in SCID mouse xenografts of these cell lines. SCID xenograft data on western blot analysis were consistent with those of cultured cell lines. These xenografts could thus be used as positive or negative tissue controls for CD154 immunostaining. Primary antibodies should therefore be confirmed as recognizing target lesions, while control tissue specimens should be objectively confirmed as having target products using another experimental method. Our method would allow results to be unified at more than one laboratory and could act as an objective control assessment method in immunohistochemistry.

Optimal predictive value of preoperative serum carcinoembryonic antigen for surgical outcomes in stage I non-small cell lung cancer: differences according to histology and smoking status.

BACKGROUND: The cutoff value of preoperative serum carcinoembryonic antigen (CEA) levels has not been investigated using appropriate subgroup analyses for non-small cell lung carcinoma (NSCLC). This study was undertaken to determine whether the most predictive preoperative CEA level for risk of recurrence differs according to histological type, and how smoking status influences predictive values in Stage I NSCLC. METHODS: Subjects comprised Stage I NSCLC patients [141 patients with adenocarcinoma (ADC) and 36 with squamous cell carcinoma (SCC)]. RESULTS: In patients with Stage I ADC, recurrence-free survival (RFS) differed most significantly at a preoperative CEA level of 2.5 ng/ml, regardless of smoking status. Cases with preoperative CEA >2.5 ng/ml correlated with male sex, high maximum standard uptake value on (18) F-fluorodeoxyglucose positron emission tomography, poorer histopathological grade, lymphatic invasion, and smoking status. Importantly, preoperative CEA >2.5 ng/ml was identified as an independent risk factor for recurrence (P = 0.0015). Conversely, in patients with SCC, a preoperative CEA level of 3.0 ng/ml was the most predictive threshold. CONCLUSIONS: Thresholds of preoperative CEA should be considered when predicting risk of relapse, even if these levels are within normal limits, as optimal cutoff levels may vary according to histological type.

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 (>2.0 cm), elevated preoperative serum carcinoembryonic antigen level (≥5.0 ng/mL), high maximum standard uptake value (SUVmax) on (18)F-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.

Overexpression of CDC20 predicts poor prognosis in primary non-small cell lung cancer patients.

BACKGROUND: This study examined the expression of CDC20 in human non-small cell lung cancer (NSCLC), explored its clinicopathological significance, and evaluated as a potential prognostic marker. METHODS: A total of 362 cases of NSCLCs were analyzed immunohistochemically on tissue microarrays (TMAs). Additionally, the immunoreactivity of mitotic arrest defective protein 2 (MAD2) was also studied. The clinicopathological implications of these molecules were analyzed statistically. RESULTS: High-level CDC20 protein expression (CDC20-H) was detected in 71 cases (19.6%). Additionally, CDC20-H was correlated with male sex, pT status, pleural invasion, and non-adenocarcinoma (non-ADC) histology. Significant correlation between CDC20 and MAD2 expression was found. NSCLC patients with tumor exhibiting CDC20-H showed significantly shorter 5-year overall survival (P=0.0007). According to subset analyses, CDC20-H was associated with shorter survival than CDC20-L only among ADC patients (P=0.0008), and not among squamous cell carcinoma (SCC) patients (P=0.5100). Importantly, CDC20-H was also identified as an independent prognostic factor in multivariate analysis (P=0.0065). CONCLUSIONS: CDC20 was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with ADC histology. These results provide additional information for determining postoperative adjuvant treatment.

Spontaneous pneumothorax in a patient with dendriform pulmonary ossification: report of a case.

We report herein the rare case of a patient with dendriform pulmonary ossification (DPO) who developed spontaneous pneumothorax. A 33-year-old male with a history of bronchial asthma presented with pneumothorax of the left lung. An intraoperative inspection revealed no findings of bullae in the entire left lung, but inflammatory pleural changes were identified on the interlobular surface of the left lower lobe. In addition, hard, twig-like configurations were clearly palpable in the subpleural parenchyma and were resected. A histological examination showed acicular bone formations containing myeloid tissue and marrow fat in the lung. DPO was thus diagnosed, and the bony spines were considered to have caused a rupture of the elastic fiber layer of the visceral pleura. DPO may thus have been directly responsible for the pneumothorax in this case.

Overexpression of KIAA0101 predicts poor prognosis in primary lung cancer patients.

High expression of KIAA0101 (p15(PAF)/OEATC-1) which contains a proliferating cell nuclear antigen (PCNA)-binding motif, a key factor in DNA repair and/or apoptosis and cell cycle regulation, has been observed in a variety of human malignancies. The aim of this study was to observe the expression of KIAA0101 in human non-small-cell lung cancer (NSCLC), explore its clinicopathological significance and evaluate KIAA0101 expression as a potential prognostic marker. KIAA0101 transcript was found to be overexpressed in the great majority of lung cancers by semi-quantitative RT-PCR. A total of 357 NSCLCs were analyzed immunohistochemically on tissue microarrays. High-level KIAA0101 expression was observed in 33.9% (121 of 357 cases), and correlated with male gender (P<0.0001), tumor progression (pT status) (P=0.0008), lymph node metastasis (pN status) (P=0.0003), non-adenocarcinoma histological classification (P<0.0001), and smoking history (P<0.0001), but not with patient age or pleural invasion. Patients with tumors displaying high-level KIAA0101 expression showed significantly shorter survival (P<0.0001, log-rank test). Similarly, gender, pT status, pN status, pleural invasion, histological classification, and smoking history were significant prognostic markers in univariate Cox survival analysis. Importantly, high-level KIAA0101 expression was also identified as an independent prognostic factor by multivariate analysis (P=0.0320). These results provide additional information for determining postoperative adjuvant treatment of NSCLC.

Pleomorphic carcinoma of the lung arising in a patient with Li-Fraumeni syndrome: report of a case.

We herein report the case of a patient with Li-Fraumeni syndrome (LFS) who developed lung pleomorphic carcinoma. A 28-year-old female patient with a family history of early-onset malignancies was diagnosed with lung carcinoma and treated by surgical resection. Histological examination revealed a heterogeneous tumor with epithelial and mesenchymal components. The final pathological diagnosis was pulmonary pleomorphic carcinoma. In this patient, a constitutional mutation at codon 213 in exon 6 of the p53 gene was identified in the peripheral lymphocytes and the resected tumor, and LFS was suspected. This mutation causes a nonsense mutation (Arg-to-Stop codon) that has been shown to attenuate p53 function. This is the first report of pulmonary pleomorphic carcinoma developing in an LFS patient, and may suggest a relationship between germline p53 mutation and carcinogenesis in pulmonary pleomorphic carcinoma.

18F-FDG uptake in primary lung cancer as a predictor of intratumoral vessel invasion.

OBJECTIVE: This study investigated how fluorodeoxyglucose (FDG) uptake on PET in the primary tumor may predict intratumoral vessel invasion (IVI) in it. METHODS: A total of 512 patients with lung neoplasms determined by a surgical procedure and histopathological diagnosis had undergone FDG-PET scanning. RESULTS: Among the 440 cases confirmed to be malignant, the maximum standardized uptake value (SUV(max)) was significantly lower in IVI-negative cases than IVI-positive cases (P < 0.001). In the substudy on adenocarcinoma (AC), SUV(max) was significantly lower in IVI-negative cases too (P < 0.001), but SUV(max) in squamous cell carcinoma was without significant difference. In addition, IVI was associated with a significantly higher probability of lymph node metastasis (P < 0.001). CONCLUSIONS: This study indicates that a malignant lung tumor with higher SUV(max) has a significantly higher probability of IVI and lymph node metastasis, particularly if the malignancy is an AC.

Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients.

High-level expression of mitotic arrest defective protein 2 (MAD2), a central component of the spindle assembly checkpoint, has been observed in a variety of human malignancies. Aim of the present study was to observe the expression of MAD2 in human non-small-cell lung cancer (NSCLC) and explore its clinicopathologic significance and evaluate MAD2 expression as a prognostic marker. MAD2 transcript was found to be overexpressed in the great majority of lung cancers by semi-quantitative RT-PCR. A total of 358 NSCLCs were analyzed immunohistochemically on tissue microarrays. High-level MAD2 expression was observed in 26.3% (94 of 358 cases), and correlated with male sex (P=0.0002), tumor progression (pT status) (P=0.0009), visceral or parietal pleural invasion (P=0.0151), non-adenocarcinoma, histological classification (P<0.0001), and smoking history (P=0.0022), but not with patient age or lymph node metastasis (pN status). Patients with tumors displaying high-level MAD2 expression showed significantly shorter survival (P<0.0001, log-rank test). Similarly, gender, pT status, pN status, pleural invasion, histological classification, and smoking history were significant prognostic markers in univariate Cox survival analysis. Importantly, high-level MAD2 expression was also identified as an independent prognostic factor by multivariate analysis (P=0.0076). These results provide additional prognostic information for surgical treatment of NSCLC.