What factors determine the survival of patients with an acute exacerbation of interstitial lung disease after lung cancer resection?

PURPOSES: Acute exacerbation of interstitial pneumonia (AEIP) is a leading cause of death after lung cancer resection in patients with interstitial lung disease. METHODS: We retrospectively analyzed 1763 patients with non-small cell lung cancer with a clinical diagnosis of interstitial lung disease (ILD) who underwent lung cancer resection between 2000 and 2009 at 61 hospitals in Japan. AEIP occurred in 164 of 1763 (9.3%) patients with a mortality rate of 43.9% (72/164). Univariate and multivariate analyses were carried out to identify possible risk factors of fatal AEIP. We then analyzed the 164 patients who developed postoperative AEIP and identified the preoperative and postoperative risk factors. RESULTS: A multivariate regression analysis identified that the sex, percent vital capacity, neoadjuvant radiation, preoperative history of AEIP, preoperative use of steroids, usual interstitial pneumonia pattern on CT, and surgical procedures were independent preoperative risk factors for death due to AEIP. ILD patients with emphysema somehow showed a lower risk of fatal AEIP than those without emphysema in this study. CONCLUSIONS: This study revealed eight risk factors for fatal AEIP.

[Lung Segmentectomy Using Video-assisted Thoracic Surgery for Lung Cancer in a Patient with Situs Inversus Totalis].

The case was 83-year-old man who had complete situs inversus, and was pointed out to have peripheral adenocarcinoma with the size of 1.8 cm at the left upper lobe( S3). Because of severe emphysema and other multiple comorbidities, left S3 segmentectomy with hilar lymph node sampling was performed using video-assisted thoracic surgery (VATS). Preoperatively, the simulation of operation was performed using the 3 dimension computed tomography images of pulmonary arteriovenous and bronchus (3DCTAB). Postoperative course was uneventful. 3DCTAB was thought to be useful in understanding the anatomical location of pulmonary arteriovenous and bronchus directly, and in performing segmentectomy in the case of situs inversus like this.

[Current surgical treatment of primary chest wall tumor].

Primary chest wall tumor is relatively rare. According to the annual report by The Japanese Association for Thoracic Surgery in 2012, 447 primary chest wall tumors were resected in 2010. It was only 0.66% of the total number of operations in general thoracic surgery in Japan. From January 1992 to December 2012, 3,022 cases in general thoracic surgery were operated in our department. Of these, 30 patients (1%) with primary chest wall tumor were surgically treated. We retrospectively reviewed the medical records of them and investigated the details of this tumor. The patients group included 11 males and 19 females, with a mean age 57.6 years (range, 16 to 79 years). The majority of these patients were referred to us because of radiographical abnormalities on chest X-ray( 56.7%) or clinical symptoms( 33.3%). The operative procedure was tumor extirpation in 25 cases and chest wall resection in 5 cases. Histologically, 23 cases (76.7%) were benign tumors, 7 cases (23.3%) were malignant tumors. Malignant tumors included aggressive and poor prognostic cases such as malignant fibrous histiocytoma or malignant peripheral nerve sheath tumor, on the other hand, extremely rare tumor with low grade malignancy such as parachordoma arising from the chest wall soft tissue was included. In conclusion, although, the standard therapy for malignant primary chest wall tumors has not been established, aggressive surgical resection remains the treatment of choice and to provide an accurate diagnosis.

Probably the Mycobacterium avium Complex around the Staple Line Exacerbated after Radiation Therapy.

The space around the staple line after lung surgery is at high risk of nontuberculosis Mycobacterium pulmonary disease (NTM-PD). Solitary nodules of NTM-PD around the staple line are difficult to distinguish from lung cancer. There is no clear identification from laboratory data and radiologic findings without histological examination. In the present case, we misdiagnosed the pulmonary granulomas with Mycobacterium avium complex pulmonary disease (MAC-PD) as a recurrence of lung cancer. We conducted radiation therapy. The pulmonary granulomas with MAC-PD were exacerbated by irradiation. The effects of radiation therapy for MAC-PD are unknown. When radiation therapy is performed for the patient coexistence with MAC-PD, we should pay attention to exacerbation of MAC-PD.

Clinicopathological features of lung adenocarcinoma with KRAS mutations.

BACKGROUND: KRAS and epidermal growth factor receptor (EGFR) mutations are thought to play an important role in the carcinogenesis of lung adenocarcinoma. However, clinicopathological findings of KRAS mutated adenocarcinoma cases have not yet been fully clarified. The authors analyzed the relationship between the KRAS mutation and corresponding clinicopathological findings, focusing on nonmucinous and mucinous bronchioloalveolar elements. METHODS: EGFR and KRAS mutations were detected in DNA samples extracted from 182 surgically resected tissues of lung adenocarcinomas by the Smart Amplification Process. The relations between gene mutation status and clinicopathological features were analyzed. All adenocarcinoma cases were divided into bronchioloalveolar carcinoma (BAC), adenocarcinoma with bronchioloalveolar features, and adenocarcinoma without BAC components (non-BAC). BAC/adenocarcinoma with bronchioloalveolar features tumors were further assessed for the presence of mucinous features. RESULTS: EGFR and KRAS mutations were found in 76 and 30 cases, respectively. In the KRAS mutant group, BAC/adenocarcinoma with bronchioloalveolar features was found in 22 cases, which included 10 nonmucinous and 12 mucinous tumors. Of 19 cases with mucinous BAC/adenocarcinoma with bronchioloalveolar features, KRAS mutations were detected in 12, but no EGFR mutation was detected. In the KRAS mutant group, BAC/adenocarcinoma with bronchioloalveolar features had significantly earlier pathological stages and more favorable prognoses than did non-BAC. Mucinous BAC/adenocarcinoma with bronchioloalveolar features showed less smoking history than did nonmucinous BAC/adenocarcinoma with bronchioloalveolar features and non-BAC. Furthermore, transversion type KRAS mutations were more common in non-BAC. CONCLUSIONS: KRAS mutated adenocarcinomas can be divided into BAC/adenocarcinoma with bronchioloalveolar features and non-BAC types. Non-BAC adenocarcinoma is related to smoking history and has a poor prognosis. BAC/adenocarcinoma with bronchioloalveolar features adenocarcinoma, however, has a more favorable prognosis, and mucinous BAC/adenocarcinoma with bronchioloalveolar features has little relationship to smoking history.

[High-grade fetal adenocarcinoma of the lung; report of a case].

82-year-old man was admitted with an abnormal shadow on the chest roentgenogram. Computed tomography showed a 2.8 x 2.4 cm solid tumor in S3 of the left lung. Transbronchial lung biopsy revealed adenocarcinoma and a left upper lobectomy (ND2a-1) was performed. The tumor consisted mainly of tall columnar clear cells, and no morules were found. Immunohistochemically, the tumor was positive for alpha-fetoprotein (AFP) and p53. Accordingly, we made the histological diagnosis of high-grade fetal adenocarcinoma of the lung, pT2N0M0, stage IB. The patient was not received adjuvant therapy and has been doing well without any tumor recurrence for 3 months postoperatively.

An aberrant mediastinal medial basal segmental pulmonary artery (A7a) in a patient with lung cancer: a case report.

BACKGROUND: Mediastinal branching of the A7a from the right main pulmonary artery (PA) is extremely rare. Herein, we report a patient with an aberrant mediastinal A7a who underwent right basal segmentectomy for lung cancer. CASE PRESENTATION: A 73-year-old man was referred to our department for a right lower lobe nodule measuring 18 mm in diameter on computed tomography (CT). Three-dimensional (3D) CT revealed mediastinal A7a branching from the right main PA. As the patient had undergone colectomy for advanced ascending colon cancer, the nodule was suspected to be a metastasis from the colon primary, and thus, basal segmentectomy of the right lung was performed. Intraoperatively, the A7a was observed behind the V4+5 and middle lobe bronchus. The pathological diagnosis was combined small cell carcinoma with an adenocarcinoma component (p-T1cN0M0, stage IA3). The patient subsequently received adjuvant chemotherapy for colon cancer. At 1-year postoperative follow-up, there was no evidence of disease. CONCLUSION: This is the first report describing an aberrant mediastinal A7a branching from the right main PA. It is important to obtain accurate information about variations of the PA using 3D-CT for safe anatomical pulmonary resection.

Pulmonary arteriovenous malformation with metal allergy.

We present a rare case of single pulmonary arteriovenous malformation (PAVM) with multiple metal allergies, including for platinum. A 47-year-old woman presented to our hospital without any symptoms. Enhanced computed tomography showed a single PAVM in S6 of the right lung. Interviews prompted us to suspect a history of palmoplantar pustulosis associated with metal dental filling. Dermatology patch tests for metal allergy were positive for platinum, cobalt, tin and potassium dichromate. The first choice of treatment for PAVM is endovascular treatment using a metal coil. Since the coil is composed of platinum alloy, we performed partial lung resection for PAVM without metal implants. Although metal allergy is rare for endovascular treatment, it causes an additional stress of removal of causative metal or long-term steroidal treatment. Therefore, for single PAVM with multiple metal allergies to the implants, surgical treatment without metal implants should be considered.

An aberrant medial basal segmental pulmonary artery (A7b) behind the superior segmental pulmonary vein (V6) in a patient undergoing right superior segment (S6) segmentectomy.

Herein, we report the first case of a patient with lung cancer with an aberrant medial basal segmental pulmonary artery (A7b) behind the superior segmental pulmonary vein (V6) who underwent right superior segment (S6) segmentectomy via uniportal video-assisted thoracoscopic surgery (uVATS). A 56-year-old man with a right lower lobe pure ground-glass nodule (GGN), measuring 12 mm in diameter on computed tomography (CT) had an aberrant A7b branching from the basal pulmonary artery, which was located behind the V6 as detected on 3D CT. The right S6 segmentectomy, via uVATS, for the GGN was performed. The postoperative course was uneventful. The final pathological diagnosis was invasive adenocarcinoma (p-T1bN0M0, stage IA2) with no evidence of disease recurrence at 3-month follow-up. Thoracic surgeons should be aware of the possibility of damaging the A7b when dividing the V6 for S6 segmentectomy, especially during uVATS because of insufficient dorsal visibility.

Comprehensive expressional analysis of chemosensitivity-related markers in large cell neuroendocrine carcinoma of the lung.

OBJECTIVES: Various drug-sensitivity markers have been reported to be associated with tumor progression and chemotherapy resistance. Detailed expression profiles of sensitivity markers for cytotoxic chemotherapy in pulmonary large cell neuroendocrine carcinoma (LCNEC) remain unclear. Herein, we aimed to clarify the correlation between the expression of drug-sensitivity markers and clinicopathological features, prognostic impact, and status of tumor immunity in patients with LCNEC. METHODS: We retrospectively analyzed the correlation between clinicopathological features and the expression of drug-sensitivity-related markers, including vascular endothelial growth factor 2 (VEGFR2), thymidylate synthase (TS), tubulin beta 3 class III (TUBB3), topoisomerase I (Topo-I), and Topo-II in 92 surgically resected LCNEC samples. Furthermore, we examined the prognostic significance of expression of these and their correlation with the immune cell status. RESULTS: Overall, high expression of TS, TUBB3, VEGFR2, Topo-I, and Topo-II was detected in 50 (54%), 31 (34%), 23 (25%), 65 (71%), and 36 (39%) samples, respectively. Univariate and multivariate analyses revealed that advanced pathological T and N factors, positive lymphatic permeation, and Topo-II expression were independent unfavorable prognosticators for recurrence-free survival, and advanced pathological T and N factors, Topo-II positive expression, and TS positive expression were independent unfavorable prognosticators for overall survival. In terms of correlation with immune cell status, higher expression of VEGFR2 was closely linked to negative PD-L1 expression. CONCLUSIONS: These findings suggest that elevated Topo-II and TS expression may contribute to poor outcomes through protumoral biology in patients with LCNEC, and elevated VEGFR2 expression might negatively impact tumor immune reactions in LCNEC.

[Surgical treatment and outcome for postoperative recurrent or second primary lung cancer].

From 2000 to 2009, we retrospectively reviewed 62 patients who underwent surgical treatment for postoperative recurrent or 2nd primary lung cancer. Of the 62 patients, 43 were men and 19 were women with an average age of 67.6 years old. The histology of the initial primary lung cancer was adenocarcinoma in 42 patients, squamous cell carcinoma in 18, large cell carcinoma in 1 and small cell carcinoma in 1. The surgical procedures for 1st operation were lobectomy with mediastinal lymph node dissection in 52, bilobectomy with mediastinal lymph node dissection in 4, sleeve lobectomy with mediastinal lymph node dissection in 3, and lobectomy + segmentectomy or wedge resection with mediastinal lymph node dissection in 3. p-stage of the 1st primary lung cancer was IA in 22, IB in 16, II A in 7, IIB in 6, IIIA in 6, IIIB in 4, and IV in 1. On the 2nd operation, 56 patients underwent limited surgery. Five patients underwent a lobectomy twice metachronous bilateral lesions and 1 patient underwent completion pneumonectomy (CP) at the 2nd operation. The average age at 2nd operation was 71.8 years old. Of these, 42 patients were diagnosed 2nd primary lung cancer, 20 patients were recurrent disease histologically. The 5-year survival rate of the patients with metachronous and recurrent disease from the 2nd operation was 54.1%, and 43.1%, respectively. Although lobectomy or CP should be considered the surgical procedure of choice for patients with metachronous lung cancer, with this result, we consider that postoperative good survival can be expected by even the limited operation for cases of postoperative recurrent or 2nd primary lung cancer because of possible early detection. We conclude that limited surgery may be a treatment of choice for recurrent or 2nd primary lung cancer after initial operation.

Spontaneous pneumothorax in a patient with multiple pulmonary arteriovenous malformations caused by hereditary hemorrhagic telangiectasia: a case report.

Spontaneous pneumothorax occurring in patients with pulmonary arteriovenous malformations (PAVMs) caused by hereditary hemorrhagic telangiectasia (HHT) is extremely rare. We report a case of spontaneous pneumothorax in a PAVM patient. A 26-year-old man with previously diagnosed HHT and multiple small PAVMs presented with chest pain and dyspnea and was referred to our hospital. Chest X-ray showed a left-sided pneumothorax. Computed tomography (CT) showed apical bullae on both sides of the upper lobe. We clarified the location of PAVMs by 3D-CT to avoid the massive bleeding caused by careless grasping of PAVMs and unintentional incomplete resection of the PAVMs during the pneumothorax surgery. Considering the risk of exacerbation, the patient underwent bullectomy of the left upper lobe. The postoperative histopathological examination indicated that the pneumothorax occurred spontaneously in the HHT patient. We should clarify the location of PAVMs to avoid bleeding caused by the grasping of PAVMs during surgery.

Prognostic Significance of Tumor Immunity in Surgically Resected Pulmonary Pleomorphic Carcinoma.

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare aggressive neoplasm, with dismal prognosis. Whether tumor immunity is associated with the progressive biological behavior of PPC remains unclear. The purpose of this study was to examine the prognostic significance of tumor immunity-related markers such as programmed death-1 ligand (PD-L1) and CD4+ or CD8+ tumor-infiltrating lymphocytes (TILs) in patients with surgically resected PPC. PATIENTS AND METHODS: Ninety-nine patients with surgically resected PPC were assessed by immunohistochemistry. The expression of PD-L1, CD4, and CD8 was examined in specimens of the resected tumors. RESULTS: PD-L1 was highly expressed in 61% (60/99) of lesions and high expression of CD4 and CD8 was identified in 42% (42/99) and 51% (51/99) of lesions, respectively. There was no relationship between the expression PD-L1 and the numbers of CD4+ or CD8+ TILs. The expression of PD-L1 was not identified as a significant prognostic marker; however, a low number of CD4+ TILs was identified as an independent marker for predicting a worse outcome after surgical resection of PPC, especially in patients with an epithelial component of adenocarcinoma or early stage of disease. By univariate analysis, a low number of CD8+ TILs was found to be a significant prognostic marker linked to poor overall survival in patients with non-adenocarcinoma components. CONCLUSION: A low number of CD4+ TILs is an independent marker for predicting a favorable prognosis after surgical resection in patients with PPC, especially in patients with adenocarcinoma components or early stage of disease.

Impact of somatic mutations on prognosis in resected non-small-cell lung cancer: The Japan Molecular Epidemiology for lung cancer study.

BACKGROUND: To report the follow up data and clinical outcomes of the JME study (UMIN 000008177), a prospective, multicenter, molecular epidemiology examination of 876 surgically resected non-small-cell lung cancer (NSCLC) cases, and the impact of somatic mutations (72 cancer-associated genes) on recurrence-free survival (RFS) and overall survival (OS). METHODS: Patients were enrolled between July 2012 and December 2013, with follow up to 30th November 2017. A Cox proportional hazards model was used to assess the impact of gene mutations on RFS and OS, considering sex, smoking history, age, stage, histology, EGFR, KRAS, TP53, and number of coexisting mutations. RESULTS: Of 876 patients, 172 had ≥2 somatic mutations. Median follow-up was 48.4 months. On multivariate analysis, number of coexisting mutations (≥2 vs 0 or 1, HR = 2.012, 95% CI: 1.488-2.695), age (≥70 vs <70 years, HR = 1.583, 95% CI: 1.229-2.049), gender (male vs female, HR = 1.503, 95% CI: 1.045-2.170) and pathological stage (II vs I, HR = 3.386, 95% CI: 2.447-4.646; ≥III vs I, HR = 6.307, 95% CI: 4.680-8.476) were significantly associated with RFS, while EGFR mutation (yes vs no, HR = 0.482, 95% CI: 0.309-0.736), number of coexisting mutations (≥2 vs 0 or 1, HR = 1.695, 95% CI: 1.143-2.467), age (≥70 vs <70 years, HR = 1.932, 95% CI: 1.385-2.726), and pathological stage (II vs I, HR = 2.209, 95% CI: 1.431-3.347; ≥III vs I, HR = 5.286, 95% CI: 3.682-7.566) were also significant for OS. CONCLUSION: A smaller number of coexisting mutations, earlier stage, and younger age were associated with longer RFS and OS, while EGFR mutations were significantly associated with improved OS.

CD98 expression is associated with poor prognosis in resected non-small-cell lung cancer with lymph node metastases.

BACKGROUND: The purpose of this study was to evaluate the prognostic value of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in resectable non-small-cell lung cancer (NSCLC) patients with N1 and N2 nodal involvement. METHODS: A total of 220 consecutive patients were retrospectively reviewed. Immunohistochemical expression of LAT1, CD98, Ki-67 labeling index, vascular endothelial growth factor (VEGF), and microvessel density (MVD) was correlated with clinical features and prognosis of patients after complete resection of the tumor. RESULTS: Positive expression of LAT1 and CD98 was recognized in 60% (132/220) and 47% (103/220), respectively (P = 0.021). A positive rate of LAT1 expression was significantly higher in squamous cell carcinoma (SQC) (91%; 65/71) and large cell carcinoma (LCC) (82%; 9/11) than in adenocarcinoma (AC) (42%; 58/138). Moreover, a positive rate of CD98 expression was also significantly higher in SQC (76%; 54/71) and LCC (73%; 8/11) than in AC (30%; 42/138). LAT1 expression was significantly correlated with CD98, Ki-67 labeling index, VEGF, and MVD. The 5-year survival rates of LAT1-positive and LAT1-negative patients and CD98-positive and CD98-negative patients, were 43% and 48% (P = 0.1043), respectively and 39% and 50% (P = 0.0239), respectively. Multivariate analysis confirmed that positive expression of CD98 was an independent factor for predicting a poor prognosis. CONCLUSIONS: In our limited series, CD98 is a pathological factor that predicts prognosis in resectable adenocarcinoma patients with N2 disease.

High-grade neuroendocrine carcinoma of the lung: comparative clinicopathological study of large cell neuroendocrine carcinoma and small cell lung carcinoma.

Large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) are high-grade neuroendocrine carcinomas. In order to clarify the similarities and differences between these cancers, 22 cases each of LCNEC and SCLC were collected and a comparative pathological study was carried out. First, their clinicopathological characteristics were confirmed, which were very similar to those previously reported. The 5 year survival rate of LCNEC and SCLC patients was 38.3% and 29.7%, respectively. The morphological characteristics of LCNEC and SCLC were then reviewed with regard to the morphology previously used to differentiate these cancers. As a result, many morphological indicators, such as tumor cell size, nuclear/cytoplasmic ratio, nuclear molding, rosette formation, prominent nucleoli and karyolysis were confirmed to be significant indicators for distinguishing LCNEC from SCLC. On comparative immunohistochemistry, LCNEC had significantly high staining scores for the expression of keratin 7 and 18, E- and P-cadherins, beta-catenin, villin 1, retinoblastoma protein (pRB), c-met and alpha-enolase. These results might reflect the differentiation or deviation of LCNEC toward an epithelial nature irrespective of neuroendocrine tumor lineage. In conclusion, the present comparative study of LCNEC and SCLC defined the similarities and differences between these cancers, and showed the biologically and clinicopathologically overlapping spectrum of the tumor lineage.

Prognostic Impact of ß2 Adrenergic Receptor Expression in Surgically Resected Pulmonary Pleomorphic Carcinoma.

BACKGROUND/AIM: The ß2-adrenergic receptor (ß2AR) is highly expressed in various human cancers and has been linked to tumor growth and metastases. Although ß2AR is considered a novel therapeutic target of human neoplasms, the clinicopathological significance of ß2AR expression in patients with pulmonary pleomorphic carcinoma (PPC) remains unclear. The aim of this study was to clarify the prognostic impact of ß2AR in PPC. PATIENTS AND METHODS: One hundred and five Japanese patients with surgically resected PPC were included in the study. The expression levels of ß2AR were assessed by immunohistochemistry in specimens from the resected tumors, and their association with patient survival, as well as with tumor characteristics was investigated. RESULTS: ß2AR was highly expressed in 63% of all patients, irrespective of adenocarcinoma components present. The ß2AR expression was significantly associated with lymph node metastasis, lymphatic permeation and tumor cell proliferation in PPC patients with early-stage disease (stage I or II). A high ß2AR expression was identified as a significant predictor of worse prognosis for PPC patients during early stages of the disease. Multivariate analysis confirmed that ß2AR expression was an independent factor for predicting the overall survival of PPC patients. CONCLUSION: ß2AR can serve as a significant predictor of tumor aggressiveness and poor survival for PPC patients, especially those with early-stage disease.

Clinical Significance of Various Drug-Sensitivity Markers in Patients with Surgically Resected Pulmonary Pleomorphic Carcinoma.

Various drug-sensitivity markers are potentially responsible for tumor progression and chemotherapy resistance in cancer patients with both epithelial and sarcomatous components; however, the clinicopathological significance of drug-sensitivity markers in patients with pulmonary pleomorphic carcinoma (PPC) remains unknown. Here, we clarified the prognostic impact of these drug-sensitivity markers in PPC by performing immunohistochemical and clinicopathologic analyses of samples from 105 patients with surgically resected PPC in order to evaluate levels of vascular endothelial growth factor 2 (VEGFR2), stathmin 1 (STMN1), tubulin ß3 class III (TUBB3), thymidylate synthetase (TS), topoisomerase II (Topo-II), glucose-regulated protein, and 78 kDa (GRP78)/binding immunoglobulin protein (BiP). We observed the rates of high expression for VEGFR2, STMN1, TUBB3, TS, Topo-II, and GRP78/BiP were 33% (39/105), 35% (37/105), 61% (64/105), 51% (53/105), 31% (33/105), and 51% (53/105) of the samples, respectively. Moreover, multivariate analysis identified VEGFR2 and GRP78/BiP as significant independent markers for predicting worse prognosis. These findings suggested elevated VEGFR2 and decreased GRP78/BiP levels as independent factors for predicting poor outcomes following surgical resection in patients with PPC.

Expression of amino acid transporter (LAT1 and 4F2hc) in pulmonary pleomorphic carcinoma.

Amino acid transporters are necessary for tumor growth, metastasis, and survival of various neoplasms; however, the clinicopathological significance of L-type amino acid transporter 1 (LAT1) and 4F2 cell surface antigen (4F2hc) in patients with pulmonary pleomorphic carcinoma (PPC) remainsunknown. The aim of this study is to clarify the prognostic impact of these amino acid transporters in PPC. One hundred five patients with surgically resected PPC were assessed by immunohistochemistry. The expression of LAT1 and 4F2hc, and Ki-67 labeling index were investigated using specimens of the resected tumors. LAT1 and 4F2hc were highly expressed in 35% and 53% of all patients (n = 105, P < .01), 25% and 48% of patients with an adenocarcinoma component (n = 48, P = .02), and 44% and 58% of patients with a nonadenocarcinoma component (n = 57, P = .18), respectively. A high LAT1 expression was significantly related to advanced disease, lymphatic permeation, tumor cell proliferation, and 4F2hc expression. By multivariate analysis, LAT1 and 4F2hc were identified as significant independent markers for predicting a worse prognosis. LAT1 is highly expressed in PPC, and high LAT1 expression can serve as a significant predictor linked to a worse prognosis in patients with PPC.

Expression of L-type amino acid transporter 1 (LAT1) in neuroendocrine tumors of the lung.

Amino acid transport systems play an important role in cellular proliferation. L-type amino acid transporter 1 (LAT1) has been associated with tumor growth, and is highly expressed in the established tumor cell lines and primary human neoplasms. In this study, we investigated the expression of LAT1 to evaluate the malignant potential and prognostic significance in neuroendocrine (NE) tumors of the lung. Twenty-one surgically resected, large cell neuroendocrine carcinomas (LCNEC), 13 small cell lung cancers (SCLC), five atypical carcinoids (AC), and 10 typical carcinoids (TC) were enrolled in the study. LAT1 expression and Ki-67 labeling index of the NE tumors were analyzed by immunohistochemical staining. LAT1 was overexpressed in 52.4% of the LCNEC, in 46.2% of the SCLC, and in 25% of the AC. LAT1 expression in LCNEC was significantly associated with lymph node metastasis and poor outcome. Moreover, a significant correlation was found between LAT1 expression and Ki-67 in both LCNEC and SCLC. Expression of LAT1 tended to increase from low-grade to high-grade NE tumors. The present results suggest that LAT1 may play a significant role in cellular proliferation, lymph node metastasis, and poor outcome in patients with NE tumors of the lung.