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.

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.

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.

The Effects of Components of Grazing System on Welfare of Fattening Pigs.

The objective of this study was to clarify the most effective component of grazing for improving welfare of fattening pigs. This study compared welfare indicators of 20 fattening pigs aged 100 to 124 days (the prior period) and 138 to 164 days (the latter period) in an indoor housing system (IS), an outdoor pasturing system (OP), a concrete floor paddock system (CF), a concrete floor paddock system with fresh grass (FG), or a soil floor paddock system (SF). The last three treatments include important components of a grazing system: extra space, grass feed, and soil floor. Behavior, wounds on the body, and performances, measured as average daily gain (ADG) and feed conversion ratio, were observed. CF pigs behaved similarly to IS pigs. FG pigs showed higher levels of foraging, chewing and activity. SF pigs engaged in higher levels of foraging, exploring, activity, and rooting, and showed a similar amount of playing behavior as OP pigs. ADG was the same in all treatments at the prior period, and increased in the order FG, IS, CF, SF, and OP at the latter. The behaviors and performance of SF pigs resembled those of OP which seemed to indicate a consistently higher standard of welfare than the other treatments. In conclusion, the existence of a soil floor is the most important component of a pasture for improving the welfare of pigs.

Effect of Suckling Systems on Serum Oxytocin and Cortisol Concentrations and Behavior to a Novel Object in Beef Calves.

We investigated differences between effects of natural- and bucket-suckling methods on basal serum oxytocin (OT) and cortisol concentrations, and the effect of OT concentration on affiliative and investigative behavior of calves to a novel object. Ten Japanese Black calves, balanced with birth order, were allocated evenly to natural-suckling (NS) and bucket suckling (BS) groups. Blood samples were collected at the ages of 1 and 2 months (1 week after weaning) calves, and serum OT and cortisol concentrations were measured using enzyme-linked immunosorbent assay and enzymeimmunoassay tests, respectively. Each calf at the age of 2 months (2 weeks after weaning) was released into an open-field with a calf decoy, and its investigative and affiliative behaviors were recorded for 20 minutes. In 1-month-old calves, the basal serum OT concentration (25.5±4.9 [mean±standard deviation, pg/mL]) of NS was significantly higher than that of BS (16.9±6.7) (p<0.05), whereas the basal cortisol concentration (5.8±2.5 [mean±standard deviation, ng/mL]) of NS was significantly lower than that in BS (10.0±2.8) (p<0.05). Additionally, a negative correlation was noted between serum OT and cortisol concentrations in 1-month-old calves (p = 0.06). Further, the higher serum OT concentration the calves had at 1 month old, the more investigative the calves were at 2 months old but not affiliative in the open-field with a calf decoy. Thus, we concluded that the natural suckling method from a dam elevates the basal serum OT concentration in calves, and high serum OT concentrations induce investigative behavior and attenuate cortisol concentrations.

Individual difference in serum oxytocin concentrations of calves and the correlation with those in dams.

We examined individual differences in serum oxytocin concentrations (OT) of calves, and assessed whether these differences were correlated with their dams' milk and serum OT. Eight Holstein (H), nine Japanese Shorthorn (JS), and six Japanese Black (JB) calves were examined. Blood was collected three times during the first month in H calves, while their dams' blood was collected three times prior to parturition. Milk was collected twice after parturition from H cows. Blood from JS and JB calves were collected at 1 and 4 months old, while of their dams only once before parturition. Serum OT in H calves at 7 days old was significantly correlated with that at 30 days. Serum OT of JS calves at 1 month old was significantly correlated to that at 4 months, while of JB calves was also positively correlated (r = 0.70). Serum OT of calves showed significant individual differences in each breed. Serum OT of calves was not correlated with the milk OT of dams, except for 3-day-old calves that fed on their dams' milk. We concluded that although serum OT differed among individuals, this difference was stable within each individual and not affected by the serum OT of the dams.

Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer.

PURPOSE: It has been reported that the mutations of epidermal growth factor receptor (EGFR) are detected in lung cancers. Studies of EGFR mutations in large numbers of patients' tumors with clinical data including response to EGFR tyrosine kinase directed therapy are needed to develop a robust database for clinical use. The purpose of the present study is to gain further insights into the significance of EGFR mutation in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: We investigated the clinicopathologic significance of tyrosine kinase domain (exons 18-21) EGFR mutations in 120 patients with primary NSCLC and the correlation between EGFR mutation and sensitivity to gefitinib in an additional 20 NSCLC patients treated with gefitinib. In addition, onocogenic KRAS mutations and RASSF1A promoter methylation were determined in the same samples. RESULTS: EGFR mutation was detected in 29 of 120 (24%) tumors. All of the 29 (40%) mutations occurred in 72 adenocarcinomas. EGFR mutation was significantly more frequent in females (47%) than males (12%, P < 0.0001), in younger patients (38%) than older patients (10%, P = 0.0005), in nonsmokers (47%) than smokers (13%, P < 0.0001), and in well-differentiated tumors (39%) than moderately and poorly differentiated tumors (7%, P < 0.0001). Mutation of the EGFR gene was preferentially observed in advanced disease. Furthermore, EGFR mutations were detected in 11 of 14 (79%) responders, whereas none of six (0%) nonresponders had the mutation (P = 0.0022). CONCLUSIONS: These results in Japanese (East Asian) patients indicated that EGFR mutation plays an important role in pathogenesis of lung adenocarcinoma.