Tadahiro Nozoe

Association Between Estrogen Receptor-{beta} Expression and Epidermal Growth Factor Receptor Mutation in the Postoperative Prognosis of Adenocarcinoma of the Lung

PURPOSE Adenocarcinoma of the lung unrelated to a smoking habit occurs more frequently in women than men, thus suggesting an association between female hormones and development of these tumors. The aim of this study was to elucidate the correlation between expression of estrogen receptor (ER) and clinicopathologic factors, including a mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR), and prognosis in adenocarcinoma of the lung. PATIENTS AND METHODS This study evaluated 447 resected primary lung adenocarcinoma specimens. The expression of ERalpha and ERbeta was evaluated with an immunohistochemical method. The EGFR mutation was evaluated with polymerase chain reaction. RESULTS A strong cytoplasmic expression of ERalpha and nuclear expression of ERbeta were detected in 49.4% and 48.5% of all patients, respectively. A strong nuclear expression of ERbeta was independently associated with the EGFR mutations (odds ratio = 2.947; 95% CI, 1.97 to 4.57; P < .001) and good differentiation (odds ratio = 1.84; 95% CI, 1.21 to 2.80; P = .004) and was correlated with an increasing disease-free survival in patients with EGFR mutations (hazard ratio = 2.18; 95% CI, 1.18 to 4.06; P = .014). However, no prognostic significance was identified in patients without EGFR mutations. No clinicopathologic and/or prognostic significance of a strong expression of cytoplasmic ERalpha was found. CONCLUSION A strong nuclear expression of ERbeta correlates with EGFR mutations, and its favorable prognostic significance was influenced by the EGFR mutations in adenocarcinoma of the lung.

Gender Difference as a Prognostic Factor in Patients Undergoing Resection of Non-Small Cell Lung Cancer

PurposeWe studied the effects of gender difference on the incidence of lung cancer and its mortality rate, which is a subject of much discussion.MethodsWe examined gender difference in the clinical features of 491 men and 222 women who underwent resection of primary non-small cell lung cancer (NSCLC) between 1994 and 2004.ResultsThe histological types of cancer were adenocarcinoma in 249 (51%) of the men and 182 (82%) of the women, and squamous cell carcinoma in 182 (37%) of the men and 27 (12%) of the women. The incidence of adenocarcinoma was significantly higher in the women. The proportion of stage IA disease was significantly higher in the women than in the men (45% vs 29%, respectively). The 5-year overall survival rates were 50% in the men and 63% in the women. In a multivariate analysis, gender difference was an independent prognostic factor; however, when death as a result of unrelated disease was excluded, there was no significant difference in prognosis.ConclusionAlthough the higher incidences of adenocarcinoma and stage IA cancer contributed to the good results of surgery in women, the low incidence of death attributed to diseases other than lung cancer was a major reason for their better prognosis.

Expression of cytochrome P450 in non-small cell lung cancer.

Lung cancer accounts for most of cancer-related deaths in both men and women. Lung cancer is also associated with cigarette smoking that exposes the individual to carcinogenic chemicals. Normally, CYP enzymes (cytochrome P450s) metabolize carcinogens to inactive derivatives, however, occasionally the action of CYP enzymes leads to development of more potent carcinogens. In addition to the metabolism of carcinogenic compounds, CYP enzymes are also involved in the activation and/or inactivation of agents, which are used in the treatment of lung cancer. Therefore, the local level of CYP enzymes in lung cancer and surrounding tissues could be an important determinant in the efficacy of anticancer drugs. Furthermore, the expression of CYP19 (aromatase), estrogen synthesis P450, was found in more than 80 percent of non-small cell lung cancers. Lung cancer was also found to frequently express CYP24A1 that converts 1 alpha, 25-dihydroxyvitamin D3 to its inactive 24-hydroxylated derivatives. The understanding of the local expression of CYP enzymes in tumor tissues is important in the development of better treatment for lung cancer and a standardized treatment, tailor-made, for individual patients.

Significance of Immunohistochemical Expression of p27 and Involucrin as the Marker of Cellular Differentiation of Squamous Cell Carcinoma of the Esophagus

Purpose: p27kip1 belongs to the KIP/CIP family of cyclin-dependent kinase inhibitors and is considered to be a tumor suppressor. Involucrin has been known as a marker of differentiation of squamous cell carcinoma (SCC). The aim of this study was to evaluate the clinicopathologic significance of the expression of p27 and involucrin in esophageal SCC. Methods: Immunohistochemical expression of p27 and involucrin was examined in 70 specimens of esophageal SCC. The correlation of the expression of these proteins and clinicopathologic features was evaluated. Results: Cellular differentiation in esophageal SCC was significantly correlated with the expression of p27 and involucrin (p = 0.010 and p = 0.002, respectively). Among well, moderately and poorly differentiated SCCs, 45.8 ± 21.6, 20.0 ± 15.0 and 10.6 ± 9.1% of carcinoma cells expressed involucrin, respectively (p < 0.0001 for well vs. poorly, p < 0.0001 for well vs. moderately, and p = 0.042 for moderately vs. poorly). There existed a more powerful statistical difference regarding the histological grade between SCCs with the expression of both p27 and involucrin and tumors with other expression patterns (p = 0.0001). Conclusions: Expression of both p27 and involucrin can be a powerful biological marker of cellular differentiation of esophageal SCC.

Increased cytochrome P450 and aryl hydrocarbon receptor in bronchial epithelium of heavy smokers with non-small cell lung carcinoma carries a poor prognosis.

Smoking induces mutations via the formation of DNA-adducts in the bronchial and alveolar epithelium and contributes to the development of lung cancer. Benz(a)pyrene and nitrosamine, typical carcinogens in cigarette smoke, undergo metabolic activation by the phase I enzymes, such as cytochrome P450 (CYP) 1A1, CYP2A6 and CYP2E1. The transcriptional regulation of these phase I enzymes is regulated by arylhydrocarbon receptor (AH-R) which binds many well-known carcinogens. To identify a cause and effect relationship, the expression of cytochrome CYP and AH-R in the bronchial epithelium was correlated with the history of cigarette smoking in patients with non-small cell lung carcinoma (NSCLC). Although CYP3A+ cells were absent in the bronchial epithelium of all patients, there were many CYP2E1+ cells in heavy (>1000 cigarette/day x year) smokers (38.5%). In contra-distinction, there was significantly less number of CYP2E1+ cells in light (less than 1000 cigarette/day x year) smokers (15.6%) or non-smokers (10.0%). Similarly, there were more CYP1A1+ (19.2%) and CYP2A6+ cells in heavy (65.4%) smokers as compared to non-smokers. The number of AH-R+ cells was also significantly higher in cases with p53 mutation (62.5%) than those without (12.2%) mutation. Since in patients with early NSCLC, CYP positivity showed a close correlation with a poor survival (p less than 0.01), expression of CYP in bronchial epithelium has a prognostic potential.

Postoperative prognosis in patients with non-small cell lung cancer according to the method of initial detection.

Introduction: In this study, we investigated the difference in the surgical results of non-small cell lung cancer according to the method of initial detection. Methods: We reviewed the medical records of 796 patients who underwent pulmonary resection for non-small cell lung cancer between 1994 and 2005. The subjects consisted of 171 patients whose cancer was detected by a medical checkup or mass health screening (group I), 316 patients who were under evaluation for other diseases or with symptoms related to other diseases (group II), and 309 patients with lung cancer–related symptoms (group III). The mean ages of the three groups were 63.2, 69.7, and 68.2 years old, respectively, with group I being significantly younger than the other groups. The proportion of women in the symptomatic group was significantly lower than that of men. Results: Pathologic stage I lung cancer was found in 112 (65.5%), 209 (65.2%), and 110 (35.6%) patients in groups I, II, and III, respectively. In comparison with stage II–IV cancer, stage I cancer was diagnosed more frequently in group I. According to the histologic type, adenocarcinoma was found in 132 patients (77.2%) in group I. However, squamous cell carcinoma was detected in only 27 patients (15.8%) in group I. The overall 5-year survival rates were 71.9%, 60.2%, and 48.0% in groups I, II, and III, respectively. Groups I and II had significantly better prognoses than group III. Conclusion: Groups I and II had favorable prognoses, and the presence of symptoms related to lung cancer was a significantly unfavorable prognostic factor independent of all other factors.

Gastro-pancreaticostomy using a tube stent as a less invasive palliative treatment for malignant obstructive pancreatitis

Surgical palliation of malignant obstructive pancreatitis poses a considerable burden to patients, especially those with extensive disease. We herein present a novel technique for performing gastro-pancreaticostomy using a tube stent as a less invasive palliative treatment for malignant obstructive pancreatitis. The main pancreatic duct was punctured via the wall of the pyloric antrum. After the insertion of a guidewire, a double pigtail-type tube stent with side holes was inserted into the main pancreatic duct through the wall of the pyloric antrum. This technique was useful as a means of accomplishing less invasive palliative treatment, and has the potential to improve the quality of life for patients with malignant obstructive pancreatitis.

Pancreatic endocrine carcinoma presenting with gastric varices derived by left-sided portal hypertension: a case report

We herein report a 71-year-old man with pancreatic carcinoma presenting as gastric varices caused by an obstruction of the splenic vein compressed by the tumor, which also invaded the spleen, stomach, transverse colon, left kidney, and left adrenal gland. A complete resection of distal pancreatomy and lymph node dissection with splenenctomy, left adrenalectomy, left nephrectomy, and partial resection of transverse colon and stomach were performed. After the resection, the gastric varices completely disappeared without any interventional therapy. The gastric varices observed in this case were considered to be derived from left-sided portal hypertension secondary to splenic vein occlusion, which is an uncommon complication mostly associated with pancreatitis and pancreatic carcinoma. Now that 17 months have passed after his operation, the patient is alive and in satisfactory condition without any signs of recurrence.