Jun Moriya

Cyclin D1, p16 and retinoblastoma gene product expression as a predictor for prognosis in non-small cell lung cancer at stages I and II

The association of the immunohistochemical expressions of cyclin D1, p16 and the retinoblastoma gene product (pRB) with the prognoses of 106 patients with non-small cell lung cancer (NSCLC) at stages I and II after a complete resection was investigated. We used antibodies recognizing nuclear and cytoplasmic cyclin D1, p16 and pRB. In 106 tumors, the positive rates of cyclin D1, p16 and pRB were 46, 54 and 48%, respectively. Cyclin D1-positive (cyclin D1(+)) patients had significantly poorer survival prognoses than cyclin D1-negative (cyclin D1(-)) patients (log-rank test, P=0.0002; Wilcoxon test, P=0.0005), whereas p16-positive (p16(+)) patients had significantly better prognoses than p16-negative (p16(-)) patients (log-rank test, P=0.0063; Wilcoxon test, P=0.0044). The survival period was over 65% for patients with cyclin D1(-)/p16(+) (n=34) at 120 months after surgery, whereas patients with cyclin D1(+)/p16(-) patients (n=22) had a 50% survival period at 49 months. The cumulative survival rate of cyclin D1(+)/p16(-) patients was significantly lower than that of cyclin D1(-)/p16(+) patients (log-rank test, P=0.0004; Wilcoxon test, P=0.0002). The pRB did not influence significantly the survival rate. Our results indicate that cyclin D1 and p16, especially a combination of cyclin D1 and p16, are very useful to predict the prognosis of patient with NSCLC after curative resection independent of pathological stages I and II.

Clinicopathological analysis of early-stage gastric cancers detected after successful eradication of Helicobacter pylori.

Background and Aims:  The results of a randomized controlled study and meta‐analysis study have recently proved that Helicobacter pylori eradication has a preventive effect against the development of metachronous and primary gastric cancer. However, gastric cancer is sometimes detected after successful eradication. There is a lack of study about gastric cancers in eradicated patients. To clarify the characteristics of gastric cancers detected after H. pylori eradication, we analyzed the clinicopathological features of these cancers.

Adenoma with clear cell change of the large intestine

Background and Objectives: Clear cell change of the large intestinal neoplasm is rare, and its character remains unclear. We report a case of the large intestinal adenoma with clear cell change with immunohistochemical and molecular studies to investigate whether the clear cell change is associated with a malignant progression of the adenoma.

Cyclin D1 gene amplification in esophageal carcinosarcoma shown by differential polymerase chain reaction

We studied cyclin D1 gene amplification in four esophageal carcinosarcomas using the differential polymerase chain reaction. Three cases showed amplification in the sarcomatous components, and one of these also showed amplification in the carcinomatous component. No amplification was detected in the other case. We also examined p53 expression in these four tumors by immunostaining. Both components of all four cases showed diffuse overexpression of p53 protein in the nuclei. Our results showed that the cyclin D1 gene is frequently amplified in esophageal carcinosarcoma, especially in the sarcomatous component. Two cases showed amplification only in the sarcomatous component, suggesting that amplification may have a role in the pathogenesis of that component of this malignancy. The diffuse overexpression of p53 observed in both components suggests that such overexpression, which could be the result of somatic mutation, might be an early event in the pathogenesis of esophageal carcinosarcoma.

Inverted papilloma of the nasal cavity presenting with massive amounts of squamous metaplastic cells in sputum. A case report.

BACKGROUND Squamous metaplasic cells are rarely seen in sputum of female nonsmokers. CASE A 47-year-old female nonsmoker presented with massive amounts of squamous metaplasic cells in sputum and an elevated level of squamous cell carcinoma (SCC) antigen in serum present for months, while no causative lesion was detected either by lung computed tomography or bronchoscopy. The patient was eventually diagnosed as having inverted papilloma in the right nasal cavity. Resection of the tumor brought about disappearance of squamous metaplastic cells in sputum and return of serum SCC antigen to the normal range. CONCLUSION This case clearly demonstrates that squamous metaplastic cells in sputum can originate in lesions in the nasal cavity, although they are rare. It should be kept in mind that the nasal cavity is a potential site producing squamous metaplastic cells in sputum.

Abstract 4118: Expression of CD133 as a prognostic marker of non-small cell lung cancers

[Background] CD133 is a membrance glycoprotein with five transmembrance loops. Previous reports have suggested that CD133-positive subpopulation of multipotent cells with extensive proliferative and self-renewal abilities has biological features as a cancer stem cell. In addition, it has been reported that the presence of CD133-positive cells was associated with a significantly poorer prognosis compared with the CD133-negative cells in some solid tumors, including colon cancer, hepatocellular carcinoma and glioma. However, little is known about the relationship between the expression of CD133 and clinical and clinicopathological characteristics in lung cancer. [Aim and Method] We conducted immunohistochemical assessment of 161 surgically resected non-small cell lung cancers (NSCLCs) at Hokkaido University Hospital between 1982 and 1994 to evaluate the correlation between CD133 expression and various features, including clinical and clinicopathological characteristics. [Results] Normal alveoli were used as negative controls and Bowman9s capsule basement membrane as positive controls. CD133 expression was significantly correlated with advanced p-Stage (p=0.040). The Kaplan-Meier method demonstrated that NSCLC patients with CD133 expression in tumor cells showed poor prognosis compared to those without CD133 expression in p-Stage II, III and IV (p=0.0098). CD133 expression alone was an independent factor for unfavorable prognostic in those patients (Hazard Ratio=3.157, p=0.015). [Conclusion] CD133 expression was correlated with p-Stage and was an independent factor for unfavorable prognosis in patients with p-Stage II, III and IV NSCLCs. CD133 expression may be a novel prognostic marker for NSCLCs. 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 4118. doi:10.1158/1538-7445.AM2011-4118

P-136 Establishment and characterization of amylase-producing lung adenocarcinoma cell line, IMEC-2

BACKGROUND Few studies have successfully established an amylase-producing lung cancer cell line or have examined its cytological, biochemical and biological features. PATIENTS AND METHODS Cancer cells, isolated from pleural effusion using a gradient method, were cultivated. RESULTS Amylase production from the newly established cell line was confirmed by positive staining for alpha-amylase and increased amylase levels in the culture supernatant. Electron microscopy revealed zymogen granule-like structures. Sialylation of salivary-type amylase was confirmed directly from the cell line by examining the neuraminidase sensitivity and amylase elution profile under high-performance liquid chromatography. Neither EGFR or KRAS mutation were found. CONCLUSION This cell line offers a useful tool for analyzing the pathogenesis and pathophysiology of amylase-producing lung cancers. Moreover, it might be useful for probing the metastasis and invasiveness of lung cancer cells and for developing an early diagnostic method based on sialylated salivary-amylase production.