Ryo Masuda

Frequent loss of imprinting of IGF2 and MEST in lung adenocarcinoma

Genomic imprinting is a parental origin–specific chromosomal modification that causes differential expression of maternal and paternal alleles of a gene. Accumulating evidence suggests that deregulation of imprinted genes, including loss of imprinting (LOI), plays a role in oncogenesis. In the present study, we investigated allelic expression of six imprinted genes in human lung adenocarcinomas as well as in matched normal lung tissue. Informative cases showing heterozygosity for the gene of interest were selected from 35 patients. LOI of the insulin‐like growth factor 2 gene (IGF2) and mesoderm‐specific transcript (MEST, also known as paternally expressed gene 1) was noted in 47% (seven of 15) and 85% (11 of 13) of informative cases, respectively. Monoallelic expression was maintained in all the matched normal tissues examined. LOI of IGF2 was seen more frequently in moderately to poorly differentiated adenocarcinomas. In contrast, H19, small nuclear ribonucleoprotein–associated polypeptide N gene (SNRPN), necdin gene (NDN), and long QT intronic transcript 1 (LIT1) exhibited consistent monoallelic expression in all the informative samples. These findings indicated that independent deregulation took place in imprinted genes and suggested that aberrant imprinting of IGF2 and MEST was involved in the development of lung adenocarcinoma.

Telomerase Activity Significantly Correlates with Chromosome Alterations, Cell Differentiation, and Proliferation in Lung Adenocarcinomas

Telomerase activity was examined by the telomeric repeat amplification protocol assay in 25 cases of lung adenocarcinoma, in relation to cancer cell differentiation, proliferation, and chromosome alterations. Telomerase activity, chromosome alterations, and cell proliferation assessed by Ki-67 labeling were significantly lower (P < .001 to .05) in well-differentiated (10 cases) than in moderately differentiated (8 cases) or poorly differentiated (7 cases) lesions. Telomerase activity by semiquantitative analysis with scoring of 0 to 3 was significantly correlated with similarly graded chromosome alterations (P < .05) and Ki-67 labeling indices (P < .002). Telomerase activity and chromosome alteration (T-C) indices generated by multiplication of telomerase activity and chromosome alteration scores also showed a significant correlation with cell differentiation. The Clara cell subtype, confirmed by electron microscopic analysis, significantly predominated in the well-differentiated group, showing a low grade of telomerase activity and chromosome alterations and low Ki-67 labeling indices, suggesting clinical relevance. No significant association of telomerase activity was found with p53 protein accumulation or Bcl-2 protein expression. The good correlation of telomerase activity with chromosome alterations, cell differentiation, and Ki-67 labeling indices suggests that this parameter might have potential application in estimation of prognosis.

Type AB thymoma accompanied by pure red cell aplasia and Good syndrome with CMV infection of tumor cells

Reported herein is a case of type AB thymoma accompanied by pure red cell aplasia (PRCA) and Good syndrome. The patient was a 55‐year‐old woman who was found to be anemic and to have an abnormal shadow at the left pulmonary hilus on routine medical examination. Bone marrow aspiration was performed and she was diagnosed as having PRCA. She also had hypogammaglobulinemia. The anemia was temporarily cured with oral prednisolone and cyclosporin A, and the patient underwent total thymectomy. The tumor was type AB thymoma, composed mainly of type A components; widespread spindle cell components showed slight to moderate infiltration of immature T‐cells. In addition, CMV inclusion bodies were scattered throughout this tumor. The CMV‐infected cells were tumor cells, because they were positive for pancytokeratin and negative for CD34. Several cases of Good syndrome with widespread CMV infection have been reported, but it is extremely rare for CMV‐inclusion bodies to be found in tumor cells. No thymoma cases involving CMV infection of tumor cells have been reported.

An immunohistochemical study of the mesenchymal and epithelial components of pulmonary chondromatous hamartomas

Twenty‐five cases of solitary pulmonary chondromatous hamartomas (PCH) were examined by immunohistochemistry to evaluate the mesenchymal and epithelial components. PCH composed of predominantly mature cartilage were designated as C type, those predominantly composed of fibromyxoid tissue as FM type, and those predominantly composed of adipose tissue as A type. FM type PCH revealed various amounts of cartilage in various developmental stages, adipose tissue and fibromyxoid tissue, compared with a uniform pattern of cartilage tissue in C type. The cells of transitional form between spindle cells, stellate cells and chondrocytes were present in FM type. Epithelial components in PCH were bronchial, bronchiolar and cuboidal cells, mostly at the periphery of PCH. S‐100 protein consistently stained chondrocytes, stellate and spindle cells in the fibromyxoid tissue of solitary PCH. Fibroblast growth factor was immunolocalized to chondrocytes, spindle and stellate cells in the fibromyxoid tissue. The collagen type was associated with differentiation from primitive mesenchymal cells to chondrocytes (i.e. type I and III collagen appeared in fibromyxoid matrix and type II collagen in the cartilaginous matrix). Fibronectin coordinately appeared with type I and III collagens. The proliferating cell nuclear antigen labeling index of epithelial cells was comparable to those of neoplastic mesenchymal cells, but it was not significantly different between C type and FM type PCH. The primitive mesenchymal cells in the bronchial walls of the control premature neonates were also observed. This immunohistochemical study showed that the progenitor mesenchymal cells in the bronchial and bronchiolar walls may differentiate along chondrocytes, lipocytes, and smooth muscle cells in PCH and that epithelial proliferation is reactive and closely associated with neoplastic proliferation of the mesenchymal component.

Local Control and Cosmetic Outcome after Sector Resection with or without Radiation Therapy for Early Breast Cancer

Breast conserving surgery and radiation therapy (RT) can achieve a more favorable cosmetic outcome than mastectomy in patients with early breast cancer. However, it is widely recognized that RT is an impediment to improving the cosmetic outcome. Between 1985 and 1993, 113 patients were enrolled in a prospective randomized study to examine whether or not RT could be avoided following sector resection in patients with Stage I and II (UICC) invasive breast cancer. There was no significant difference in the 8 year local recurrence free survival rate between the RT and non-RT groups (92.3% versus 89.8% respectively). The characteristics of suitable patients would be negative nodes and microscopically negative resection margins. In conclusion, sector resection without RT is a reasonable option for some patients with early breast cancer.

Multiple pulmonary hamartomas: Report of a case

Among lung tumors, multiple hamartomas are uncommon while multiple chondromatous hamartomas are extremely rare, with only 12 cases having been previously reported. A case of multiple pulmonary chondromatous hamartomas in a 58-year-old Japanese man who has been followed up for 28 years is herein presented.

Spontaneous esophageal rupture after gastrointestinal examination using barium

We experienced a case of spontaneous rupture of the esophagus after gastrointestinal examination using barium. A 48-year-old male experienced severe chest pain after vomiting following gastrointestinal examination. Chest X-ray revealed a right pneumothorax and pleural effusion by barium. We diagnosed spontaneous rupture of the esophagus and performed right thoracotomy 6 hours after onset of symptoms. At 10 cm above the diaphragm, there was a vertical perforation 3 cm in length. Following saline lavage, the ruptured esophageal wall was directly closed by the layer to layer method. The post operative course was uneventful and the patient was discharged 3 weeks after surgery. Cases of spontaneous rupture of the esophagus into the right thoracic cavity induced by gastrointestinal examination are extremely rare.