Phil Jo Choi

Relationship between micropapillary component and micrometastasis in the regional lymph nodes of patients with stage I lung adenocarcinoma.

Aims:  To determine whether a micropapillary component is a prognostic predictor, with particular reference to nodal micrometastasis, in patients with stage I lung adenocarcinomas.

Forkhead box M1 expression in pulmonary squamous cell carcinoma: correlation with clinicopathologic features and its prognostic significance ☆

Forkhead box M1 (FoxM1) transcription factor has been shown to play important roles in regulating the expression of genes that are involved in cell proliferation, differentiation, and transformation by promoting both G(1)/S and G(2)/M transition. Although it has been reported that the FoxM1 signaling network is frequently deregulated with an up-regulated FoxM1 expression in human malignancies, the role of FoxM1 in lung cancer remains to be determined. We performed immunohistochemical detection of FoxM1 protein in 69 tissue samples from patients with primary pulmonary squamous cell carcinoma using a tissue microarray, and Western blotting was done to confirm the immunohistochemical observations. FoxM1 immunoreactivity was observed in 26 (37.7%) of the 69 squamous cell carcinoma cases. Analysis of the FoxM1 expression in 12 squamous cell carcinoma tissues and 2 normal lung tissues by Western blotting confirmed the immunohistochemical results. A FoxM1 expression was more frequently detected in the moderately or poorly differentiated squamous cell carcinomas than in the well-differentiated squamous cell carcinomas (P = .008). The tumors with a positive FoxM1 expression more frequently showed lymph node metastasis (P = .027) and an advanced American Joint Committee on Cancer stage (P = .049). The Kaplan-Meier survival curves demonstrated that patients with a positive FoxM1 expression had a significantly shorter survival time than those patients with a negative FoxM1 expression (P = .003). The multivariate analysis revealed that the FoxM1 expression was an independent poor prognostic factor (P = .018). A subset of pulmonary squamous cell carcinoma with a FoxM1 expression was associated with progressive pathologic features and an aggressive clinical course.

Expression of double-stranded RNA-activated protein kinase in small-size peripheral adenocarcinoma of the lung.

The authors investigated the protein expression of double‐stranded RNA‐activated protein kinase (PKR), which was identified by using a previous cDNA microarray study, to discover PKRs correlations with several pathological parameters and to elucidate its role in neoplastic transformation and progression of lung adenocarcinomas. Immunohistochemistry for PKR was performed and a semiquantitative scoring method was calculated based on staining intensity and percentage of immunoreactive tumor cells (high vs low) for one bronchioloalveolar carcinoma (BAC), 16 adenocarcinomas consisting of BAC and invasive carcinoma (mixed) and 21 invasive adenocarcinomas without BAC (invasive). The BAC had high‐grade expression and the mixed type tended to more frequently show high‐grade expression than the invasive type (P = 0.028). There were no significant associations with age, tumor size, lymph node metastasis, lymphovascular invasion or the pathological stage. The Kaplan–Meier survival curves demonstrated that the patients with high‐grade PKR expression had significantly shorter survival periods than those patients with low‐grade PKR expression (P = 0.018). These results do not support the concept of PKR as a tumor suppressor in small‐size peripheral adenocarcinomas of the lung.

Pulmonary tuberculosis in five young infants with nursery exposure: clinical, radiographic and CT findings

Abstract Clinical, radiographic (n = 5) and CT findings (n = 4) of five Korean infants ranging in age from 2 to 3 months with confirmed tuberculosis were retrospectively analysed. All of the patients were symptomatic, anergic to tuberculin, and had a positive culture of Myobacterium tuberculosis in gastric aspirates. The probable source of infection was the hospital in which they were born. CT scans demonstrated hilar and mediastinal lymph node enlargement with central low attenuation and peripheral enhancement in all cases. CT may be useful in diagnosis by demonstrating characteristic adenopathy and disseminated disease in young infants.

Comparison of cadherin-17 expression between primary colorectal adenocarcinomas and their corresponding metastases: the possibility of a diagnostic marker for detecting the primary site of metastatic tumour

that the syncytial cells were positive, consistent with previous publications, but that the cytotrophoblast was negative. The photomicrograph I, depicting ‘trophoblastic areas associated with embryonal carcinoma’, actually shows weak staining in the mononuclear cells, consistent with the weak expression of cytotrophoblast described in several publications, and correlates with immunohistochemical and cell culture data obtained using human placenta. Mature and immature teratoma has been described to show no to focal expression of GPC3. In particular, I quantified neuroepithelium (immature teratoma) previously in both gonadal and extragonadal germ cell tumours and found 40% to be positive. In addition to neuroepithelium, other teratomatous elements that I have noted to be positive include primitive-appearing spindle cells, fetal type glands ⁄ primitive tubules, cartilage anlage and mature-appearing columnar epithelial-lined glands. GPC3 expression was assessed semiquantitatively in these previous publications (0, <5%; 1+, 5–10%; 2+, 11–50%; 3+, >50%) and most cases of mature teratoma were classified as negative, as fewer than 5% of teratomatous cells were positive. Similar findings regarding mature and immature teratomatous elements have been described by other authors. Regarding yolk sac tumour, Preta et al. note that hepatoid areas of tumour were positive, as has been reported previously by Pantanowitz and Otis. Preta et al. note that GPC3 is more sensitive than alphafetoprotein (AFP) for testicular yolk sac tumour, similar to our findings. The authors state that the syncytial cells within seminoma were negative, which I have not tested, but which have been reported by two other groups to be positive. Preta reports that spermatocytic seminoma was positive, which I have not tested, but this disagrees with a previous report stating that this tumour was negative. In summary, GPC3 is expressed frequently in yolk sac tumour and choriocarcinoma, with no expression in seminoma, focal to no expression in mature teratoma and embryonal carcinoma and low expression in immature teratoma.

A different TRAP220 expression in distinct histologic subtypes of lung adenocarcinoma and the prognostic significance

Adenocarcinomas are a very heterogeneous subgroup of lung cancers, in which oncogenesis is linked to different molecular events. Recent evidence suggests that the hormonal status may contribute to the pathogenesis of lung adenocarcinoma. TRAP220 is the main subunit of the TRAP/Mediator complex and it binds to nuclear hormone receptors in the presence of their cognate ligand, as a cofactor of the transcription machinery. Since TRAP220 is an essential coactivator that interacts directly with estrogen receptor β (ERβ), we examined the expression of TRAP220 protein to investigate its role in lung adenocarcinoma, with particular attention being paid to its different histologic subtypes and the ERβ expression. We performed immunohistochemical detection of TRAP220 and ERβ protein in eighty-seven tissue samples from lung adenocarcinoma patients by using a tissue microarray, and Western blotting was then done to confirm the immunohistochemical observations. TRAP220 immunoreactivity was observed in 27 (31.0%) of the 87 adenocarcinoma cases. Analysis of the TRAP220 expression by Western blotting confirmed the immunohistochemical results. The TRAP220 expression was more frequently positive in the non-solid subtypes (bronchioloalveolar, acinar, and papillary patterns) than that in the solid subtype (P=0.027) and the TRAP220 expression was more frequently positive in the well-differentiated adenocarcinomas than that in the moderately or poorly differentiated adenocarcinomas (P=0.005). The tumors with a negative TRAP220 expression were larger in size (P=0.048) and they more frequently showed lymph node metastasis (P=0.002), pleural invasion (P=0.026) and an advanced TNM stage (P=0.012). The frequency of the TRAP220 expression in the cases with an ERβ expression was significantly higher than that in those cases without an ERβ expression (P=0.003). The Kaplan-Meier survival curves demonstrated that the patients with a positive TRAP220 expression had a significantly longer survival time than those patients with a negative TRAP220 expression (P=0.014). The multivariate analysis revealed that a TRAP220 expression was an independent good prognostic factor (P=0.049). Our data may be useful to understand the different biologic basis for the development and progression of the subtypes of lung adenocarcinoma.

Sodium/iodide symporter expression in primary lung cancer and comparison with glucose transporter 1 expression.

The aim of the present study was to evaluate the expression of sodium/iodide symporter (NIS) and glucose transporter 1 (Glut1) in 139 primary lung cancers on immunohistochemistry, and to determine the diagnostic utility of NIS as an imaging reporter. Immunoreactivity for NIS and Glut1 was noted in 75 (54.0%) and 72 (51.8%) of the 139 cases, respectively. Analysis of NIS expression on Western blot confirmed the immunohistochemistry. NIS expression was significantly higher in the adenocarcinomas than in the other carcinomas, and Glut1 expression was significantly higher in the squamous cell carcinomas than in the other carcinomas (each P < 0.0001). The frequency of NIS expression in those carcinomas lacking Glut1 expression was significantly higher than in those with Glut1 expression (P = 0.012). Among 64 adenocarcinomas, the frequency of the NIS(+)/Glut1(−) phenotype was 61.0%, which was the most frequent expression pattern. By studying the expression pattern of NIS in lung cancer, the present paper provides a helpful foundation for examining the potential utility of NIS‐mediated radioiodide as an alternative diagnostic modality, especially for the management of patients with lung adenocarcinoma lacking Glut1 expression.

Primary Extraskeletal Mesenchymal Chondrosarcoma of the Anterior Mediastinum

Primary extraskeletal mesenchymal chondrosarcoma (EMC) of the mediastinum is an extremely rare disease. To date, only seven cases have been reported in the literature 1-4 since it was first reported by Chetty in 1990.1 We experienced a case of primary mediastinal EMC presenting as an anterior mediastinal mass, a previously unreported site. Here, we describe the characteristic features of the lesion with a review of the literature to emphasize that EMC should be considered in the differential diagnosis of mediastinal tumors.

Characteristics of additional primary malignancies in Korean patients with non-small cell lung cancer.

BACKGROUND Long-term cancer survival results in increasing numbers of multiple primary malignancies in one person, which represents growing clinical challenge in patients with lung cancer. This study was intended to assess the incidence rate, temporal relationship, and characteristics of additional primary malignancies (APM) in Korean patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS We reviewed all 632 NSCLCs (313 adenocarcinomas, 276 squamous cell carcinomas, and 43 other NSCLCs) patients who underwent curative resection of NSCLC at the Dong-A University Medical Center from January 1991 to December 2009. We used the hospital information system and medical record to collect data about these patients and their tumors. In the data base, the following parameters were recorded: patients demographics (age, gender and smoking habit), time interval between the diagnosis of the NSCLC and APM, NSCLC characteristics (date of diagnosis, histology, TNM staging, operative details, and survival) and characteristics of APM (site of tumor, date of diagnosis, histology, TNM staging, operative details, and survival). RESULTS Eighty-one (12.8%) of the 632 patients with NSCLC had APMs. Thirty-three patients (40.8%) had APM in their history [occurring earlier than six months or more before NSCLC diagnosis; prior (P) group], 18 patients (22.2%) were diagnosed with an APM synchronously [diagnosed within six months before or after NSCLC; synchronous (S) group], and the remaining 30 patients (37.0%) were diagnosed with an APM during the follow-up period [occurring six months or more after NSCLC diagnosis; metachronous (M) group]. The second primary malignancy occurred most often two to five years in both P group (39.4%) and M group (36.7%). The most frequent APM was stomach cancer (25.0%), followed by colorectal cancer (19.0%), and thyroid cancer (10.7%). Interestingly, we found difference in the incidence of APM between different NSCLC histotypes. In the adenocarcinoma group, colorectal cancer was the most frequently discovered [12 of 46 events (26.1%)], followed by thyroid cancer [9 of 46 events (19.6%)]. In the squamous cell carcinoma group, stomach cancer occurred most frequently [12 of 36 events (33.3%)]. CONCLUSIONS APMs are commonly seen in patients with NSCLC, either preceding or following its occurrence. Therefore, it is important to recognize the characteristic of NSCLC patients with APM in order to detect the second primary malignancy as early as possible and to achieve a possible cure of disease.

Primary Pulmonary Myxoid Liposarcoma with Translocation t(12;16)(q13;p11) in a Young Female Patient: A Brief Case Report

Primary liposarcoma of the lung is an extremely rare disease. To date, only 14 cases have been reported in the literature. We experienced a case of myxoid liposarcoma of the lung treated by surgery. The tumor was well-defined, solid, lobulated mass measuring 3.5×2 cm, involving the bronchus of the left lower lobe. Microscopically, myxoid liposarcoma was identified. The fluorescence in situ hybridization confirmed the presence of a reciprocal translocation involving DNA damage-inducible transcript 3 (DDIT3) and fused in sarcoma (FUS) genes. The patient is still alive with no recurrence or metastasis at the time of writing this report (on 20 months postoperatively). To our knowledge, this is the first cytogenetic case report of pulmonary myxoid liposarcoma.