Expression of Bone Morphogenetic Protein-7 Significantly Correlates With Non-small Cell Lung Cancer Progression and Prognosis: A Retrospective Cohort Study.

BACKGROUND: Bone morphogenetic protein-7 (BMP-7) is a signaling molecule belonging to the transforming growth factor-ß superfamily. Recent studies have demonstrated that BMP-7 is expressed in various human cancers and plays an important role in the progression of their cancers. The purpose of this study was to investigate the clinicopathologic and prognostic impact of BMP-7 expression in clinical samples of non-small cell lung cancer. METHODS: This study enrolled 160 patients with non-small cell lung cancer who underwent complete resection. Expression of BMP-7 in cancer tissue was evaluated by immunohistochemistry. Correlations between expression of BMP-7 and clinicopathologic factors and prognosis were analyzed. RESULTS: In non-small cell lung cancer, BMP-7 expression was identified not only in cell membranes but also in the cytoplasm of cancer cells. Expression of BMP-7 correlated with p-T (P = .047), N factor (P = .013), and p-stage (P = .046). Overall survival rate was significantly lower in the BMP-7-positive group than in the BMP-7-negative group (P = .004). Multivariate analysis indicated that BMP-7 expression was one of the independent prognosis factors of overall survival (P = .021). Furthermore, among patients with postoperative recurrence (n = 58), the BMP-7-positive group (n = 29) had a significantly poorer prognosis than the BMP-7-negative group (n = 29) (P = .012). CONCLUSIONS: Expression of BMP-7 in non-small cell lung cancer was correlated with clinicopathologic factors and poorer prognosis. BMP-7 expression may be a useful predictor of aggressive activity of tumor behavior and postoperative outcome of patients with non-small cell lung cancer.

Production of a High-affinity Monoclonal Antibody Reactive with Folate Receptors Alpha and Beta.

Folate receptors α (FRα) and ß (FRß) are two isoforms of the cell surface glycoprotein that binds folate. The expression of FRα is rare in normal cells and elevated in cancer cells. Thus, FRα-based tumor-targeted therapy has been a focus area of laboratory research and clinical trials. Recently, it was shown that a significant fraction of tumor-associated macrophages expresses FRß and that these cells can enhance tumor growth. Although FRα and FRß share 70% identity in their deduced amino acid sequence, a monoclonal antibody (MAb) reactive with both receptors has not been developed. A MAb that can target both FRα-expressing cancer cells and FRß-expressing tumor-associated macrophages may provide a more potent therapeutic tool for cancer than individual anti-FRα or anti-FRß MAbs. In this study, we developed a MAb that recognizes both FRα and FRß (anti-FRαß). The anti-FRαß specifically stained trophoblasts and macrophages from human placenta, synovial macrophages from rheumatoid arthritis patient, liver macrophages from cynomolgus monkey and common marmoset, and cancer cells and tumor-associated macrophages from ovary and lung carcinomas. Surface plasmon resonance showed that the anti-FRαß bound to soluble forms of the FRα and FRß proteins with high affinity (KD=6.26×10(-9) M and 4.33×10(-9) M, respectively). In vitro functional analysis of the anti-FRαß showed that this MAb mediates complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis of FRα-expressing and FRß-expressing cell lines. The anti-FRαß MAb is a promising therapeutic candidate for cancers in which macrophages promote tumor progression.

Intra-bronchial migration of peritoneal catheter of lumboperitoneal shunt.

BACKGROUND: A rare case of intra-bronchial migration of peritoneal catheter of lumboperitoneal (LP) shunt was treated under the bronchoscopic and fluoroscopic observation. CASE DESCRIPTION: A 71-year-old man, who underwent LP shunt installation due to idiopathic normal pressure hydrocephalus a year before, presented with history of high fever and sputum production. Roentgenography and computed tomography of the chest revealed migration of distal end of the peritoneal catheter into the left main bronchus. Migrated catheter was gently extracted through the abdominal wound incision under the bronchoscopic and fluoroscopic observation. Contrast material infused into the catheter did not spread into the pleural cavity. The patient was free of the symptoms within 2 postoperative weeks. Moreover, he underwent the ventriculo-peritoneal shunt surgery 1-month later. CONCLUSION: This is the first case of the migration of peritoneal catheter of LP shunt into the main bronchus.

A case of resected plasma cell type castleman's disease with intramediastinal lymph nodes spread.

We report a case of resected plasma cell (PC) type Castleman's disease (CD) in a 21-year-old female who had an anterior mediastinal mass with additional surrounding nodules. She was aware of low-grade fever and fatigue for several years. From hematological and biochemical examinations, elevated inflammatory responses and levels of serum IgG (2908 mg/dL) and IL-6 (22.2 pg/mL) were observed. She was diagnosed with PC type CD by needle biopsy under computed tomography (CT) guidance. It was thought that the lesion was localized in the mediastinum. Then, mediastinal adipose tissue including the tumor, additional nodules and thymus were removed. The histological findings of PC type CD were found not only in the main tumor but also in surrounding swollen lymph nodes. Her symptoms improved and inflammatory responses decreased after the operation. No recurrence has been observed for 5 years after the operation.

The elevation of serum napsin A in idiopathic pulmonary fibrosis, compared with KL-6, surfactant protein-A and surfactant protein-D.

BACKGROUND: Napsin A, an aspartic protease, is mainly expressed in alveolar type-II cells and renal proximal tubules and is a putative immunohistochemical marker for pulmonary adenocarcinomas. This study sought to determine whether napsin A could be measured in the serum to evaluate its relationship to idiopathic pulmonary fibrosis (IPF) and determine whether renal dysfunction might affect serum napsin A levels. METHODS: Serum levels of napsin A were measured in 20 patients with IPF, 34 patients with lung primary adenocarcinoma, 12 patients with kidney diseases, and 20 healthy volunteers. Surfactant protein (SP)-A, SP-D, and Krebs von den Lungen-6 (KL-6) levels in serum and pulmonary function tests were also evaluated in IPF patients. RESULTS: Circulating levels of napsin A were increased in patients with IPF, as compared with healthy controls, and they correlated with the severity of disease. Moreover, the serum napsin A levels were not elevated in patients with pulmonary adenocarcinoma or renal dysfunction. The distinguishing point between IPF and the controls was that the area under the receiver operating characteristic curve (ROC) of napsin A was larger than that of KL-6, SP-A, or SP-D. CONCLUSION: These findings suggest that serum napsin A may be a candidate biomarker for IPF.

EGFR mutations and human papillomavirus in lung cancer.

Our previous study reported a frequent detection of human papillomavirus (HPV) genome in primary lung adenocarcinomas of the recurrent patients who were responsive to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, suggesting that HPV presence in lung cancer may be related to a genetic background related to EGFR mutations. The present study examined the association between the HPV presence and mutations in exons 19 and 21 of EGFR gene in Japanese lung cancer patients. Thirteen (31%) out of 42 cases had EGFR mutations. Although these mutations were tended to be observed in females, non-smokers, or adenocarcinomas, there was no statistically significant associations. HPV DNA was found in 7/42 (17%) lung tumors. The frequency of HPV presence did not differ in histological types. The presence of HPV DNA was significantly related to EGFR mutations (P=0.021), especially in adenocarcinomas of the lung (P=0.014). HPV-positive lung tumors accounted for 38% and 7% of those with and without EGFR mutations, respectively. Our results suggest that EGFR mutations are associated with HPV presence in Japanese patients with lung cancer.

FDG-PET/CT finding of benign metastasizing leiomyoma of the lung.

We report a case of multiple benign metastasizing leiomyoma (BML) lung nodules showing faint or non-avid uptake of F-18 fluorodeoxyglucose (FDG) (respective 1-hour early and 2-hour delayed maximum standardized uptake values; 1.3 or less and 1.2 or less) in a 50-year-old woman with a history of hysterectomy for uterine leiomyoma at the age of 38 years. When multiple lung nodules show faint or non-avid FDG uptake in a patient with a history of hysterectomy for uterine leiomyoma, BML should be included in the differential diagnosis.

Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas.

A number of studies have reported the presence of human papillomavirus (HPV) in lung carcinoma. Interestingly, its detection rate appears to differ histologically and geographically. The present study examined 30 adenocarcinomas and 27 squamous cell carcinomas of the lung in a southern area of Japan, and detected high-risk HPV genome in 9 (30%) adenocarcinomas and 2 (7%) squamous cell carcinomas, using PCR with SPF10 primers and INNO-LiPA HPV genotyping assay. The difference of HPV detection rates in adenocarcinomas and squamous cell carcinomas was statistically significant (P=0.044, Fisher's exact test). HPV-16 was the most prevalent HPV genotype, and was detected in 27% (8/30) of adenocarcinomas and in 7% (2/27) of squamous cell carcinomas. High-risk-HPV positive carcinomas had decreased proportions of pRb (P=0.107) and significantly increased proportions of p16INK4a expressing cells (P=0.031) when compared to HPV-negative lung carcinomas. All HPV-16-positive cases were considered to have an integrated form of HPV-16 but its viral load was low (geometric mean = 0.02 copy per cell). In 20 additional adenocarcinomas treated with gefitinib, a tyrosine kinase inhibitor specific for epidermal growth factor receptor, the presence of HPV was examined. Note that East Asian ethnicity is a predictive factor of gefitinib response. High-risk HPV genome was found in 75% (6/8) of adenocarcinomas with complete or partial response to gefitinib but was not found in the remaining 12, which did not respond to gefitinib. In conclusion, the present study suggests that high-risk HPV may be more strongly related to adenocarcinomas, particularly gefitinib-responsive adenocarcinomas, when compared to squamous cell carcinomas. However, its low viral load makes it difficult to determine the etiological significance of these findings.

Clinical outcome of metastatic uterine leiomyosarcoma and carcinosarcoma in a single institute.

AIM: To investigate the clinical outcome of uterine sarcomas, particularly in patients with pulmonary and abdominal metastasis, treated at a single institute. METHODS: We identified five patients with uterine leiomyosarcoma (LMS), one patient with endometrial stromal sarcoma (ESS), and three patients with carcinosarcoma (CS) between 2003 and 2006. RESULTS: All patients underwent at least hysterectomy and bilateral adnectomy. All five LMS cases (two patients in International Federation of Obstetrics and Gynecology stage I and three in stage III) recurred: one patient showed metastasis to the lung and four patients showed metastasis to the abdomen 16.6 months (mean) after hysterectomy. Two of three (66.7%) CS recurred: one patient showed metastasis to the lung and the other to the abdomen 5 months (mean) after hysterectomy. The ESS (stage I) patient showed metastasis to the lung 11 months after hysterectomy. Five patients with metastases received surgical interventions (two pulmonary resections and three abdominal resections), and all of these patients are currently alive 1.1-5.1 years postoperatively. Two patients with CS (stage I) and one patient with LMS (stage III) died of sarcoma dissemination, but neither of these three patients had undergone surgical intervention after hysterectomy (one for pulmonary and two for abdominal metastases). CONCLUSIONS: Resection of lung and abdominal metastases in uterine LMS and CS is beneficial to improve patient survival.

Primary synovial sarcoma of the sternum: computed tomography and magnetic resonance imaging findings.

We report the computed tomography (CT) and magnetic resonance imaging (MRI) findings of a rare case of synovial sarcoma of the sternum in an 86-year-old man. CT demonstrated an inhomogenously enhanced soft-tissue-density mass of the sternum that destroyed bone cortex and protruded anteriorly. On MRI, the tumor showed a multinodular mass with internal septation and heterogeneous enhancement. These CT and MRI findings were nonspecific, but were similar to those of soft tissue synovial sarcomas. The tumor was more clearly demarcated by MRI than CT. This is the first report concerning the CT and MRI findings of synovial sarcoma of the sternum. Synovial sarcoma should be added to the gamut of primary malignant neoplasms of the sternum.

[A long-term surviving patient with invasive thymoma who underwent radiotherapy and/or resection for chest wall, intrathoracic and intrapelvic recurrent tumors].

A 49-year-old woman with myasthenia gravis who underwent left panpleuropneumonectomy for an invasive thymoma that disseminated through the left thoracic cavity. After six year, radiotherapy was conducted on the recurrent tumor in the left anterior chest wall. Two years later, the recurrent tumors in the intrapelvic and intrathoracic cavities were resected. It was thought that long-term survival was obtained by combining radiotherapy and surgical treatment in view of the patient's general condition, and of the recurrent invasive thymoma present in this case.