Research on molecular mechanisms underlying the carcinogenesis of non-small cell lung cancer (NSCLC) may provide gene targets in critical pathways valuable for improving the efficacy of therapy and survival of patients with NSCLC. However, the molecular markers highly sensitive for the prognosis and treatment evaluation of NSCLC are not yet available. To explore candidates, we conducted an oligonucleotide microarray study with three pairs of NSCLC and normal lung tissue, and determined 8 differentially expressed genes including the Human MutT homologue (hMTH1), Surfactant protein D (SPD), Human hyaluronan binding protein 2 (HABP2), Crystalline-mu (CRYM), Ceruloplasmin (CP), Integrin alpha-11 subunit (ITGA11), Collagen type XI alpha I (COL11A1), and Lungspecific X protein (Lun X). Four lung cancer-related markers MUC-1, hTERT, hnRNP B1, and CK-19 were also incorporated for further analysis. The expression profiles of the twelve genes in seventy pairs of NSCLC tumor and normal lung tissue were then detected quantitatively by using membrane array and quantitative real-time PCR (qRT-PCR). The data of the membrane array and qRT-PCR were compared for consistency and the potential of these mRNA markers in clinical application. The results showed that membrane array and qRT-PCR obtained consistent data for the tested genes in both sensitivity and specificity (correlation coefficient 0.921, p<0.0001). For patients' clinicopathological characteristics, the overexpression of hMTH1, SPD, HABP 2, ITGA11, COL11A1, and CK-19 was significantly correlated with the pathological stage (p<0.05). In addition, the overexpression of hMTH1, SPD, ITGA11, and COL11A1 was correlated with lymph node metastasis and poor prognosis. This is the first report relating SPD to a prognosis marker for NSCLC. Moreover, the combined detection of these four mRNA markers by membrane array had a sensitivity of 89% and a specificity of 84% for NSCLC, significantly higher than these markers had achieved separately. In conclusion, we identified mRNA markers for NSCLC prognosis and therapy evaluation from differentially expressed genes determined by using microarray. Further studies are needed to collect the data of the mRNA markers used in clinical practice.

We report the case of a 68-year-old man with a newly defined rare entity of a peripheral pulmonary tumor, consisting of a nodular papillary lesion with papillary structures containing ciliated columnar and goblet cells, as well as floating tumor cells in the mucin pool. The conspicuous mucin pool was observed to be mimicking colloid adenocarcinoma in a low-power view, particularly in a frozen section slide. We originally reported it as an adenocarcinoma during intraoperative consultation. Immunohistochemically, the tumor cells exhibited a similar immunophenotype to pulmonary adenocarcinoma, except for the presence of focal ciliated and basaloid cells, which we found using CK5/6 and P63 immunostaining. No KRAS or EGFR mutation was found. We revised the diagnosis to that of a ciliated muconodular papillary tumor (CMPT). Four years after a wedge resection, the patient remained free of tumors. Although the malignant potential of CMPT cannot be ignored, a wedge resection with a safe margin might be a treatment option for CMPT patients.

In the present study, we addressed the molecular mechanism of the downregulation of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK), a critical tumor suppressor that can potently inhibit angiogenesis and metastasis, in non-small cell lung cancer and its clinical significance. The methylation status of the RECK gene promoter was studied by methylation-specific polymerase chain reaction. RECK mRNA and protein levels were investigated by reverse transcription-polymerase chain reaction and western blot analysis. Downregulation of RECK was observed in 60% of the 55 tumors analyzed. Using methylation-specific polymerase chain reaction analysis methylation of the RECK promoter was detected in 63.6% (35/55) of the tumor tissues. A strong correlation between downregulation and promoter methylation was found in these tumors (P = 0.000005). More importantly, downregulation of RECK significantly correlated with lymph node metastasis (P = 0.038). T he reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene was isolated as a transformation suppressor gene that induced flat reversion in v-K-ras-transformed NIH/3T3 cells.(1) This gene encodes a membrane-anchored glycoprotein that can negatively regulate matrix metalloproteinase-2 (MMP-2) and MMP-9 activities and inhibit tumor angiogenesis and metastasis.(2,3) Whereas RECK mRNA is highly expressed in most normal human tissues and untransformed cells, it is downregulated or undetectable in many tumor cell lines or in cells ectopically expressing active oncogenes.(2) Pathological studies have demonstrated that RECK downregulation is found in human cancers including pancreatic cancer, breast cancer, non-small cell lung cancer and colon cancer.(4 -7) In addition, reduced RECK expression correlates with poor prognosis in these cancers. However, the molecular mechanism that causes gene silencing of RECK in cancer cells is still unknown.Mutations in the K-ras proto-oncogene are found frequently in non-small cell lung cancer.(8) Aberrant activation of this oncogene has been implicated in many aspects of malignant phenotypes including proliferation, transformation, invasion and metastasis. Numerous studies have shown that oncogenic ras increases the metastatic ability of transformed cells.(9-11) However, the underlying mechanism is poorly characterized. Recently, we addressed the effect of oncogenic ras on RECK expression using an in vitro inducible system.(12) Our results showed that ras activation stimulates the expression of DNA methyltransferase 3b (DNMT3b), promotes DNMT3b binding to the RECK promoter and represses RECK expression via methylation of the promoter. We also found that human lung cancer cells harboring K-ras mutations exhibit increased promoter methylation and reduced expression of the RECK gene.(12) To verify the results observed in our previous study, we examined the methylation status of the RECK promoter in 55 lung tumor tissues. Moreover, we studied whether RECK promoter methylation correlated with K-ras mutation and other clinicopa...

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Intrathoracic extramedullary haematopoiesis (EMH) is a rare entity that is usually asymptomatic. A 44 year old man with alpha-thalassaemia is described who developed dyspnoea and massive left sided haemothorax. The haemoglobin disorder was established by Hgb H staining and haemoglobin electrophoretic studies. The DNA analysis revealed it to be a case of double heterozygous terminal codon mutation with the genotype CS / T . Computed tomographic scanning and magnetic resonance imaging of the thorax showed multiple paravertebral masses which were found by thoracoscopic biopsy to be extramedullary haematopoiesis. Although no additional sclerosing pleurodesis or low dose radiation therapy was given, the lung expanded well and there has been no recurrence of haemothorax to date.