Background: The aim of this retrospective study was to assess the prognostic value of serum tumor markers (carcinoembryonic antigen (CEA) and CYFRA21-1) in patients with pathologic (p-) stage I non-small cell lung cancer (NSCLC) undergoing complete resection. Methods: Two hundred and seventy-five patients (163 males, 112 females, mean age 67.1 years) with p-stage I NSCLC who underwent complete resection at our institution between April 1999 and October 2004 were examined. Patients who had received preoperative chemotherapy or radiotherapy were excluded, as were patients who had multiple malignancies including multiple lung cancer. The serum levels of tumor markers were measured using commercially available immunoassays within 1 month before surgical resection. Serum levels of CEA and CYFRA21-1 higher than 5.0 and 2.8 ng/ml, respectively, were considered as positive according to the manufacture's instructions. Results: The histological classification was adenocarcinoma in 193 patients, squamous cell carcinoma in 71, large cell carcinoma in 5, and other histological type in 6. One hundred and fiftyseven patients had T1 disease and 118 patients had T2 disease. The positive ratio of CEA and CYFRA21-1 was 25.7% and 13.7%, respectively, and in relation to histological type was 27.8% and 7.8% in adenocarcinoma, and 20.6% and 28.4% in squamous cell carcinoma. The overall 5-year survival rate was 79.3%. With a median follow-up of 35.5 month for surviving patients, those with initial CYFRA21-1 serum levels higher than 2.8 ng/ml had a significantly worse prognosis ( p = 0.0041). Patients with an elevated preoperative CEA level exceeding 5.0 ng/ml had a shorter disease-free survival period ( p = 0.0003). In patients with adenocarcinoma, a CEA level above 5.0 ng/ml was associated with shorter survival and early recurrence, whereas CYFRA21-1 showed no such association. In patients with squamous cell carcinoma, elevated preoperative CEA was not related to survival and recurrence. In these patients, preoperative CYFRA21-1 level exceeding 2.8 ng/ml was associated with a poorer outcome, whereas preoperative CYFRA21-1 level was not associated with cancer recurrence. Conclusion: The patients with p-stage I adenocarcinoma whose preoperative CEA level was high might be considered as good candidates for adjuvant chemotherapy. The prognostic value of CYFRA21-1 could not be confirmed for stage I NSCLC, and preoperative CYFRA21-1 level was not useful in selecting the candidates for adjuvant chemotherapy. #

Herpesvirus-associated ubiquitin-specific protease (HAUSP) directly stabilizes the tumour suppressor p53 by de-ubiquitination. Therefore, the HAUSP gene might play an important role in carcinogenesis. In this paper, HAUSP expression and p53 gene status have been studied in relation to the expression of p53 target genes in 131 patients with non-small cell lung cancer (NSCLC). p53 gene status was evaluated by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by sequencing. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was performed to evaluate the gene expression of HAUSP, p21, and bax. Immunohistochemistry was performed to evaluate the protein expression of p53, HAUSP, mdm2, p21, and bax. Fifty-nine carcinomas (45.0%) showed reduced expression of HAUSP, and 58 carcinomas (44.3%) had mutations of p53. Concerning tumour histology, HAUSP mRNA expression was significantly lower in adenocarcinomas than in squamous cell carcinomas (p = 0.0038), while the frequency of p53 mutation was significantly higher in squamous cell carcinomas than in adenocarcinomas (p = 0.0461). There was no significant difference in HAUSP mRNA expression according to p53 gene status. In total, 93 carcinomas (71.0%) showed either mutant p53 or reduced HAUSP expression. The down-regulation of HAUSP was associated with reduced p53 protein expression (p = 0.0593 in tumours with wild-type p53 and p = 0.0004 in tumours with mutant p53). Furthermore, p21 and bax protein expression was significantly lower in tumours with either mutant p53 or reduced HAUSP expression than in tumours with both wild-type p53 and positive HAUSP expression (p = 0.0440 and p = 0.0046, respectively). In addition, the simultaneous evaluation of both HAUSP expression and p53 gene status was a significant indicator of poor prognosis in adenocarcinoma patients (hazard ratio 4.840, p = 0.0357). These results suggest that reduction of HAUSP gene expression may play an important role in NSCLC carcinogenesis, especially in adenocarcinomas, through p53-dependent pathways.

We report five serial cases of ciliated muconodular papillary tumor (CMPT) of the lung. CMPT is characterized as a low-grade malignant tumor with ciliated columnar epithelial cells combined with goblet cells, typically presenting as peripheral lung tumor and often causing diagnostic or therapeutic problems. In the cases described here, all patients presented with abnormal chest shadow but no definitive symptoms. Although all tumors were peripheral, computed tomography (CT) revealed various radiographic findings including small lung nodules, ground-grass opacity or irregular-shaped consolidation. All patients underwent complete surgical resection, and no recurrence has been noted over follow-up. In all cases, pathological findings included columnar ciliated cells with mucus lakes, consistent with the immunohistochemical staining. As there are few reports on this tumor entity, which has not yet received a WHO classification, we believe our case series may be of interest.

We found that pT classification was a significant prognostic indicator for OS and DFS whereas tumor diameter, performance status, and sex were ones for OS. Single N2 metastasis and skip N2 metastasis were demonstrated as favorable prognostic factors for DFS, limited N2 metastasis was one for OS, and these should be considered as stratification factors for trial on adjuvant therapy.

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