Kunio Araki

Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastases

In lung cancers, lymph node metastasis of cancer cells is one of the most important prognostic factors, and lymphatic vessel invasion (LVI) is very important in the stage preceding lymph node metastases. Recently, it has been reported that lymphatic vessel density (LVD) is associated with lymph node metastasis. The aim of the present study was to evaluate the relationship between LVD and LVI based on the immunohistochemical expression of podoplanin or D2‐40, which are new specific markers for lymphatic endothelium. Using 76 cases of pulmonary adenocarcinoma, the relationship between LVD and LVI, lymph node metastases, vascular endothelial growth factor C (VEGF‐C), VEGF‐D or hepatocyte growth factor (HGF) expression was investigated. LVD was significantly associated with LVI, lymph node metastases and VEGF‐D expression. LVI was also associated with lymph node metastases, histological subtype, VEGF‐C or VEGF‐D expression. High LVD, induced by VEGF‐C or VEGF‐D expression of cancer cells, is a good indicator of lymphatic metastases and LVI in pulmonary adenocarcinoma.

Expression of minichromosome maintenance 7 (MCM7) in small lung adenocarcinomas (pT1): Prognostic implication.

Minichromosome maintenance (MCM) proteins, essential molecules in the initiation and elongation of DNA replication, have been considered to be good indicators of cell proliferation. We examined the expressions of MCM7 and Ki-67 in lung adenocarcinomas (ACs) with a diameter less than 3cm (pT1), to clarify their pathobiological significance. Immunohistochemistry was conducted to obtain labeling indices (LIs%) for MCM7, MCM2 and Ki-67 in 100 surgically removed pT1 ACs. The LIs were compared with clinicopathological profiles and overall survival rates. The mean LIs of MCM7 and Ki-67 were 20.2+/-15.2% and 13.7+/-11.2%, the value being higher in the former than in the latter (P<0.01). MCM7 LIs were significantly correlated with sex, histological grade, histological subtype, tumor size, LIs of Ki-67, MCM2 and P53 (P<0.05). LIs of MCM7 and Ki-67 were significantly higher in the 84 non-bronchioloalveolar carcinomas than in the 16 bronchioloalveolar carcinomas (P<0.01). Kaplan-Meier survival curves showed that patients with higher MCM7 LIs had poorer prognosis in the 100 pT1 ACs as well as in the 73 stage I ACs. Multivariate Cox regression analysis confirmed that the LIs of MCM7, but not the LIs of MCM2 and Ki-67, was an independent prognostic marker in the 73 stage I ACs. These results suggest that MCM7 is an independent prognostic marker, being more reliable than MCM2 or Ki-67 in human pT1 ACs as well as in human stage I ACs.

MCM2 and Ki-67 Expression in Human Lung Adenocarcinoma: Prognostic Implications

Objective: The expressions of minichromosome maintenance protein 2 (MCM2), Ki-67, and p53 were examined to analyze their pathobiological significance in human lung adenocarcinomas. Methods: We performed Western blot analysis in six human lung adenocarcinoma cell lines and immunohistochemistry in 145 surgically removed adenocarcinomas to examine the MCM2 expression. Labeling indices (LIs; %) of MCM2, Ki-67, and p53 in the tumor cells were compared with clinicopathological profiles and overall survival rates. Results: MCM2 protein was detected in all cell lines examined, with specific bands. MCM2 LIs were significantly correlated with sex, histological type, differentiation, pathological stage, and LIs of Ki-67 and p53 (p < 0.05). Significantly higher LIs of MCM2 and Ki-67 were noted in the 122 non-pure bronchioloalveolar carcinomas than in the 23 pure bronchioloalveolar carcinomas (p < 0.01), and the prognosis was poorer in the former than in the latter (p < 0.01). Sex, pathological stage, and high LIs of MCM2 and/or Ki-67 were independent prognostic factors (p < 0.05). Conclusion: High LIs of MCM2 and/or Ki-67 suggest a poor prognosis in patients with lung adenocarcinoma (non-pure bronchioloalveolar carcinoma).

Expression of RUNX3 protein in human lung adenocarcinoma: implications for tumor progression and prognosis.

Runt‐related transcription factor 3 belongs to the runt domain family of transcription factors that play a pivotal role during normal tissue development and tumorigenesis in several organs. We directed our attention to the expression of RUNX3 protein in human lung AC and non‐neoplastic lung tissues, comparing the results with clinicopathological profiles. We evaluated the expression of RUNX3 protein in 17 pairs of lung AC and non‐neoplastic lung tissue. Furthermore, 98 lung AC were studied to examine the frequency of RUNX3‐positive cells. Western blot analysis showed a single band at 45 kDa in all 17 AC and non‐neoplastic tissues. Immunohistochemistry revealed immunoreactivity in alveolar type II pneumocytes or Clara cells. RUNX3 was expressed more frequently in the carcinomas with a BAC component than in those without (P < 0.01). Lower RUNX3 levels were associated with poorly differentiated types (P = 0.049). The five‐year survival rate was significantly higher in the 50 patients with higher levels of RUNX3 expression than in the 48 patients with lower levels (P = 0.027). The expression of RUNX3 protein in lung AC might play a pivotal role in tumor progression and patients’ survival. (Cancer Sci 2005; 96: 227–231)

A case of pulmonary typical carcinoid with an extensive oncocytic component showing intense uptake of FDG

Pulmonary carcinoid tumours, especially typical carcinoid, usually have lower FDG uptake than lung carcinoma.1 We present an unusual case of pulmonary carcinoid showing intense uptake of 18F-fluoro-deoxy-glucose (FDG). FDG-PET CT scan showed increased tracer concentration corresponding to the 3 cm round tumour in the left lingula (figure 1). The maximal standardised uptake value (SUV) of the tumour was 39. Bronchoscopy was performed to show an endobronchial red-coloured polypoid mass with a smooth surface in the left B5a. Cytology obtained by endobronchial brushing showed uniform round to oval …

Prognostic implication of lymphatic vessel invasion in stage IB (pT2aN0M0) non-small cell lung cancer

PurposeTo clarify the prognostic factors for recently revised stage IB non-small cell lung cancer.MethodsTwenty-six specimens of completely resected stage IB (pT2aN0M0) non-small cell lung cancer were studied. Clinicopathological profiles of the 26 patients, including age, sex, smoking status, tumor size, histology, pleural invasion, and lymphatic and blood vessel invasion, were assessed. Correlation between tumor recurrence and these factors was assessed by statistical analysis.ResultsLymphatic vessel invasion was the only statistically significant factor for postoperative tumor recurrence as assessed by multivariate analysis. Kaplan-Meier survival curves showed a 5-year recurrence-free rate of 77.8% in 26 patients with no lymphatic vessel invasion compared with 28.6% in those with lymphatic vessel invasion.ConclusionLymphatic vessel invasion of cancer cells was indicated as an independent prognostic factor in revised stage IB non-small cell lung cancer.

Cytoplasmic maspin expression is a predictor of poor prognosis in patients with lung adenocarcinoma measuring <3 cm

Maspin is known to be a tumour suppressor protein, and few studies focused upon its prognostic significance in patients with small‐size lung adenocarcinoma have been reported; however, its clinical significance remains controversial. We explored the prognostic value of maspin with particular reference to its subcellular localization in patients with resected lung adenocarcinoma measuring <3 cm.

Sarcoid-like reaction in Cryptococcus neoformans infection

We report a patient with Cryptococcus (C.) neoformans infection, who developed a case of sarcoid-like reaction (SLR). There have been reports of SLRs associated with malignancies. Although differentiating sarcoidosis from SLR is difficult, the patient was diagnosed as SLR because propionibacterium acnes bacterial (PAB) antibody staining of biopsy specimens was negative and the chest radiological findings improved after antifungal treatment. To our knowledge, this is the first report of SLR occurring during cryptococcal infection, and we believe that cryptococcal infection should be considered as a potential cause of SLR.

Desmoid tumor requiring differentiation from port-site relapse after surgery for lung cancer.

Thoracoscopic left lower lobectomy with lymph node dissection for lung cancer was performed in a 76‐year‐old man. The diagnosis was pT2aN2M0 adenocarcinoma. Sixteen months after surgery, CT revealed a pleural tumor measuring 38 mm at the surgical port wound. CT‐guided biopsy revealed fibroma. However, the tumor size increased 4 months after biopsy, and surgery was performed. An intraoperative diagnosis revealed benign fibroma. Thoracoscopic tumorectomy was conducted. The pathological diagnosis was desmoid tumor. As the margins of the resected specimen were positive, radiotherapy was performed. During the 16‐month follow‐up period, there has been no relapse. Pleural desmoid tumors must be differentiated from port‐site relapse.

Podoplanin expression in cancer-associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma.

Podoplanin expression in cancer‐associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early‐stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p‐stage) IA lung adenocarcinoma as categorised by the 8th edition of the tumour–node–metastasis classification for lung cancer.