Masaki Tomita

Effect of mast cells on tumor angiogenesis in lung cancer

BACKGROUND We conducted a retrospective study to clarify the effect of mast cells on tumor angiogenesis in lung cancer patients. METHODS Formalin-fixed and paraffin-embedded tumor sections were used in this study. Parenchymal mast cells were stained with Alcian blue and safranin O. The number of mast cells per ten fields at a magnification of 200x was counted under light microscopy, and the average count was determined. To highlight the microvessels, endothelial cells were stained with anti-human factor VIII antibody. After the microvessel count was determined, the microvessels were further stained with Alcian blue and safranin O to show areas of mast cell infiltration. Expression of vascular endothelial growth factor was assessed using a polyclonal antibody. RESULTS We found a significant correlation between mast cell count and microvessel density. This correlation was also observed in patients with adenocarcinoma (p < 0.001) as well as in patients with squamous cell carcinoma (p < 0.01). Double staining of the microvessels showed highly angiogenic areas densely populated with mast cells. Although we detected a slight trend toward a correlation between vascular endothelial growth factor expression and microvessel density, it was not statistically significant. We found no association between vascular endothelial growth factor expression and mast cell count. CONCLUSIONS There appears to be a direct correlation between the number of mast cells and tumor angiogenesis in patients with lung cancer, and this relationship appears to be independent of vascular endothelial growth factor expression.

Prognostic impact of thrombocytosis in resectable non-small cell lung cancer

Relationship between thrombocytosis and poor prognosis has been reported in lung cancer. However, the majority of previous studies included many advanced stage and small cell lung cancer patients. Few studies focused on resectable non-small cell lung cancer patients. In the present study, therefore, consecutive 240 non-small cell lung cancer patients who received surgical resection were reviewed retrospectively, and investigated the survival impact of preoperative platelet count. In our results, the frequency of preoperative thrombocytosis was only 5.83% (14/240). The 5-year survival of patients with and without thrombocytosis was 28.87% and 63.73%, respectively. Both univariate and multivariate analyses indicated the independent prognostic impact of thrombocytosis. The present study is the first evaluation of prognostic effect of thrombocytosis in patients with resectable non-small cell lung cancer. Preoperative platelet count was a prognostic factor for resectable non-small cell lung cancer patients.

Correlation between mast cells and survival rates in patients with pulmonary adenocarcinoma

BACKGROUND A retrospective study on the correlation between mast cells and survival rates of 90 pulmonary adenocarcinoma patients is reported. METHODS Surgical specimens were stained with alcian blue and safranin O, and parenchymal mast cells were counted. Based on the counts, the patients were divided into two groups: Group A had mast cell counts of > 20/microscopic field; Group B, < 20. TNM staging and histological findings were recorded for both groups. Phenotypes of mast cells were determined using enzymehistochemistry. Total count numbers, the histological differentiation of adenocarcinomas, and phenotypes were evaluated with regard to patient survival rates. RESULTS Group A had a 5-year survival rate of 45.85%, as compared with Group Bs rate of 16.32% (P < 0.01). Group A also represented a higher percentage of well-differentiated adenocarcinomas. In both cancerous tissue and normal lung tissue, the predominant mast cell phenotype was MC(T). CONCLUSIONS There appears to be a direct relationship between the number of mast cells and clinical outcome in patients with pulmonary adenocarcinoma, even though the mast cells exhibited no significant phenotypic changes.

Clinical and immunohistochemical study of eight cases with thymic carcinoma.

BackgroundThymic carcinoma is a rare neoplasm with extremely poor prognosis. To evaluate the biological characteristics of thymic carcinoma, we reviewed 8 patients.MethodsThere were 2 men and 6 women: ages ranged from 19 to 67 years old (mean 54.8 years). None of these patients had concomitant myasthenia gravis and pure red cell aplasia. No patient had stage I disease, 1 stage II, 5 stage III, and 2 stage IV. The pathologic subtypes of thymic carcinoma included 5 squamous cell carcinomas, 1 adenosquamous cell carcinomas, 1 clear cell carcinoma, and 1 small cell carcinoma. Immunohistochemical study was performed using antibodies against p53, bcl-2, Ki-67, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), nm23-H1, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) and factor VIII.ResultsCurative resection could be done in 4 patients (50%). Our data indicates a trend toward an association between complete resection and patient survival. Expression of p53, bcl-2, CEA, EMA, nm23-H1, VEGF and FGF-2 was detected in 5/8, 3/8, 4/8, 5/8, 6/8, 5/8 and 3/8, respectively. Mean Ki-67 labeling index and microvessel density was 7.01 and 34.36 (per 200× field), respectively. When compared with our previous studies, immunohistochemical staining of these proteins in thymomas, the expression rates of these proteins in thymic carcinomas were higher than those in thymomas.ConclusionsIn this small series, it is suggested that a complete resection suggests a favorable result. Immunohistochemical results reveal that the expression of these proteins might indicate the aggressiveness of thymic carcinoma.

Maximum SUV on positron emission tomography and serum CEA level as prognostic factors after curative resection for non‐small cell lung cancer

Aims:  The relationship between the maximum standardized uptake values (SUVmax) on positron emission tomography (PET) and serum carcinoembryonic antigen (CEA) level in non‐small cell lung cancer (NSCLC) patients was investigated.

Serum carcinoembryonic antigen level in non-small-cell lung cancer patients with preoperative normal serum level

ObjectiveThe prognostic significance of serum carcinoembryonic antigen (CEA) levels in non-small-cell lung cancer (NSCLC) patients with a normal serum CEA level (<5.0 ng/ml) was examined.MethodsA total of 220 consecutive NSCLC patients with preoperative normal serum CEA levels were included. Patients were subdivided into two groups: preoperative serum CEA level ≥2.5 and <2.5 ng/ml.ResultsThe 5-year survival of patients with preoperative serum CEA level less and more than 2.5 ng/ml were 79.62% and 62.0%, respectively (P = 0.0036). Multivariate analysis indicated that a preoperative serum CEA level of ≥2.5 ng/ml was an independent prognostic factor. Similar results were found in patients with adenocarcinoma but not found in others.ConclusionNSCLC patients with a high serum CEA level, especially adenocarcinoma patients, had poorer prognosis even if their serum CEA levels were within the normal upper limit.

Goblet Cell Hyperplasia in the Airway of Nippostrongylus brasiliensis-Infected Rats

Background: In rats, the intestinal parasite Nippostrongylus brasiliensis is recognized as a strong inducer of intestinal goblet cell hyperplasia. Although this parasite migrates through the airways during the course of its infection, airway goblet cell response remains unknown. Objective: This study was designed to examine airway goblet cell response during the course of N. brasiliensis infection in rats and to characterize these goblet cells. Methods: Airway goblet cells were stained with Alcian blue and periodic acid-Schiff. To characterize the goblet cells, mebendazole treatment, lectin histochemistry, and RNA blot analysis using probes for rat MUC2 and trefoil peptides were examined. Results: Airway and small intestinal goblet cell hyperplasia were observed at days 14 and 21 after infection but not at day 7. In rats treated with mebendazole, goblet cell hyperplasia was not present in the small intestine, but was observed in the lung on day 14. These results indicate that airway goblet cell hyperplasia may be induced by local pulmonary factors. By lectin histochemistry, the stainability of airway goblet cells at day 21 was similar to that of small intestine goblet cells even though rat MUC2 and trefoil peptide mRNA were not detected in the lung. Conclusions: Airway goblet cell hyperplasia observed at days 14 and 21 after N. brasiliensis infection may be induced by local factors. Airway goblet cells have characteristics that differ from those of the small intestine.

Immunohistochemical demonstration of inter-alpha-trypsin inhibitor light chain (bikunin) in human mast cells.

Abstract We recently reported that the rat mast cell proteinase inhibitor trypstatin is genetically identical with the second half of inter-α-trypsin inhibitor light chain (ITI-LC), also known as bikunin or urinary trypsin inhibitor (UTI). In this study, therefore, immunoreactivities of mast cells of various human tissues were examined with three antibodies, anti-human ITI-LC, anti-ITI, which recognizes mainly heavy chains or the sugar moiety of ITI, and anti-α 1-microglobulin (α1mG). ITI-LC immunoreactivity was strongly found in mast cells in the connective tissues of various organs except for those of the propria mucosae of small intestine. Neither anti-ITI antibody nor anti-α1mG antibody reacted with mast cells in various tissues. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, α1mG/ITI-LC mRNA was not detected in the skin and tongue, and only weakly in small intestine, although ITI-LC immunoreactivity was strongly detected in these tissues. Furthermore, the mRNA was not expressed in cultured human mast cells. These results suggest that ITI-LC protein is stored in the granules of human connective tissue mast cells, though is not produced by them.

Vascular endothelial growth factor expression in pN2 non-small cell lung cancer: Lack of prognostic value

Objective:  Although several previous studies have investigated the prognostic significance of vascular endothelial growth factor (VEGF) expression in non‐small cell lung (NSCL) cancer, no previous study has concentrated on NSCL cancer with pathologically abnormal mediastinal nodes (pN2).

Distribution of Mast Cells in Mediastinal Lymph Nodes from Lung Cancer Patients

BackgroundMast cells have been documented to have several key functions with regards to malignant neoplasms. However, the functional significance of their accumulation is largely unknown. An analysis of the mast cell profile in mediastinal lymph nodes from lung cancer patients is reported here.MethodsOne hundred thirty-four, randomly selected lymph nodes (63 with positive pathological lymph node status) from 39 surgically treated lung cancer patients were examined. All cancer negative nodes were obtained from stage I patients. Mast cells were stained with Alcian blue and safranin O. Metastatic cancer cells were stained using anti-cytokeratin antibody.ResultsImmunohistochemical studies with cytokeratin revealed micro metastasis in 9/71 (12.68%) nodes previously diagnosed as histological negative. In tumor-free mediastinal lymph nodes, the mast cell count was significantly higher than in metastatic nodes. In all cases, mast cells were observed primarily in the T-cell area.ConclusionsAn inverse relationship was observed between the number of mast cells and the amount of tumor tissue. The presence of mast cells primarily in the T-cell area implies a relationship between mast cells and the T-cell system. From the present study it is not possible to conclude whether mast cells in lymph nodes are for or against tumor spread.