Seiki Kobayashi

Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells

Expression of the transcription factor FOXP3 characterizes regulatory T cells (Tregs) that engage in the maintenance of immunological self-tolerance and immune homeostasis. Intra-tumoral accumulation of Tregs is associated with unfavorable prognosis in several kinds of cancers. Recently, expression of FOXP3 and its association with prognosis have also been shown in some cancer cells in clinical studies. For non-small cell lung cancer (NSCLC), however, prognostic significance of tumor FOXP3 expression and its relationship with Tregs remain unknown. FOXP3 expression in cancer cells and tumor-infiltrating lymphocytes was examined by immunohistochemical staining of surgical specimens from 87 patients with NSCLC. Prognostic values of the tumor-infiltrating Treg count and tumor FOXP3 expression status were evaluated retrospectively. FOXP3-positive cancer cells were observed in 27 of 87 (31.0%) patients. There was no significant relationship between Treg count and tumor FOXP3 status. Increased Treg counts were associated with worse overall and relapse-free survival whereas the influence of tumor FOXP3 status on survival was not significant. However, when FOXP3-positive cancer cells were present, the relationship between Treg accumulation and worse prognosis was attenuated. In contrast, patients without tumor FOXP3 expression and high Treg count had significantly worse overall and relapse-free survival (hazard ratio: 3.118 and 3.325, p=0.028 and 0.024, respectively) than other groups. These results suggest that tumor FOXP3 expression has a better prognostic potential in NSCLC and that in combination with tumor-infiltrating Treg count the absence of tumor FOXP3 allows the selection of high-risk patients.

Long-term prognosis of video-assisted limited surgery for early lung cancer §

OBJECTIVE The present intervention study was conducted to prospectively evaluate the long-term prognosis for video-assisted limited surgery, such as wedge resection and segmentectomy, for clinically early lung cancers depending on findings in high-resolution computed tomography (HRCT). SUBJECTS AND METHODS Patients were enrolled in the study between 2001 and 2004, and followed up for five subsequent years. Of these patients, those with a clinical stage IA lung cancer mainly comprising a ground glass-opacity (GGO) less than 1.5 cm across underwent thoracoscopic wedge resection of the lung (Group A). Patients with a tumour less than 2.0 cm in diameter, not classified in Group A, underwent video-assisted segmentectomy and hilar lymph node dissection with lobe-specific mediastinal nodes sampling (Group B). For patients with a tumour less than 3.0 cm in diameter, not classified in to any of the foregoing two groups, underwent video-assisted lobectomy and hilar and mediastinal lymph node dissection (Group C). RESULTS During the case registration period, 159 patients were registered for enrollment in the study (21 for Group A, 43 for Group B and 95 for Group C). Of the patients in Groups A and B, 28% were shifted to a surgical procedure involving a larger volume resected; 6% of the entire study population were shifted to thoracotomy. All patients completed the 5-year follow-up. The recurrence-free survival rate was 100% for Group A, 90.5% for Group B and 94.5% for Group C, with no significant difference among the groups. The total recurrence rate was 11.9% with localised recurrences observed in 6.3% of the patients and remote recurrences in 5.7%. The localised recurrences observed included stump recurrence in one case of Group B, and malignant pleural effusions/pleural dissemination in two cases of Group B and one case of Group C. Intrathoracic lymph node recurrences were observed in one case of Group B and five cases of Group C. CONCLUSIONS The present intervention study showed that thoracoscopic-limited surgery for clinically early lung cancers depending on findings in preoperative HRCT is feasible and appropriate from the viewpoint of oncology.

Usefulness of sentinel lymph node biopsy for the detection of lymph node micrometastasis in early lung cancer

The purposes of this study were to examine the usefulness of the biopsy of the sentinel lymph nodes (SNs) for the accurate and effective detection of lymph node micrometastasis in early lung cancer and to clarify the spread of lymph node micrometastasis. One hundred and thirty-three c-stage IA non-small cell lung cancer patients in whom SNs could be identified by radioisotope (RI) method were enrolled. All dissected lymph nodes were stained with cytokeratin AE1/AE3 for the examination of micrometastasis. A total of 1375 lymph nodes including 220 SNs were dissected from the 133 patients. From the 220 SNs, 35 (15.9%) were found to be positive for metastasis. Of the other 185 SNs negative for metastasis, 19 (8.6%) were positive for micrometastasis. When patients were limited to those with pN0, there were no lymph nodes positive for micrometastasis other than SNs. In pN1-2 patients, micrometastasis to non-SNs were observed in 2.3-13.2%. In patients with pN0, micrometastasis was limited to SNs, and the results of the examination of SNs for micrometastasis accurately represented those of the examination of all lymph nodes. With advancement of the stage, micrometastasis was not limited to SNs and showed an irregular distribution.