Presence of podoplanin-positive cancer-associated fibroblasts in surgically resected primary lung adenocarcinoma predicts a shorter progression-free survival period in patients with recurrences who received platinum-based chemotherapy.

PURPOSE: The influence of microenvironmental factors on the effectiveness of chemotherapy is being increasingly recognized. The purpose of this study was to investigate the relationships between cancer cell and stromal cell phenotypes in primary tumors and the progression-free survival (PFS) of recurrent lung cancer patients who received platinum-based chemotherapy. METHODS: We retrospectively analyzed 87 postoperative recurrent lung adenocarcinoma patients treated with platinum-based chemotherapy. The expressions of drug resistance-related proteins including BCRP, ezrin, and ALDH1 in cancer cells, the number of CD204-positive tumor-associated macrophages (TAMs), and the presence of podoplanin-positive cancer-associated fibroblasts (CAFs) in the primary tumor were examined. The relationships between the immunohistochemical staining results of primary tumors and the PFS after receiving chemotherapy were also analyzed. RESULTS: Among the clinicopathological factors of primary tumors, only an advanced pathological stage was significantly associated with a shorter PFS. As for immunohistochemical staining, no significant relationships were found between the PFS and the expression of BCRP, ezrin, or ALDH1. Although the number of CD204-positive TAMs was not associated with the PFS, the presence of podoplanin-positive CAFs was significantly associated with a shorter PFS (median PFS: 5.1 vs. 7.8 months, P = 0.028). A multivariate analysis revealed a tendency of podoplanin-positive CAFs to be correlated with a shorter PFS (P = 0.087). CONCLUSIONS: The presence of podoplanin-positive CAFs in the primary tumor could be a predictor of a shorter PFS in recurrent lung adenocarcinoma patients who received chemotherapy. These findings suggest that stromal-cell-derived factors should be incorporated into predictions of the effectiveness of chemotherapy.

[Synchronous appearance and improvement with anticancer chemotherapy of paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome complicated with small cell lung cancer].

A 62-year-old man who had suffered from instability of gait and double vision for two months was admitted to our hospital because of weakness of the extremities and ataxia of the extremities and trunk. Chest X-rays and CT scans showed enlargement of the left hilar lymph nodes and a nodular shadow in the left lung. Transbronchial biopsy revealed small cell lung cancer. We diagnosed the patient with two conditions: paraneoplastic cerebellar degeneration (PCD), based on cerebellar ataxia, the presence of Hu antineuronal antibodies, and the absence of cerebellar atrophy and malignancy; and Lambert-Eaton myasthenic syndrome (LEMS), based on weakness of the extremities, the presence of P/Q-type voltage-gated calcium channel antibodies, and waxing in the evoked electromyogram. Anticancer chemoradiation therapy that was started within three months of symptom onset resulted in reductions in size of the hilar lymph nodes and the nodule. Concurrently, cerebellar ataxia, weakness of the extremities, and double vision all disappeared. Anticancer chemotherapy is effective against LEMS while usually less effective against PCD. Early commencement of anticancer chemotherapy is recommended for the treatment of PCD with LEMS.