Molecular biological markers and micrometastasis in resected non-small-cell lung cancer. Prognostic implications.

OBJECTIVES: Recent advances in molecular biology and genetics have created new diagnostic and treatment possibilities in clinical oncology. We evaluated the usefulness of molecular biological factors in primary tumor and micrometastasis in the bone marrow and pathological negative (pN0) lymph nodes as prognostic parameters in non-small-cell lung cancer (NSCLC) patients. METHODS: Pathological specimens were collected from 129 NSCLC patients to analyze molecular biological markers, including K-ras, p53, Rb, p16, loss of heterozygosity (LOH) at 3p, vascular endothelial growth factor (VEGF), and telomerase activity. Bone marrow samples from 250 NSCLC patients and pN0 lymph nodes from 85 of these patients were collected for micrometastasis detection by immunohistochemistry against cytokeratin. RESULTS: p53 abnormalities and 3p LOH were significantly associated with reduced patient survival in adenocarcinoma, whereas VEGF expression was significantly associated with reduced survival in a squamous cell carcinoma histological subtype by univariate or multivariate analysis. We identified micrometastatic tumor cells in bone marrow of 78 (31.2%) of 250 patients and in pN0 lymph nodes of 26 (30.6%) of 85 patients. Both bone marrow and lymph nodal micrometastases were associated with decreased survival among patients with stage I, however, only lymph nodal micrometastasis had a significant impact on survival. CONCLUSIONS: Molecular biological features of primary tumor and micrometastatic status appear useful in defining groups of patients with a poor prognosis who could benefit from adjuvant systemic treatment.

Peripheral lung adenocarcinoma: correlation of thin-section CT findings with histologic prognostic factors and survival.

PURPOSE: To evaluate the prognostic importance of thin-section computed tomographic (CT) findings of peripheral lung adenocarcinomas. MATERIALS AND METHODS: The subjects were 127 patients with adenocarcinomas smaller than 3 cm in largest diameter who underwent at least a lobectomy with hilar and mediastinal lymphadenectomy. The margin characteristics of nodules and the extent of ground-glass opacity (GGO) within the nodules at preoperative thin-section CT were analyzed retrospectively. Regional lymph node metastasis (LNM) and vessel invasion (VI) were histologically examined in surgical specimens. Survival curves were calculated according to the Kaplan-Meier method. RESULTS: The frequencies of LNM (4% [1 of 24]) and VI (13% [three of 24]) in adenocarcinomas with GGO components of more than 50% were significantly lower than those with GGO components of less than 10% (LNM, P <.05; VI, P <.01). The patients with GGO components of more than 50% showed a significantly better prognosis than those with GGO components less than 50% (P <.05). All 17 adenocarcinomas smaller than 2 cm with GGO components of more than 50% were free of LNM and VI, and all these patients are alive without recurrence. Coarse spiculation and thickening of bronchovascular bundles around the tumors were observed more frequently in tumors with LNM or VI than in those without LNM or VI (P <.01). CONCLUSION: Thin-section CT findings of peripheral lung adenocarcinomas correlate well with histologic prognostic factors.

Generation of autologous tumor-specific T cell clones from a patient with adenosquamous carcinoma of the lung.

BACKGROUND: Adenosquamous carcinoma of the lung is not a common cancer, but its prognosis is worse than that of adenocarcinoma or squamous cell carcinoma. Therefore, new therapeutic strategies need to be developed to treat this type of lung cancer. Recently, vaccination using tumor antigens which are recognized by cytotoxic T lymphocytes (CTL) has been applied mainly to melanoma patients. We therefore attempted to establish T cell clones specific for autologous tumor cells (AT) from a patient with adenosquamous carcinoma in order to analyze the specific immune responses against AT. METHODS: A lung adenosquamous carcinoma cell line was established from a resected tumor obtained from a 72-year-old patient. Regional lymph node lymphocytes were stimulated weekly with CD80-transfected AT to induce CTL. The CTL activities were assessed by a standard (51)Cr release assay and by cytokine release. RESULTS: We succeeded in inducing an AT-specific CTL line. Using a limiting dilution method, eight T cell clones were established. AT-specific activity was observed in three CD8(+) T cell clones and one CD4(+) T cell clone out of the eight clones tested. Anti-HLA class I and anti-HLA-B/C mAbs inhibited IFN-gamma production from the AT-specific CD8(+) clones co-cultured with AT, thus indicating the restriction element to be HLA-B*5201 or HLA-Cw*1202. In contrast, the CD4(+) T cell clone recognized AT in an HLA class II-restricted manner. CONCLUSIONS: These results are the first demonstration of a successful induction of AT-specific T cell clones from a patient with lung adenosquamous carcinoma. It may therefore supply a possible way to apply specific immunotherapy to this type of lung cancer.

Pleural retraction and intra-tumoral air-bronchogram as prognostic factors for stage I pulmonary adenocarcinoma following complete resection.

BACKGROUND AND OBJECTIVES: We have retrospectively analyzed the postoperative prognostic factors for 116 patients with stage I adenocarcinoma, with special reference to pleural retraction and intra-tumoral air-bronchogram imaged by computed tomography, which may represent the biological features of pulmonary adenocarcinoma for the retraction of surrounding tissues due to central necrosis and air space-lining growth, respectively. METHODS: The subgroups divided according to the presence of pleural retraction and/or intra-tumoral air-bronchogram on pre-operative CT were compared with respect to the postoperative disease-free survival (DFS) and other clinico-pathological factors. RESULTS: The rates of DFS at 5 years associated with 61 patients with pleural retraction and with 55 patients without pleural retraction were 64.4% and 91.3%, respectively (P = 0.0052), and those associated with 83 patients with air-bronchogram-positive tumors and with 33 patients with air-bronchogram-negative tumors were 81.8% and 64.8%, respectively (P = 0.0040). The DFS at 5 years associated with T1 (73 patients) and T2 (43 patients) were 83.6% and 64.3%, respectively (P = 0.0153). The Cox proportional hazards model analysis revealed that the presence of pleural retraction and the absence of air-bronchogram were independent factors for poor prognosis with relative risks of 7.8 and 5.1, respectively. Pathological T factor was also a significant prognostic factor with a relative risk of 3.2. Seventeen patients with pleural retraction-positive and air-bronchogram-negative tumors showed the high recurrence rate of 47.5% and a poor prognosis with DFS at 5 years of 35.1%. CONCLUSION: These results suggested that, in stage I adenocarcinoma, the degree of malignant potential may be well figured by radiological imaging, with a significant affect on susceptibility of recurrence following complete resection.

Evaluations of p53 immunoreactivity, nucleolar organizer regions, and proliferating cell nuclear antigen in non-small cell lung carcinoma.

We examined p53 protein expression, proliferating cell nuclear antigen (PCNA), and argyrophilic nuclear organizer regions (AgNOR), in 102 patients with surgically-treated non-small cell lung cancer (NSCLC). p53 positive cases with DO-1 were defined when more than 10% of the tumor cell nuclei were stained. Mean AgNOR count and PCNA LI were 2.80 and 40.7 and there were no significant differences of AgNOR count and PCNA LI between p53 positive and negative cases. We assessed the relationship between the p53 immunoreactivity and various clinical or pathological parameters. p53 positive rate of stage III disease (46.3%) was significantly higher than that of stage II disease (28.6%). The p53 positive rate of squamous cell carcinoma (42.1%) tended to be higher than that of adenocarcinoma (33.9%). In the survival curves of patients with NSCLC according to the p53 immunoreactivity, there was no significant difference between p53 positive and negative cases. Eight potential prognostic parameters (p53 immunoreactivity, AgNOR count, PCNA LI, sex, age, year of operation, histology, and stage) were also estimated, using univariate and multivariate analysis. In univariate analysis, PCNA LI and AgNOR count, and stage were significantly related to shortened survival. In multivariate analysis, PCNA LI, Age, and stage were independently associated with shortened survival of NSCLC patients. PCNA staining may be more useful than p53 and AgNOR staining in assessing the aggressiveness of surgically-treated NSCLC, although the most useful clinical prognostic parameter should be achieved by the combined analysis of several prognostic indicators.

Bone metastasis after a resection of stage I and II primary lung cancer.

In the present study, we reviewed the patients who developed bone metastases after a surgical resection of primary lung cancer and evaluated their clinicopathological features. From 1992 to 1995, 177 patients with stage I and II primary lung cancer underwent a surgical resection at the Kitakyushu Municipal Medical Center. Bone metastases were detected in 14 patients (7.9%) by follow-up examinations including bone scintigraphy (scan). Bone metastasis was one of the most frequent extra-thoracic recurrent forms. Patients with adenocarcinoma tended to develop bone metastases more frequently than those with squamous cell carcinoma. In the preoperative bone scans, an abnormal uptake was observed in 76 patients (42.9%), and 10 (13.1%) of them were found to develop bone metastases in the follow-up studies. A microscopic examination of the primary tumor demonstrated close correlation between intratumoral and peritumoral lymphatic vessel invasion and postoperative development of bone metastases. A bone scan is a very useful and indispensable procedure for diagnosing bone metastases. However, this scan may also show false positive finding in a number of benign conditions. Therefore, a surgical resection should be considered as the first-line treatment for patients with positive findings in the bone scan when the diagnosis of bone metastasis can not be confirmed based on both their symptoms and other clinical examinations.

Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the lung.

The expression of matrix metalloproteinase-2 (MMP-2; 72 kDa type IV collagenase/gelatinase A) and MMP-9 (92 kDa type IV collagenase/gelatinase B) was immunohistochemically investigated in 79 T1 adenocarcinomas of the lung using non-commercial polyclonal anti-MMP-2 and -9 antibodies. Thirty-two (41%) and 22 (28%) among the 79 cases were positive in the tumor cells for MMP-2 and -9, respectively. The incidences of MMP-2 and -9 immunoreactivities were higher (64 and 45%, respectively) in poorly differentiated tumors than in well differentiated tumors (36 and 25%, respectively), and lower in bronchioloalveolar carcinoma (22 and 10%, respectively) compared with other subtypes of adenocarcinoma. The prognosis for patients with MMP-2 and/or -9 positive immunoreactivities was significantly poorer than for those with a MMP-negative tumor (P < 0.05). The degree of collagenization was divided into four grades, and tumors with a small to abundant amount of collagen (grade 2 and grade 3 fibrosis) had a higher incidence of immunoreactivity to both types of MMP. It is estimated that these expressions might be responsible for tumor invasion, metastasis, and for grade 2 and grade 3 fibrosis in T1 adenocarcinoma of the lung.

[Treatment with expandable metallic stent in patients with carcinomatous airway stenosis--evaluation of patient's quality of life].

The expandable metallic stent was used in 10 patients with carcinomatous airway stenosis. In all patients, the respiratory symptoms improved immediately after insertion of the stent. Eight of the 10 patients, performance status improved. Totally, the use of expandable metallic stent improved the quality of life for patients with carcinomatous airway stenosis. Complication was minimal. We conclude that expandable metallic stent for treatment of carcinomatous airway stenosis are useful in emergent cases.

Lymphangioma of the oesophagus: a case report and review of the literature.

Lymphangioma of the oesophagus is exceedingly rare. Seven cases (including our present case) have been reported in the world and are reviewed.

Surgical resection for pulmonary metastases of sweat gland carcinoma.

A case of axillary sweat gland carcinoma which metastasised to both lungs six years after resection of the primary lesion is described. The lesions were resected and three years later two further pulmonary metastases were resected.

A clinicopathological evaluation of nucleolar organizer region proteins in human breast carcinoma.

The number of nucleolar organizer region proteins (NORs) identified by silver staining (Ag) was studied in 106 primary breast carcinomas. The AgNOR score (mean +/- SD) in tumours smaller than 2 cm was significantly lower than that in tumours larger than 2 cm (P < 0.05). However, there was no significant difference according to other clinicopathological characteristics. According to postoperative distant recurrence, the AgNOR count was significantly higher in the group with recurrence than in the group without recurrence (P < 0.05). Further, the survival rate was significantly lower in the high AgNOR score (> or = 3) group than in the low score (< 3) group (P < 0.01). The present study indicates that the AgNOR score in human breast cancer cells is useful for evaluating cell proliferative activity and may help predict postoperative distant recurrence and, ultimately, the postoperative prognosis of patients.

Foreign-body granuloma mimicking an extrahepatically growing liver tumor: report of a case.

We herein describe a 74-year-old woman with a foreign-body granuloma mimicking a liver tumor. Imaging studies revealed a pedunculated left lobe mass in the setting of chronic liver disease. She had a past history of a cholecystectomy as well as a previous gynecological operation. A left lateral segmentectomy was performed because of the possibility of a rupture. The dissected specimen showed a foreign-body granuloma caused by gauze. We believe this case to be a very unique granuloma, which should be kept in mind whenever making a diagnosis of a liver tumor particularly in a patient with chronic liver disease, who has a past history of abdominal surgery.

Surgical treatment of lung cancer in the octogenarian.

The purpose of this study was to investigate the value of surgical treatment for lung cancer in the octogenarian. Thirty-three patients 80 years of age or older (mean age, 82.4; range, 80 to 92 years; 25 men, 8 women) underwent surgical resection in our units between 1974 and 1991. The operative mortality rate was 3%, and the 5-year survival rate was 32%. The relative 5-year survival rate (survival rate of our subjects/that of matched population) was 61%. The mortality and long-term survival rates were similar to those in younger patients. In this study, long-term survival had no significant dependence on stage of disease, histologic tumor type, or complete versus incomplete resection. It was dependent mainly on postoperative complications, in particular, cardiorespiratory complications (cardiac complications, p = 0.0005; respiratory complications, p < 0.05). These data suggest that the octogenarian who suffers from lung cancer deserves the opportunity for a cure and the long-term benefits of surgical treatment, on the condition that no postoperative major cardiorespiratory complications set in.

[Two cases of pulmonary lymphangioleiomyomatosis].

We report two cases of pulmonary lymphangioleiomyomatosis with recurrent spontaneous pneumothorax. The cases were diagnosed by open lung biopsy. Case 1 was a 38-year-old woman, whose chest X-ray showed linear and reticular shadows. Lung tissue was negative for hormone receptors. She was treated with tamoxifen, but developed allergic symptoms. Her condition gradually deteriorated despite oxygen and progesterone therapy. Case 2 was a 41-year-old woman, whose chest X-ray showed a reticular shadows and slight overinflation. Hormone receptors were not examined, but the disease did not progress with oxygen, progesterone and GnRH agonist (Sprecur) therapy.