Mio Li

Prognostic Significance of Apoptotic Index in Completely Resected Non–Small-Cell Lung Cancer

PURPOSE To evaluate the significance of apoptotic index (AI) as a prognostic factor after surgery for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS A total of 236 patients who underwent surgery for previously untreated pathologic stage I to IIIa NSCLC between 1985 and 1990 were reviewed. AI was defined as the number of apoptotic cells, detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling, per 1,000 tumor cells. Proliferative index (PI) and aberrant p53 expression were also evaluated immunohistochemically. RESULTS The 5-year survival rate for the lowest-AI group (AI < 5.0) was 74.7%; those for the lower-AI group (5.0 < or = AI < 11.0) and the higher-AI group (11.0 < or = AI < 25.0) were 51.6% and 57.8%, respectively. These survival rates were significantly lower than that of the lowest-AI group (P =.021 and P =.043, respectively). The highest-AI group (25.0 < or = AI), however, showed the most favorable prognosis, with a 5-year survival rate of 83.2%. Multivariate analysis confirmed that a moderate AI (5.0 < or = AI < 11.0 or 11.0 < or = AI < 25.0) was a significant factor to predict poor prognosis. The PIs for the lowest-, the lower-, the higher-, and the highest-AI groups were 32.3%, 48.0%, 54.3%, and 50.7%, respectively. The lowest-AI group showed a favorable prognosis because of its low PI, whereas the lower- and the higher-AI groups had a poor prognosis caused by increased cancer-cell proliferation. The highest-AI group showed the most favorable prognosis because apoptotic cell death overcame cell proliferation. No significant correlation was observed between AI and aberrant p53 expression. CONCLUSION AI proved to be an independent prognostic factor in NSCLC.

Correlation between apoptotic index and angiogenesis in non-small cell lung cancer: comparison between CD105 and CD34 as a marker of angiogenesis.

Only a few clinical studies have documented a significant correlation between intratumoral microvessel density (IMVD), a measurement of angiogenesis, and apoptotic index (AI), an incidence of apoptosis, although many experimental studies have confirmed that insufficient angiogenesis induces accelerated apoptotic cell death. In the present study, therefore, to assess AI in correlation with IMVD in resected non-small cell lung cancer, a total of 236 patients with pathologic stage I to IIIa were reviewed. IMVDs were determined immunohistochemically with an antibody against a pan-endothelial marker, CD34 (CD34-IMVD), and an antibody against a proliferation-related endothelial marker, CD105 (CD105-IMVD). AI was defined as the number of tumor cells positive for the terminal deoxynucleotidyl tranferase-mediated dUTP-biotin nick end-labeling staining per 1000 tumor cells. When CD34 was used as a marker of angiogenesis, the mean AIs for the lower-IMVD and the higher-IMVD patients were 20.1 and 17.5, respectively, demonstrating no significant difference between the lower- and the higher-IMVD patients. In contrast, when CD105 was used, the mean AI for the lower-IMVD patients was significantly higher than that for the higher-IMVD patients (22.0 and 15.6, respectively; P=0.019). There was no significant correlation between proliferative activity and CD34-IMVD or CD105-IMVD. These results demonstrated that that decreased angiogenesis may induce enhanced apoptotic tumor-cell death without affecting cell proliferation.

Apoptosis and p53 status predict the efficacy of postoperative administration of UFT in non-small cell lung cancer

To examine whether efficacy of postoperative oral administration of UFT, a 5-fluorouracil derivative chemotherapeutic agent, may be influenced by incidence of apoptosis (apoptosis index) or apoptosis-related gene status (p53 and bcl-2) of the tumour, a total of 162 patients with pathologic stage I non-small cell lung cancer were retrospectively reviewed. UFT was administrated postoperatively to 44 patients (UFT group), and not to the other 118 patients (Control group). For all patients, 5-year survival rate of the UFT group (79.9%) seemed higher than that of the Control group (69.8%), although without significant difference (P=0.054). For patients with higher apoptotic index, 5-year survival rate of the UFT group (83.3%) was significantly higher than that of the Control group (67.6%, P=0.039); for patients with lower apoptotic index, however, there was no difference in the prognosis between these two groups. Similarly, UFT was effective for patients without p53 aberrant expression (5-year survival rates: 95.2% for the UFT group and 74.3% for the Control group, P=0.022), whereas not effective for patients with p53 aberrant expression. Bcl-2 status did not influence the efficacy of UFT. In conclusion, apoptotic index and p53 status are useful factors to predict the efficacy of postoperative adjuvant therapy using UFT.

Primary lung carcinoma arising from emphysematous bullae

To clarify clinical characteristics and biological features of primary lung carcinoma arising from emphysematous bullae (EB), a total of 50 patients (49 males and one female) among all 1478 patients who underwent operation for primary lung carcinoma cases were reviewed; biological features were examined in 31 patients whose resected specimens were available for immunohistochemical staining (IHS). Thirty-one patients (62.0%) had pathologic stage I disease, and 30 cases (60.0%) had poorly differentiated tumor, demonstrating earlier pathologic stages and poorer cell differentiation of lung carcinoma with EB as compared with that without EB. The mean proliferative index (PI) for carcinoma with EB was 64.0%, which was significantly higher than that for carcinoma without EB (47.2%, P = 0.001); no significant difference in Apoptotic index (AI) was demonstrated. Aberrant p53 expression was less frequent in carcinoma with EB (29.0%) than in carcinoma without EB (47.9%, P = 0.043). Five-year survival rates for carcinoma with and that without EB were 50.3 and 46.9%, respectively, showing no significant difference. Multivariate analysis did not demonstrate that association of EB was a significant prognostic factor. In conclusion, although with the poorer cell differentiation and accelerated proliferative activity of lung carcinoma arising from EB, this does not have a significantly different prognosis than primary lung carcinoma not associated with bullae.

Biological features and preoperative evaluation of mediastinal nodal status in non–small cell lung cancer

BACKGROUND To examine whether biological features of primary tumor can help preoperative evaluation of mediastinal nodal status in non-small cell lung cancer. METHODS A total of 450 patients who underwent tumor resection and mediastinal dissection were reviewed. p53 status and proliferative fraction (PI) were evaluated immunohistochemically. RESULTS The accuracy of preoperative evaluation of mediastinal nodal status with computed tomography (CT) was 72.2%; mediastinal nodal metastases had not been revealed until operation in 59 patients (13.1%) (false-negative), and no metastasis was revealed in 66 patients (14.7%) although mediastinal nodal enlargement had been demonstrated by CT (false-positive). The number of false-negative patients was significantly larger when p53 aberrant expression was positive or when PI was higher. Combined with p53 status and PI, there were 27 false-negatives (24.1%) among patients with aberrant p53 expression and higher PI, whereas only two false-negatives (1.5%) among those with negative p53 expression and lower PI. CONCLUSIONS Mediastinoscopy may be recommended for tumor showing aberrant p53 expression and higher PI, even when CT demonstrates no mediastinal nodal enlargement.

Parasternal lymph node metastasis of malignant peritoneal mesothelioma: report of a case.

We report a case of malignant peritoneal mesothelioma with parasternal lymph node metastasis. The patient was a 34-year-old man who presented with a history of several years of abdominal pain and ascites of unknown origin. Exploratory laparoscopic biopsies yielded histological findings of malignancy, but a final diagnosis was not able to be made. A chest computed tomographic scan done the following year showed a parasternal nodule, and thoracoscopically obtained biopsied material was positive for calretinin. These findings led to a pathological diagnosis of metastasis to the parasternal lymph node from peritoneal mesothelioma.

Solitary Atypical Adenomatous Hyperplasia in the Lung of a 17-Year-Old Man with Spontaneous Pneumothorax

We report here a case of solitary atypical adenomatous hyperplasia (AAH). A 17-year-old non-smoker man developed spontaneous pneumothorax, and computed tomogram scanning of his chest revealed a ground-glass opacity measuring 5 × 5 mm in the right lung with no change in its size for the next 7 months. To exclude the possibility of pulmonary neoplasia, he underwent partial pulmonary resection. The postoperative pathologic diagnosis was AAH. The present case is very exceptional for AAH because of the patient’s young age and non-association with pulmonary carcinoma. The postoperative 23-month follow-up was uneventful.

A pitfall of CT findings in peripheral lung adenocarcinoma.

We describe a case of lung adenocarcinoma that appeared to be 2 cm distal from the pleural surface in a preoperative CT examination but was located just below the pleura and showed direct pleural invasion at thoracotomy. This discrepancy was caused by compensatory expansion of adjacent lung tissue, which filled the dead space between the tumor with retracted visceral pleura and intact parietal pleura. The clue used to identify this condition is the flat outer configuration of the tumor. To avoid underestimating the stage of lung cancer patients, we emphasize the importance of careful evaluation of pleural indentation and tumor configuration in CT studies.