Takanori Ayabe

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.

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.

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).

Immunohistochemical analysis of nm23-H1 gene product in node-positive lung cancer and lymph nodes

The nm23-H1 gene product has been considered as an anti-metastatic protein and the level of its expression has been reported to correlate inversely with metastatic potential in some cancers. However, the expression of nm23-H1 gene product in the metastatic sites have not been studied in detail. We examined the expression of nm23-H1 gene product in surgically resected 46 pairs of primary lung cancers and metastatic lymph nodes by immunohistochemistry. The positive staining of nm23-H1 gene product in primary cancers and metastatic lymph nodes were observed in 56.5 and 67.4%, respectively. The heterogeneity of nm23-H1 gene product expression between primary cancers and metastatic lymph nodes was observed in 41.3%. No correlations were found between the nm23-H1 gene product expression in lung cancers and the patients survival. No significant association was also observed between nm23-H1 gene product expression in lymph nodes and the patients survival. There was, furthermore, no correlation between the heterogeneity of nm23-H1 gene product expression and the patients survival. In conclusion, the level of nm23-H1 gene product expression does not significantly reveal prognostic value in node-positive lung cancers. Expression of nm23-H1 gene product in metastatic lymph nodes was also unrelated to patients survival.

Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival

BackgroundWe assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma.MethodsFormalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody.ResultsExpression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87).ConclusionsIn patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion.

Prognostic significance of the combined use of preoperative platelet count and serum carcinoembryonic antigen level in non-small-cell lung cancer

PurposeThe prognostic significance of the combined use of preoperative platelet count and serum carcinoembryonic antigen (CEA) level in non-small-cell lung cancer patients was investigated.MethodsConsecutive 289 non-small-cell lung cancer patients were reviewed retrospectively. Thrombocytosis was defined as a platelet count of at least 40 × 104/mm3.ResultsThe frequency of preoperative thrombocytosis was 4.5% (13/289). The 5-year survival of patients with thrombocytosis was 30.77%, which was significantly poorer than that of patients with normal counts (68.65%, P = 0.0010). The 5-year survivals of patients with a normal CEA level and those with an elevated serum CEA level were 74.18% and 55.78%, respectively (P = 0.0019). Patients with both a normal platelet count and a normal serum CEA level had a favorable prognosis, whereas those with both thrombocytosis and elevated serum CEA level had a poor prognosis. The prognostic impact of the combined use of the platelet count and the serum CEA level was more significant than that of the platelet count or the serum CEA level alone. Both univariate and multivariate analyses indicated an independent prognostic impact of the combined use of platelet count and serum CEA levels.ConclusionThe combined use of preoperative platelet count and serum CEA levels might be useful for predicting the prognosis of non-small-cell lung cancer patients.

Expression of nm23-H1 gene product in mediastinal lymph nodes from lung cancer patients

OBJECTIVE Although numerous studies have shown that nm23-H1 gene product expression is inversely related to metastatic potential in some cancers, the expression in lymph nodes has not been studied in detail. An analysis of nm23-H1 gene product expression in mediastinal lymph nodes from lung cancer patients is reported. METHODS One hundred and thirty-four, randomly selected lymph nodes (63 with positive pathological lymph node status) from 39 surgically treated lung cancer patients were examined. Expression of nm23-H1 gene product was determined using specific monoclonal antibodies. Metastatic cancer cells were highlighted using anti-cytokeratin antibody. RESULTS Expression of nm23-H1 gene product in patients with less and more than 50% nodes-positive was 12/23 (52.2%) and 15/16 (93.8%) cases, respectively. Immunohistochemical studies with cytokeratin revealed micrometastasis in 6/39 (15.4%) patients and 9/71 (12.7%) nodes previously reported as cancer negative. Expression of nm23-H1 gene product in micrometastasis and metastasis-positive nodes was 5/9 (55.6%) and 55/63 (87.3%), respectively. We also found nm23-H1 gene product expression in germinal center cells. However, we found no relationship between expression of nm23-H1 gene product in germinal center cells and extent of metastasis. CONCLUSIONS Our study demonstrates a positive relationship between expression of nm23-H1 gene product and extent of metastasis in mediastinal lymph nodes from lung cancer patients. Our data for normal germinal center cells suggests that nm23-H1 gene product expression does not play a specific biological role in suppressing tumor metastasis in lung cancer.

Impact of smoking on outcome of resected lung adenocarcinoma

ObjectiveSmoking is a well-known causative factor of lung cancer and the association of smoking with adenocarcinoma is considered to be the weakest. We investigated the influence of smoking on postoperative prognosis in patients with lung adenocarcinoma.MethodsOne hundred and eighty-one consecutive patients of resected lung adenocarcinoma were studied retrospectively. The histologic subtype was subdivided into 2 groups: lepidic dominant histologic subtype, including adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant invasive adenocarcinoma versus other subtypes.ResultsThe 5-year survival of ever smokers was significantly unfavorable than that of never smokers. Similarly, there was also a relationship between the patients’ survival and Brinkman index (BI), with unfavorable survival found in patients with greater smoking histories. Based on a multivariable analysis, pN status and BI were significant factors affecting the postoperative prognosis of patients undergoing surgery. However, gender, serum carcinoembryonic antigen (CEA) level, lepidic dominant histologic subtype and pure/mixed ground-glass opacity (GGO) were not prognostic factors although previous reports showed prognostic significance. These factors that we failed to find the prognostic significance were significantly associated with smoking.ConclusionThe smoking was significantly predictive of an unfavorable prognosis after surgery for lung adenocarcinoma. It is suggested that smoking is associated with serum CEA level, histologic subtype and GGO, resulting in unfavorable outcome.

Postoperative Serum CEA Level is a More Significant Prognostic Factor than Post/Preoperative Serum CEA Ratio in Non-small Cell Cancer Patients.

BACKGROUND In non-small cell lung cancer (NSCLC) patients with preoperative high serum carcinoembryonic antigen (CEA) level, patients with a persistently high serum CEA level after surgery have been reported to have a poor prognosis. In addition, in other cancers, the post/preoperative serum CEA ratio has been reported as a useful parameter. MATERIALS AND METHODS We enrolled 123 NSCLC patients with preoperative high CEA levels (≥ 5 ng/mL) who underwent curative surgery between 2004 and 2011. Prognostic significance of postoperative serum CEA level and the CEA ratio was examined. RESULTS The 5-year survival of patients with persistently high serum CEA level after surgery was poor. On the other hand, patients with normal postoperative serum CEA levels had significant favorable prognosis. The patients with CEA ratio>1 had poor prognosis, however the number was only 7 (5.7%). The 5-year survival rates of patients with other subgroup based on the CEA ratio (0.5 ≥ CEA ratio and 0.5 ≤ CEA ratio ≤ 1) was similar. Multivariate analysis revealed prognostic significance for the postoperative serum CEA level but not the CEA ratio. CONCLUSIONS For NSCLC patients with preoperative high serum CEA level, their postoperative serum CEA levels is a more significant prognostic factor than the post/preoperative serum CEA ratio.