• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.23-28
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• 1993

Background: Since an important component of carcinogenesis is unregulated growth, many investigators have reported the methods to detect cell proliferation in tissues including PCNA. PCNA is a 36 Kd intranuclear polypeptide and plays a critical role in cell proliferation. Thus progressive dysregulation of proliferation during carcinogenesis can be directly visualized in the paraffin embedded tissue using immunohistochemistry for PCNA which has an advantage of simplicity and maintenance of tissue architecture. The heterogeneity of PCNA expression is known to be related with proliferating fraction, histologic grade, DNA ploidy, and susceptibility of anticancer drugs, etc. We analyzed the biologic significance of the expression of PCNA in lung cancer tissues. Method: 43 lung cancer tissues, which were resected by surgery and were embedded in paraffin, were stained immunohistochemically by one hour MicroProbe System and the results were corelated with cell type, stage, site and survival. Result: 1) Suamous cell type showed high positivity (89%) than in adenocarcinoma (54%). 2) No significant difference related to tumor stage was noticed. 3) No significant difference between primary site and metastatic site was noticed. 4) No significant difference in 12-month survival between positive group and negative group was noticed. Conclusion: From this study, we concluded that imunohistochemistry for PCNA expression of routinely processed tissue is a simple technique for the assessment of proliferation in non-small cell lung cancer. Whether the labelling index has an independent prognostic value and deserves special attention in pathobiological evaluation in lung cancer remains to be investigated from large series with longer follow-up and to be correlated with multiple biological markers.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.177-183
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• 2004

Purpose: Authors would report the results of sequential CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, and prednisone) and involved field radiotherapy (IFRT) for early stage nasal natural killer/T-cell Iymphoma (NKTCL). Materials and Methods: Fourteen among 17 patients, who were registered at the Samsung Medical Center tumor registry with stage I and II nasal NKTCL from March 1995 to December 1999 received this treatment protocol. Three to four cycles of CHOP chemotherapy were given at 3 weeks' interval, which was followed by local IFRT including the known tumor extent and the adjacent draining lymphatics. Results: Favorable responses after chemotherapy (before IFRT) were achievable only in seven patients (5 CR's+2 PR's: 50%), while seven patients showed disease progression. There were six patients with local failures, two with distant relapses, and none with regional lymphatic failure. The actuarial overall survival and progression-free survival at 3 years were 50.0% and 42.9%. All the failures and deaths occurred within 13 months of the treatment start. The factors that correlated with the improved survival were the absence of 'B' symptoms, the favorable response to chemotherapy and overall treatment, and the low risk by international prognostic index on univariate analyses. Conclusion: Compared with the historic treatment results by IFRT either alone or followed by chemotherapy, the current trial failed to demonstrate advantages with respect to the failure pattern and survival. Development of new treatment strategy in combining IFRT and chemotherapy is required for improving outcomes.