Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.
The purpose of this research is to explore differences between small and medium-sized companies and large-sized companies in the impact of human resource innovativeness(HRI), learning orientation(LO), and HRI-LO interaction on innovation effect and business performance. Although learning orientation has long been considered as a key factor influencing good performance of a business, little research was devoted to exploring the effect of HRI-LO interaction on innovation effect and business performance. In this study, it is investigated whether there is a synergy effect between innovative human workforce and learning orientation corporate culture, in addition to each by itself, to generate good business performance as well as a success of new innovations in the market. Research hypotheses were as follows, including H1) human resource innovativeness(HRI), learning orientation(LO), and interactions of HRI and LO(HRI-LO interaction) positively affect innovation effect, H2) there is a difference of the effect of HRI, LO, and HRI-LO interaction on innovation effect between large-sized and small-sized companies, H3) HRI, LO, HRI-LO interaction, innovation effect positively affect business performance, and H4) there is a difference of the effect of HRI, LO, HRI-LO interaction, and innovation effect on business performance between large-sized and small-sized companies. Data were obtained from 479 practitioners through a web survey since the web survey is an efficient method to collect a national data at a variety of fields. A single respondent from a company was allowed to participate in the study after checking whether they have more than 5-year work experiences in the company. To check whether a common source bias is existed in the sample, additional data from a convenient sample of 97 companies were gathered through the traditional survey method, and were used to confirm correlations between research variables of the original sample and the additional sample. Data were divided into two groups according to company size, such as 352 small and medium-sized companies with less than 300 employees and 127 large-sized companies with 300 or more employees. Data were analyzed through t-test and regression analyses. HRI which is the innovativeness of human resources in the company was measured with 9 items assessing the innovativenss of practitioners in staff, manager, and executive-level positions. LO is the company's effort to encourage employees' development, sharing, and utilizing of knowledge through consistent learning. LO was measured by 18 items assessing commitment to learning, vision sharing, and open-mindedness. Innovation effect which assesses a success of new products/services in the market, was measured with 3 items. Business performance was measured by respondents' evaluations on profitability, sales increase, market share, and general business performance, compared to other companies in the same field. All items were measured by using 6-point Likert scales. Means of multiple items measuring a construct were used as variables based on acceptable reliability and validity. To reduce multi-collinearity problems generated on the regression analysis of interaction terms, centered data were used for HRI, LO, and Innovation effect on regression analyses. In group comparison, large-sized companies were superior on annual sales, annual net profit, the number of new products/services in the last 3 years, the number of new processes advanced in the last 3 years, and the number of R&D personnel, compared to small and medium-sized companies. Also, large-sized companies indicated a higher level of HRI, LO, HRI-LO interaction, innovation effect and business performance than did small and medium-sized companies. The results indicate that large-sized companies tend to have more innovative human resources and invest more on learning orientation than did small-sized companies, therefore, large-sized companies tend to have more success of a new product/service in the market, generating better business performance. In order to test research hypotheses, a series of multiple-regression analysis was conducted. In the regression analysis examining the impact on innovation effect, important results were generated as : 1) HRI, LO, and HRI-LO affected innovation effect, and 2) company size indicated a moderating effect. Based on the result, the impact of HRI on innovation effect would be greater in small and medium-sized companies than in large-sized companies whereas the impact of LO on innovation effect would be greater in large-sized companies than in small and medium-sized companies. In other words, innovative workforce would be more important in making new products/services that would be successful in the market for small and medium-sized companies than for large-sized companies. Otherwise, learning orientation culture would be more effective in making successful products/services for large-sized companies than for small and medium-sized companies. Based on these results, research hypotheses 1 and 2 were supported. In the analysis of a regression examining the impact on business performance, important results were generated as : 1) innovation effect, LO, and HRI-LO affected business performance, 2) HRI by itself did not have a direct effect on business performance regardless of company size, and 3) company size indicated a moderating effect. Specifically, an effect of the HRI-LO interaction on business performance was stronger in large-sized companies than in small and medium-sized companies. It means that the synergy effect of innovative human resources and learning orientation culture tends to be stronger as company is larger. Referring to these result, research hypothesis 3 was partially supported whereas hypothesis 4 was supported. Based on research results, implications for companies were generated. Regardless of company size, companies need to develop the learning orientation corporate culture as well as human resources' innovativeness together in order to achieve successful development of innovative products and services as well as to improve sales and profits. However, the effectiveness of the HRI-LO interaction would be varied by company size. Specifically, the synergy effect of HRI-LO was stronger to make a success of new products/services in small and medium-sized companies than in large-sized companies. However, the synergy effect of HRI-LO was more effective to increase business performance of large-sized companies than that of small and medium-sized companies. In the case of small and medium-sized companies, business performance was achieved more through the success of new products/services than much directly affected by HRI-LO. The most meaningful result of this study is that the effect of HRI-LO interaction on innovation effect and business performance was confirmed. It was often ignored in the previous research. Also, it was found that the innovativeness of human workforce would not directly influence in generating good business performance, however, innovative human resources would indirectly affect making good business performance by contributing to achieving the development of new products/services that would be successful in the market. These findings would provide valuable managerial implications specifically in regard to the development of corporate culture and education program of small and medium-sized as well as large-sized companies in a variety of fields.