| BackgroundPrimary lung cancer is one of the most frequent male malignant disease in the world, which is seriously threatening the health of the people. Non-small cell lung carcinoma (NSCLC) is account for 60~80% of all lung cancers. Uncontrolled cell proliferation is the hallmark of malignant tumours. Thus,the proliferative potential of tumour cells have an important value on the diagnosis, treatment and prognosis of lung cancer. Uncontrolled cell proliferation is occur in NSCLC as well as other malignant tumours, so researching on cell proliferation has become an important field. It was discovered that PCNA (Proliferating cellnuclear antigen) is a protein which is compounded by 261 amino acids . According to reports, this molecule is also known as auxiliary protein for DNA polymerase , and is associated with DNA replication and cell proliferation . Expression of PCNA increases at the end of d period, reaches its maximum in S-phase, declines during G2, M phase, and is absent in quiescent cells . It is the key point controlling the DNA duplication and cell division, so it s expression reflecting the extent of cell proliferation. Ki~67, a nonhistone protein, is a DNA-binding nuclear protein expressed at the end of d period, increases in S, G2-phase , and reaches its maximum in M-phase, declines after mitosis, and is absent in quiescent (Go) cells. It has been used to distinguish growing from non growing cells and reflecting the extent of cell proliferation. p53 suppressor gene is researched at most in the present time, it s function of biochemistry is an cell regulatory factor. p53 regulates the cell proliferation during cell life cycle and controls cells in G, -phrase turning into S-phrase, accordingly arrests the cell proliferation . It is known now that many kind of human malignant tumours have p53 gene mutation. Depletion of wild-type p53 allelomorphic gene is arise after p53 gene mutation, thus p53 losts its function of inhibiting tumor. Mutant p53 let the damaged cells continue to divide and proliferate, leading toneoplastic transformation eventuallyw. However, as the same marker correlating cell proliferation, in previous research, significance of the expression of PCNA^ Ki-67 ^ p53 proteins in NSCLC remains controversial. In addition , investigation on coexpression of PCNA> Ki~67> p53 is still rare, so the aim of this investigation is discussing the significance of the coexpression of PCNA^ Ki~67> p53 proteins in NSCLC, and providing assistance of clinical treatment and decision of prognosis.Objects and MethodsIn the study, expressions of Ki-67, PCNA and p53 were detected in a group of 135 paraffin-embedded samples from surgically resected non-small cell lung carcinomas, using immunohistochemistry(S-P methods). Control group are normal tissue at 5cm distance to mass or another lobe from the 12 patients that in the same group. Relationship between clinicopathologic characteristic and expressions of Ki-67, PCNA and p53 was analyzed. All samples are from Ningbo City Lihuili Hospital patients who were diagnosed as primary NSCLC histopathologically. All patients include Squamous cell cancer (73), adenocarcinoma (57) and other NSCLC (5). 106 males and 29 females, aged 38 to 81yrs, the mean age was 59.9 yrs. All tumorswere staged according to the International Union Against Cancer TNM stage system (2002) after the surgery : I stage 42, II stage 36, Ilia stage 48, above Illb stage 9. All tumor samples were paraffin-embedded . Tumor sections were cut by 4um, and deparaffinaged to hydration. In the study, expressions of Ki-67, PCNA and p53 were estimated using immunohistochemistry (S-P methods). Phosphate buffered saline were used with first antibodies as negative control, whereas lung cancer samples were used as a positive control. The percentage of immunopositive cells in representative areas of the sections was assessed by two pathologists. The percentages of immunopositive cells of PCNA> Ki~67> p53 were used as the labeling index respectively. Standard of discrimination (Dworakowska D) was used as criteria. A percentage of immunopositive cells of PCNA^ Ki~67> p53 above 10% were scored as "positive" , and under 10% as "negative" .The two groups were analyzed by Chi-square test with SPSS 11.5 for windows. P<0.05 was regarded as statistical significance.ResultsThere were higher expressions of PCNA, Ki-67, p53 in tumor, which demonstrated significant difference with theexpression of PCNA, Ki-67, p53 in controlled lung tissue. Thehighest positive ratio in NSCLC tumour cells was PCNA,then wasKi-67, and p53 was the lowest one. all the three were higher insquamous cell carcinoma than those in adenocarcinoma. Expressionof PCNA is 80.2% positive in squamous cell carcinoma and 77.2% positive in adenocarcinoma. When it is grouped by tumourdiameter of 5cm , the larger one has higher positive expressionof PCNA which showing statistical difference (p<0.05) . Theexpression of PCNA in tumor with lymphonodes involvement ishigher than that with no lymphonodes involvement, but showing nostatistical difference. In this study,it is also grouped by age(^50, 50~70, =70yrs),the result shows that the expression ofPCNA in = 50yrs group is higher than in the elder, whichdemonstrating the activity of proliferation is higer in = 50yrsthan in the elder , but showing no statistical difference. Theexpression of PCNA demonstrate no statistical difference ingroupes divided by histologic type, differentiated degree,postoperative -pathological stages(pTNM). Expression of Ki-67is 61. 4% in squamous cell carcinoma and 50. 9% in adenocarcinomademonstrating no statistical difference in groupes divided by age,histologic type,differentiated degree , tumor size, lymphonodeinvolvement , postoperative-pathological stages ( p>0.05 ) .Expression of p53 is 60. 3% in squamous cell carcinoma and 40. 4 % in adenocarcinoma, and is higher in =50yrs group than that in the elder, but showing no statistical difference. In addition, Expression of p53 is 60. 3% in squamous cell carcinoma, which is higher than others, demonstrating no statistical difference. It also demonstrates no statistical difference in groupes divided by histologic type, differentiated degree, tumor size, lympho nodes involvement, postoperative - pathological stages. The expressions of PCNA, Ki~67, p53 in tumor are related with each other in some degree.Conclusions1 There were higher expressions of PCNA, Ki-67, p53 in NSCLC compared with controlled lung tissue, which demonstrated significant statistical difference.2 Larger tumor than 5cm has higher expression of PCNA, which demonstrated higher proliferation ability of NSCLC in larger tumor.3 Expression of PCNA> Ki-67> p53 in squamous cell carcinoma is higher than in adenocarcinoma, indicated that proliferation ability of squamous cell carcinoma is higher than in adenocarcinoma.4 Expression of PCNA is higher than Ki~67 , p53 in detecting the activity of proliferation. The expressions of PCNA, Ki~67, p53 in NSCLC are related with each other in some degree. |
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