| Today it is realized that the carcinogenesis and development of lung cancer is a complicated process referring to multiple-phased, multigenic control disorder and many molecular abnormalities, including activiting of oncogene, disactiviting of tumor suppressor gene, which lead to uncontrolled cell proliferation and malignant transformation. With the advance in molecular biology and hereditary science, people pay more attention to the role of cell cycle disruption in the carcinognesis and development of lung cancer. The P16-cyclin Dl-Rb pathway plays important role in Gl phase regulation. P16 functional defects, Cyclin Dl overexpression or Rb alteration will disrupt the balance of cell cycle regulation and promote carcinogenesis. Up to now, some studies have reported the alteration of PI6, Cycin Dl and Rb in non-small cell lung cancer (NSCLC) respectively, but the results are inconsistent. PCNA, proliferative cell nuclear antigen, is the necessory component for DNA duplication of cell chromatosome, its synthesis and expression being related to cell proliferative cycle. PCNA proliferative index (PI) is one kind of simple, feasible method for evaluating proliferative activity in tumor cells. Combined detection of p16, cycin Dl and Rb in NSCLC has been done a little. There are few reports about probing into their relationship with cell proliferative activity.Applying immunohistochemical SABC or SP techniques, we studied expression of P16, Cyclin Dl and Rb proteins and their relationship with cell proliferativeactivity, exploring their reciprocal effects among them and their correlation with carcinogenesis, development and biological behavior in NSCLC. All these will provide people new thoughts and basis to diagnose and cure cancer.Materials and Methods: 88 NSCLC resected specimens (archival paraffin blocks 1994-1999) were collected from the first and second clinical medical college, Zhengzhou University, and all the specimens were formallin-fixed and paraffin-embedded. The patients, range 33-72 years, average 57.1, 60 males and 28 females, 63 squamous cell carcinoma and 25 adenocarcinoma, had not received chemo- or radiation therapy. According to UICC TNM system (1997), 48 were in stage I - II, 40 were in stage III-IV. 20 normal lung tissue specimens were collected as a control group. Immunohistochemical SABC or SP techniques were used to detect the expression of P16, Cyclin Dl, Rb and PCNA. PCNA immunstain-positive cells were enumerated as proliferative index under the microscope 400 among approximately 1000 counted rumor cells. With SPSS 10.0 software package, Chi-Square test, t test and correlation test were used to analyze the data. P<0.05 was considered statistically significant.Results: 1. P16 expression loss rate was 51.1% (45/88). There was no significant difference according to histological types (squamous cell carcinoma or adenocarcinoma), differentiation (well or moderate, poor), lymph node metastasis (positive or negative) and stage( I - II or III-IV) (P>0.05). 2. Cyclin Dl expression rate was 52.3% (46/88). There was no significant difference according to histological types and stages (P>0.05), but there was significant difference according to differentiation and lymph node metastasis (P<0.05). Cyclin Dl expression was significantly higher in patients with poor cell differentiation and with lymph node metastasis. 3. Rb expression loss rate was 21.6% (19/88), and there was no significant differece according to histological types, differentiation, lymph node metastasis and stages (P>0.05). 4. There was inverse correlation between expression of Rb and P16, a direct correlation between expression of Rb and Cyclin Dl, no correlation between expression of P16 and Cyclin Dl. 5. PCNA proliferative index showed significantdifference according to Cyclin Dl or Rb status, PI 45.5 + 15.6, 27.0+21.6, 30.8 + 17.1, 58.1 +19.2, for Cyclin Dl(+), Cyclin Dl(-), Rb(+), Rb(-) respectively (P<0.01). Cyclin Dl expression or Rb expression loss was associated with higher cell proliferative activity. |
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