Clinical Significance Of Expression Of P14ARF And P16 Protein In Cervical Carcinoma And Intraepithelial Neoplasia

Objective: To study the expression of tumor suppressor----p14ARF andp16 protein in cervical cancer and intraepithelial neoplasia and clinical significance.Methods: 46 patients with SCC, 18 patients with mild CIN , 35 patients with moderate or severe CIN and 8 patients with hysteromyoma who received cervical biopsy , conization or hysterectomy between January 2000 and June 2005 in the department of Gynecology and Obsterics of Shandong provincial Qian FO Shan Hospital were reviewed for study. The median age of patients with SCC was 50 years (ranged from 26 to 70) . The median age of CIN patients was 39.6 years (ranged from 21 to 67). The median age of normal cervical group was 45. 5(ranged from 42 to 66). All the patients underwent radiotherapy or chemotherapy before surgery. Modified FIGO system was used for both grading and staging. The expression of p14ARF and p16 monoclonal antibody were detected by S-P immunohistochemistry . The expression degree of the antibodies were measured by Image-Pro Plus 5. 0 image analysis software. 5 representative random field of vision were selected in every tissue slice , then we calculate the IOD of every field of vison and the average number acted as the slice coloring degree. The result was demonstrate by x±s. Student- Newman- Keuls variance analysis, t test and regression analysis were used to investigate.Results: 1. The p14ARF positive cells showed well-distributed brown color or some brown coarse grains confined to cell nuclei. Normal cervical epithelium tissue and CIN1 lesions were negative for p14ARF, except one case of CIN1 lesions assumed faint p14ARF-stained cells scattered near basal layer. The expressions of p14ARF were both positive in CIN2/3 lesions and SCC lesions, and the expression of the two proteins in SCC is significant stronger than that in CIN2/3 (P<0. 05) . The CIN2/3 lesions showed focal p14ARF staining near basal layer and in metastatic cells. In early SCC, the positive expression of p14ARF mainly distributed in those punctiform breakthrough cells. In advanced SCC lesions, tumor cells showed diffuse dyed.2. The p14ARF positive cells showed well-distributed brown color or some brown coarse grains confined to cytoplasm or both cytoplasm and cell nuclei. Normal cervical epithelium tissue and CIN1 lesions were negative for p16. Overexpression of p16 mainly observed in superficial cell layer in CIN2/3 lesions which was different from that of p14ARF and might be caused by the functions and distribution of it. P16 showed diffusely distributed in SCC lesions. The expression in SCC were markedly stronger than that in CIN.3. The p14ARF IOD of 46 SCCs were as follws: the IOD of the poorly differenciated was 379071.1 ± 123.45, the highly and morderately differentiated' s was 379071.1 ± 123. 45; the 36 cases of non-lymphoid metastasis 159689.3 ± 563.9, 10 cases of positive lymph node 412560.85 + 267. 11; 33 cases of FIGO stage I tissue 241800. 1±212. 30 and stage IK III 185370. 0+744. 62. By regression analysis the expression of p14ARF was considerately correlated with histopathologic grade and lymphoid metastasis (P<0. 01) but had none crrelation with FIGO stages (P>0. 01) . Marked immunochemistry for p14ARF was observed in poorly differentiated cancers and in cancers with lymph node metastasis.4. The IOD of 46 SCCs were as follws: the IOD of the poorly differenciated was 270516.4± 148, the highly and morderately differentiated' s was 266825. 1 ± 195. 58; the 36 cases of non-lymphoid metastasis 284657.6 ± 312.20, 10 cases of positive lymph node 300505.74 ±421. 56; 33 cases of FIGO stage I tissue 367150. 1±227. 75 and stage II , III 108508. 8±111. 39. By regression analysis the expression of p16 was considerately correlated with FIGO stages (P<0.01) but had none crrelation with histopathologic grade and lymphoid metastasis (P>0.01) . Marked immunochemistry for p16 was observed in stage I cancers.5. The relationship between the expression of p14ARF and that of p16 was linearity positive correlation (r = 0. 663, P<0. 01) , but no consideratly significant deviation was showed between them (P>0. 05).Conclusion: Overexpression of p14ARF suggested that the cells had initiated malignant change, and had gained invasive and metastatic abilities. Therefore, p14ARF may be a better cervical tumor marker.