Objective To study the expression of p16 and Rb gene in primary gallbladder carcinoma (PGC). MethodsFiftysix cases of PGC and 26 of gallbladder benign lesions were observed by immunohistochemistry (SP). ResultsThe positive rates of p16 and Rb protein in PGC were 46.3% and 71.4% respectively. No association of Rb expression with histological grade, histological type, invasion, metastasis and prognosis was found. There were close correlation between p16 expression and invasion, metastasis as well as prognosis. The inverse correlation of p16 and Rb gene expression in PGC was confirmed. Conclusion The loss of p16 or Rb gene protein is an important molecular event in PGC,and closely related to the block in the negative regulatory pathway of all cell cycle. The detection of p16 protein may be useful in evaluating biological characteristics and prognosis in PGC.
ObjectiveTo determine the frequency and type of p16 gene homozygous deletion and mutation with the progression of human gastric carcinogenesis.MethodsPCR （polymerase chain reaction），SSCP (single strand conformation polymorphism) and DNA sequencing were performed on 50 operative tissues, which included 7 early gastric cancer and 43 advanced gastric cancer. In this group there were 36 male and 14 female patients aged 35 to 68,which included 30 welldifferetiated adenocarcinoma and 20 poordifferentiated carcinoma; 19 patients with lymph node metastases.ResultsTotal mutation frequency of p16 gene was 8.00%(4/50), including 14.29%(1/7) of early cancer and 7.00%(3/43) of advanced cancer，there was no significant difference between early and advanced cancer （P＞0.05）. In addition, p16 gene mutation was not related to site，location，grade of tumor differentiation and lymph node metastases, respectively. Total deletion frequency of p16 gene was 16.00%(8/50), of which 18.60%(8/43) was detected in advanced cancer, but no cases in early cancers. There was a significant difference between early and advanced cancer （P＜0.05）, and frequency p16 gene homozygous deletion was related to grade of tumor differentiation and lymph node metastases, respectively. Direct DNA sequencing displayed that 4 point mutations detected in 99,125,433,441 base, there were 3 missense mutation and 1 samesense mutation, no deletion or insertion was found. Conclusionp16 gene mutation is an early event in gastric carcinogenesis，it helps early diagnosis of human gastric carcinoma. p16 gene homozygous deletion is a late event in gastric carcinogenesis，it might relate to metastases and recurrence of gastric cancer.
Objective To study the association and the effect of the expression of p16 and p53 protein on the occurence and development of gallbladder carcinoma. Methods The expression of p16 and p53 protein were detected in 40 cases of gallbladder carcinoma with immunohistochemical method. Results The expressions of p16 and p53 protein were closely correlated to the tumor pathological grade, lymph mode metastasis and prognosis. p16 protein was correlated to the Nevin classifications. Conclusion The results indicate that the low expression rate of p16 protein occurred in the advanced stage of gallbladder carcinoma. The expression of p16 and p53 protein are helpful in judging the malignant degree and prognosis of primary gallbladder cancer.
Objective To investigate expression of p16 protein in breast cancer and its clinical significance. Methods Using immunohistochemical techniques (LSAB) the expression of p16 protein in 107 breast carcinomas was examined. Results The positive rate of p16 protein expression was 40.19% (43/107). The p16 protein over expression of the cases surviving ≤5 years and surviving ≥10 years were 8.00% and 75.68% respectively. Conclusion Expression of p16 protein might play an important role in the prognosis of breast cancer.
Objective To observe the action and correlation of p16 and estrogen receptor (ER) in papillary thyroid cancer (PTC).Methods Using immunohistochemical method, the p16 and ER in 50 cases of PTC were detected. Results The expression of p16 and ER was associated with the cellular differentiation, the lymphatic metastasis and prognosis in PTC. Conclusion It is helpful to detect the p16 protein and ER for analyzing the cellular differentiation degree and prognosis in PTC.
Objective To study the expression and its clinical significance of p16 in human gastric carcinomas. MethodsThe expression of p16 protein and mRNA in human gastric carcinomas using SP immunohistochemical and in situ hybridization (ISH) methods were examined. Results Of the 85 cases tested, 65.88% (56 cases) showed positive staining of p16 protein in the primary lesions. The positive rate of p16 protein was significantly lower in the cases with deep invasion, poor differentiation or shorter survival periods (Ｐ＜0.05). The positive rate of p16 mRNA expression in human gastric carcinomas was 47.37% (in 38 cases). Conclusion p16 gene may correlate with the development and progress of gastric carcinomas. The expression of p16 gene may be a useful tool for showing biological behavior and prognosis of human gastric carcinomas.
ObjectiveTo investigate the expression of p16INK4a in nucleus pulposus (NP) and to clarify its relationship with intervertebral disc degeneration so as to provide evidence for biological repair of intervertebral disc. MethodsThe NP specimens were obtained from 17 patients with intervertebral disc degeneration undergoing discectomy, who aged 40-50 years (mean, 45.4 years). Based on the preoperative MRI, there were 10 cases of grade Ⅲ degeneration, and 7 cases of grade IV degeneration. Cell senescence was evaluated by detecting senescence-associated β-galactosidase (SA-β-gal) activity. Senescence marker (p16INK4a) and disc degeneration markers [A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS 5), Aggrecan, and Sryrelated HMG box transcri ption factor 9 (Sox-9)] were determined in the NP specimens with immunohistochemistry and Western blot. The correlation between ADAMTS 5 and p16INK4a was analyzed. ResultsClustered distribution of green SA-β-gal-positive cells was seen in the NP with grade Ⅲ and IV degeneration. A few single round SA-β-gal-positive NP cells (NPCs) wrapped by the layered extracellular matrix were also seen in the NP with grade Ⅲ degeneration. It was difficult to see single distribution of NPCs in the NP with grade IV degeneration. The percentage of SA-β-gal-positive cells was 22.7%±5.4% and 37.1%±7.6% in the NP with grade Ⅲ and IV degeneration respectively, showing significant difference (t=-9.666, P=0.000). The percentages of p16INK4a-positive and ADAMTS 5-positive NPCs in the NP with grade IV degeneration were significantly higher than those with grade Ⅲ degeneration (P<0.05). The percentages of Aggrecan-positive and Sox-9-positive NPCs in the NP with grade IV degeneration were significantly lower than those in the NP with grade Ⅲ degeneration (P<0.05). The protein expressions of Aggrecan and Sox-9 in the NP with grade IV degeneration were significantly lower than those in the NP with grade Ⅲ degeneration (P<0.05). The NP with grade IV degeneration showed significantly higher protein expressions of p16INK4a and ADAMTS 5 (P<0.05). Importantly, there was a good correlation between p16INK4a and ADAMTS 5 protein expressions (r=0.908, P=0.000). ConclusionPremature senescent NPCs increase in the NP with the advancing disc degeneration. The expression of p16INK4a and its association with degeneration grades suggest that the p16INK4a may play a significant role in the pathogenesis of intervertebral disc degeneration.
【Abstract】Objective To demonstrate the role of p16 protein and Rb protein in the formation and progression and their relationship in thyroid carcinoma. Methods p16 and Rb from 46 patients with thyroid cancer were detected by SP immunohistochemistry. Results In thyroid carcinoma,the p16 positive rate was decreased with the decline of differentiation. There was an inverse correlation between the rates of p16 positive expression and involvement of lymph node,clinical stage and prognosis index.The Rb protein was not present in any cases as a nucleus staining. Conclusion The p16 gene is likely to play an important role in the genesis and malignant progression of thyroid carcinoma,while the Rb gene is not .
The expression of bcl-2 and p16 in 25 cases of gallbladder mucosa hyperplasia, 40 cases of gallbladder carcinoma and 25 adjacent normal gallbladder mucosa tissue was detected with immunohistochemical staining. Normal gallbladder mucosa was uniformly negative. Bcl-2 and p16 positive rate were significantly higher in hyperplasia and carcinoma than in normal tissue (Ｐ＜0.01). Expression of bcl-2 and p16 got higher with the increasing degree of hyperplasia, p16 was associated with lymph node metastasis and depth of invasion of carcinoma of the gallbladder. The results suggest that bcl-2 and p16 expression play an important role in tumorigenesis, p16 can be used as a prognostic index for gallbladder carcinoma.