Journal of Pathology and Translational Medicine

Original Articles

p27Kip1 Expression and Apoptotic Index in Prostatic Adenocarcinoma.: Eun Sook Nam, Duck Hwan Kim, Hyung Sik Shin, Young Euy Park, Dae Yul Yang; Korean J Pathol. 1999;33(12):1139-1145.

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Abstract PDF: p27kip1, a cyclin dependent kinase inhibitor, has been recognized as a negative regulator of cell cycle. To investigate the role of p27kip1 on progression of cancer and apoptotic pathway, we analyzed p27kip1 expression using immunohistochemical stain in 40 cases of prostatic adenocarcinoma and apoptotic index by TUNEL method in 30 cases of prostatic adenocarinoma. Both were correlated with Gleason grade and Gleason score. Loss of p27kip1 expression was more frequent in prostatic adenocarcinomas of higher score (Gleason score 7 to 10) (60.7%) than in those of lower score (Gleason score 4 to 6) (33.3%) (p<0.05). The value of mean apoptotic index of carcinoma was 1.13+/-0.26, 1.80+/-0.91, 2.06+/-0.79, and 2.12+/-0.82 in grade 2, 3, 4, and 5, respectively, and was positively correlated with grade of carcinoma (p<0.05). Mean apoptotic index of higher Gleason score (score 7 to 10; 2.05+/-0.63) was also significantly increased than in lower Gleason score (score 4 to 6; 1.34+/-0.39) (p<0.05). Mean apoptotic index in cases with and without p27kip1 expression was 1.92+/-0.86 and 1.89+/-0.81, respectively (p>0.05). These results suggest that loss of p27kip1 expression and increased apoptotic index may be the morphologic markers to predict the behavior of prostatic adenocaricnoma. The role of p27kip1 on apoptotic pathway seems to be meager in this study and needs further study.

Expression of p27Kip1 Protein in Colorectal Adenocarcinoma.: Hyang Im Lee, Duck Hwan Kim, Eun Sook Nam, Hye Rim Park, Seoung Wan Chae, Chul Jae Park, Jeong Rye Kim, Hyung Sik Shin; Korean J Pathol. 2000;34(2):132-137.

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Abstract PDF: p27Kip1 has been recognized as a negative regulator of cell cycle. Reduced level of p27 expression is associated with development and aggressiveness of several human tumors. To investigate the role of p27Kip1 on progression of colorectal adenocarcinoma, we studied 40 cases of human colorectal adenocarcinomas for expression of p27Kip1 protein using an immunohistochemical method, and compared these results with known prognostic parameters of colorectal adenocarcinoma. Among 40 cases of colorectal adenocarcinomas, p27Kip1 expression was detected in the nuclei of tumor cells in 14 cases (35%). The expression rate of p27Kip1 protein was significantly lower in the cases with lymph node metastasis (25.8%) than in those without lymph node metastasis (66.6%) (p<0.05). But it did not correlate with other parameters such as tumor size, histologic grade, vascular invasion, and Ki-67 labeling index. The results suggest that reduced expression of p27Kip1 protein plays a role in biologically aggressive behavior of colorectal adenocarcinoma.

Expression of p27Kip1 Protein in Carcinoma of the Urinary Bladder.: Ki Kwon Kim, Jung Ran Kim; Korean J Pathol. 2000;34(5):341-348.

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Abstract PDF: The cyclin-dependent kinase (cdk) inhibitor p27Kip1 gene is a powerful molecular determinant of cell cycle progression. Loss of expression of p27Kip1 has recently been shown to be predictive of disease progression in several human malignancies. The prognostic value and expression of p27Kip1 have been incompletely studied in bladder cancer. In this study, we investigated the relationship between p27Kip1 protein expression and clinicopathologic parameters in 50 cases of carcinoma of the urinary bladder by conducting immunohistochemical analysis and DNA flow-cytometry. Malignant bladder tissue demonstrated a heterogeneous pattern of p27Kip1 immunoreactivity. In addition, there was progressive loss of expression with increasing tumor grade. The expression of p27Kip1 protein was unrelated to stage, DNA ploidy and S phase fraction (SPF). SPF was unrelated with tumor grade and DNA ploidy. The results indicate that p27Kip1 is frequently expressed in well differentiated transitional cell carcinomas of the urinary bladder but less often expressed in muscle-invasive transitional cell carcinomas. The expression of p27Kip1 and its prevalence in low-grade tumors may reflect growth regulatory influences and potential inhibiting action in tumor progression and novel predictive markers of the biological potential of bladder tumors.

Analysis of Expression of p63 in Cervical Neoplasia Comparing with Other Immunohistochemical Markers .: Min Yeong Kim, Sam Hyun Cho, Moon Hyang Park; Korean J Pathol. 2003;37(5):333-341.

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Abstract PDF: BACKGROUND
The reproducibility in grading a cervical intraepithelial neoplasia (CIN) are not perfect. The aim of this study was to assess the value of the immunohistochemical expression of p63 and the other biomarkers for grading a CIN (dysplasia and in situ carcinoma), and diagnosing invasive carcinomas.
METHODS
Sixty six cervical specimens were immunostained with the monoclonal antibodies against p63, Ki-67, p27Kip1, and p53 to determine the localization.
RESULTS
The p63 positive cells are well linked with squamous cell maturation and the degree of dysplasia. In mild dysplasia, the p63 positive cells were localized to the basal and parabasal cells, which gradually extended into the middle and upper layers in moderate and severe dysplasia. p63 expression was strong in immature squamous epithelium and invasive squamous cells, but was constantly absent in an adenocarcinoma. The Ki-67 positive cells were scattered from the parabasal cells to the superficial cells in accordance with the degree of dysplasia. p27Kip1 expression was noted in the intermediate cells in the normal cervix. In CIN, the p27Kip1 positive nuclei tended to extend to the basal cells, but it showed no diagnostic consistency in an invasive carcinoma. p53 expression was also variable.
CONCLUSION
p63 is a useful diagnostic adjunct for grading CIN as well as for detecting microinvasion and squamous differentiation in invasive carcinoma. However, immunohistochemical expressions for the p27Kip1 and p53 have no correlation with the grade of CIN and squamous cell carcinoma.

Immunohistochemical Study of p27Kip1 Expression in Gastric Adenomas and Early Gastric Carcinomas: Analysis of 65 Cases.: Na Hye Myong; Korean J Pathol. 2003;37(5):325-332.

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Abstract PDF: BACKGROUND
Recent studies have suggested that loss of p27Kip1 expression correlates with poor prognosis in gastric carcinomas, although the published data is still controversial. However, there are very few reports on the immunohistochemical expression of p27Kip1 in gastric adenomas and its significance in the progression of gastric adenomas to early gastric carcinomas (EGCs) is unclear. We therefore performed an immunohistochemical study for p27Kip1 expression in gastric adenomas with low- and high-grade dysplasia and EGCs to investigate the role of p27Kip1 expression in gastric carcinogenesis.
METHODS
We collected 45 cases of endoscopic mucosal resection specimens which were diagnosed as gastric adenomas and 20 cases of gastrectomy specimens showing EGCs. Using a monoclonal antibody against p27Kip1, the im- munohistochemistry was performed on paraffin-embedded specimens.
RESULTS
The loss of p27Kip1 immunoreactivity (<5% of the tumor cells) tended to be observed more frequently in high-grade adenomas than in the low-grade. The loss was found significantly higher in the EGCs than in both high-grade and low-grade adenomas (p=0.000). Gastric adenomas with villous component showed significant loss of p27Kip1 expression (p=0.057).
CONCLUSION
These results suggest that loss of p27Kip1 expression can play a role in the progression of gastric adenomas into adenocarcinomas and the villous component allows reliable estimation of the possibility for malignant transformation.

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