Prognostic Significance Of P27 Kip1 Expression Research Articles

P27Kip1 expression and its prognostic implication in breast carcinoma: a meta-analysis

To evaluate the relationship between p27Kip1 low expression in breast cancer and its prognostic implication in breast carcinoma patients. Methods All data that were associated with the study of the relationship between p27Kip1 and the prognosis for breast cancer was pooled from Cochrane library, PubMed, Embase and Medlinebase. The outcome was measured using the risk ratio (RR). Data pooling was performed by RevMan 4. 2. Results 6457 patients from 20 studies were included in this meta-analysis. RR estimate of overall survival (OS) for patients with low level p27Kip1 was 2.07 [1.66,2.60] (P<0.01). For disease free survival (DFS), the pooled RR was 1.27 [1.10,1.47] (P<0.05). The combined RR estimate of relapse free survival (RFS) for patients with low level of p27Kip1 was 1.49 [0.92, 2.42] (P >0.05). In patients with lymph node negative breast carcinoma, the combined RR for OS and RFS were 1.98 [1.34,2.91] (P <0.01) and 1.28 [0.45,3.65] (P > 0.05), respectively. Among the patients with lymph node positive breast carcinoma, the combined RR for OS and RFS was 1.92 [1.31, 2.82] (P=0.0009) and 1.35 [0.96,1.89] (P>0.05) respectively. Conclusions Low level of p27Kip1 appears to be an independent prognostic factor to OS and DFS of breast cancer patients but not to RFS. Additional studies with large patient number and widely accepted practical methods are required to derive the precise prognostic significance of p27Kip1 expression in breast cancer patients.

Prognostic Significance of p27kip1 Expression in Node Negative Colorectal Carcinoma

Purpose: Dukes’ A & B colorectal cancer patients are often excluded from adjuvant chemotherapy following potentially curative surgery because they are expected to have good long-term survival. However, actually 20～30% of these patients suffer from recurrent disease, so it would be helpful for these patients of recurrent disease to be able to select a high risk group. Methods: In 78 Dukes’ A & B colorectal cancers, we investigated by immunohistochemistry the role of molecular markers, such as p27kip1, p53, Ki-67, and Skp2, in identifying high-risk patients. Results: Patients with low p27kip1 expression showed poor overall survival compared to those with high p27kip1 expressions (55.3 versus 66.7 months, P=0.018). The only significant factor associated with p27kip1 expression was p53 expression. The low p27kip1 expression and positive p53 expression group had poor overall survival (54.3 months, P=0.036). Conclusions: In a node-negative colorectal carcinoma, the molecular marker p27kip1 does not play an independent prognostic role, but it may have prognostic significance in correlation with other markers such as p53, Ki-67, and Skp2. The assessment of molecular alterations may be useful to node-negative colorectal patients in identifying the high risk group that may benefit from adjuvant chemotherapy.

Prognostic significance of p27(kip-1) expression in colorectal adenocarcinomas is associated with tumor stage.

Although the decreased expression of p27(kip-1), a cyclin-dependent kinase inhibitor, has been correlated with advanced tumor stage and short survival of patients with colorectal adenocarcinomas (CRCs), its prognostic value based on the tumor site, tumor stage, and patient ethnicity was not assessed. Therefore, in this study, we investigated whether the prognostic value of p27(kip-1) expression varies with the tumor site, tumor stage and patient ethnicity. We evaluated 206 (85 African Americans and 121 Caucasians) archival tissue specimens of first primary CRCs for immunohistochemical expression of p27(kip-1), and its prognostic significance was analyzed using univariate Kaplan-Meier and multivariate Cox regression survival methods. Although, similar proportion of CRCs with decreased p27(kip-1) expression was observed in all stages (range, 26-36%), the decreased p27(kip-1) expression has been shown as a marker of poor prognosis only for patients with stage III tumors both in univariate (log-rank test, P = 0.014) and multivariate (hazard ratio = 3.2, 95% confidence interval = 1.3-7.7; P = 0.01) survival analyses. The decreased expression of p27(kip-1) was associated with a high histologic grade (P = 0.016) in stage II CRCs, and with distal tumors (P = 0.001), tumor invasion (P = 0.044), and with local recurrence (P = 0.008) in stage III CRCs. No prognostic significance was found for p27(kip-1) expression in stages I, II, or IV CRCs, and its prognostic value was not associated with either ethnicity or tumor location. These studies suggest that decreased expression of p27(kip-1) is an indicator of poor prognosis and aids in identifying a subset of patients with aggressive forms of stage III CRCs.

Expression of p27KIP1 in human gliomas: Relationship between tumor grade, proliferation index, and patient survival

Numerous studies examining the prognostic significance of p27KIP1 expression in human cancer have shown that decreased expression often is an independent prognostic factor associated with worse survival. However, the prognostic value of p27KIP1 expression in gliomas is less well established. To further address this issue, we evaluated the relationship between p27KIP1 protein expression in a series of 50 astrocytomas with clinicopathologic parameters including age, tumor grade, MIB-1 proliferation index, and patient survival using both Western blot analysis and immunohistochemistry. The level of p27KIP1 protein expression in 9 nonneoplastic brain tissue specimens served as a control. Sixteen high-grade astrocytomas were analyzed by Western blot, and 26 high-grade astrocytomas were analyzed by immunohistochemistry for levels of p27KIP1 protein expression. Regardless of the technique used to measure p27KIP1, approximately 50% of the high-grade tumors were low expressors and the other 50% were high expressors. Thus, expression of p27KIP1 was independent of tumor grade. Loss of p27KIP1 expression is often associated with an increase in proliferative activity. We measured the rate of tumor cell proliferation using MIB-1 immunostaining in 16 high-grade astrocytomas to determine whether there was an inverse correlation between p27KIP1 expression and proliferation. No correlation between p27KIP1 expression and MIB-1 labeling index or patient survival was found. Using immunohistochemistry, we noted that the staining pattern of p27KIP1 in glioblastomas was mainly in the pseudopalisading cells that outline areas of necrosis. Because p27KIP1 can be up-regulated by hypoxia, this staining pattern would be consistent with our observation that hypoxia-inducible factor 1α is expressed primarily in pseudopalisading tumor cells around necrotic zones. It has been shown that a high level of p27KIP1 prevents apoptosis in hypoxic cells. Thus, maintenance of high levels of p27KIP1 in gliomas could result from the hypoxic microenvironment present within the tumor. No correlation was found between p27KIP1 expression and any of the clinicopatholgic parameters tested, including patient age and tumor grade, the 2 strongest predictors of survival among glioma patients. HUM PATHOL 34:48-53. Copyright 2003, Elsevier Science (USA). All rights reserved.

Prognostic significance of p27KIP1 expression in resected non-small cell lung cancers: analysis in combination with expressions of p16INK4A, pRB, and p53.

Whether a prognostic role for expression of the tumor suppressor gene (TSG) products exists in resected non-small call lung cancers (NSCLCs) remains controversial. Our study was performed to determine the value of TSGs expressions for patients survival in NSCLCs. We examined 108 resected NSCLCs for the expression of TSG products, p27(KIP1), p16(INK4A), pRB, and p53 that govern cell cycle transition by immunohistochemistry and compared them with patient clinical characteristics and prognoses. Abnormal expressions of p27(KIP1), p16(INK4A), pRB, and p53 were found in 61 (57%), 53 (49%), 42 (39%), and 48 (44%), respectively, of the 108 NSCLCs. Univariate analysis showed abnormal expression of p27(KIP1) to be a strong indicator for poor patient survival, not only in the total cohort (P = 0.0024), but also in subgroups with T1-T2 (P = 0.016), N0 (P = 0.047), and squamous cell carcinomas (P = 0.026), but not according to the expression of p16(INK4A), pRB, or p53. In the Cox regression analysis, p27(KIP1) expression was found to be an independent prognostic factor (P = 0.0148) and associated with pathological stage (P = 0.0278). Our results suggest that abnormal p27(KIP1) expression may be a useful indicator to predict postoperative prognosis, especially in patients with early stage NSCLCs, as compared to other TSG products examined.

Low expression of p27Kip1, a cyclin‐dependent kinase inhibitor, is a marker of poor prognosis in synovial sarcoma

BACKGROUND Low expression of p27kip1, a dominant cyclin-dependent kinase inhibitor involved in G1-S transition of the cell cycle, recently has been reported to be associated with aggressive tumor growth. It has been shown that active cell proliferation alludes to poor prognosis in patients with synovial sarcoma. However, to the authors' knowledge, little is known about the clinicopathologic significance of p27kip1 in synovial sarcoma. METHODS p27kip1 expression was examined immunohistochemically in 55 cases of primary synovial sarcoma, and the relations between p27kip1 expression and several cell proliferation markers, i.e., mitotic index (MI), Ki-67 labeling index (Ki-67 LI), and clinicopathologic parameters related to poor prognosis, were determined. Univariate and multivariate survival analyses were performed to evaluate the prognostic significance of p27kip1 expression in synovial sarcomas. RESULTS p27kip1 labeling index (p27kip1 LI) correlated inversely with MI (r = −0.44, P = 0.0007) and Ki-67 LI (r = −0.63, P < 0.0001). Of the clinicopathologic parameters examined, tumor necrosis (P = 0.019) and American Joint Committee on Cancer (AJCC) stage (P = 0.021) correlated significantly with p27kip1 LI. Survival analysis showed that p27kip1 LI was an independent prognostic factor for overall survival in patients with synovial sarcoma (P = 0.0031). CONCLUSIONS The study results suggested that low expression of p27kip1 may be useful as a marker of poor-prognosis synovial sarcoma. Cancer 2001;91:1005–12. © 2001 American Cancer Society.

Low expression of p27Kip1, a cyclin-dependent kinase inhibitor, is a marker of poor prognosis in synovial sarcoma

Low expression of p27(kip1), a dominant cyclin-dependent kinase inhibitor involved in G1-S transition of the cell cycle, recently has been reported to be associated with aggressive tumor growth. It has been shown that active cell proliferation alludes to poor prognosis in patients with synovial sarcoma. However, to the authors' knowledge, little is known about the clinicopathologic significance of p27(kip1) in synovial sarcoma. p27(kip1) expression was examined immunohistochemically in 55 cases of primary synovial sarcoma, and the relations between p27(kip1) expression and several cell proliferation markers, i.e., mitotic index (MI), Ki-67 labeling index (Ki-67 LI), and clinicopathologic parameters related to poor prognosis, were determined. Univariate and multivariate survival analyses were performed to evaluate the prognostic significance of p27(kip1) expression in synovial sarcomas. p27(kip1) labeling index (p27(kip1) LI) correlated inversely with MI (r = -0.44, P = 0.0007) and Ki-67 LI (r = -0.63, P < 0.0001). Of the clinicopathologic parameters examined, tumor necrosis (P = 0.019) and American Joint Committee on Cancer (AJCC) stage (P = 0.021) correlated significantly with p27(kip1) LI. Survival analysis showed that p27(kip1) LI was an independent prognostic factor for overall survival in patients with synovial sarcoma (P = 0.0031). The study results suggested that low expression of p27(kip1) may be useful as a marker of poor-prognosis synovial sarcoma.

Prognostic significance of p27(Kip1) expression in colorectal cancer: a clinico-pathological characterization.

This study has evaluated the expression of the cyclin-dependent kinase inhibitor p27(Kip1) in 89 colorectal cancers (CRCs) using immunohistochemistry and has related p27 levels to clinico-pathological characteristics, tumour cell proliferation, and the expression of other G1-S transition regulatory proteins. Low levels of p27 were common in CRCs; 11 per cent of the tumours expressed very low levels and 44 per cent had p27 labelling indices (LIs) below 50 per cent. Except for depth of tumour invasion, no significant correlation was found between p27 expression and Dukes' stage, differentiation, growth pattern, tumour type or lymphocytic infiltration. Interestingly, tumours expressing low or very low p27 LIs were predominantly found in the right colon (p=0.026). Expression of p27 was a strong predictor of survival, both in univariate and in multivariate survival analyses; patients with tumours of p27 LI less than 50 per cent had an impaired prognosis (p=0.0069). p27 expression did not correlate with tumour cell proliferation, or with expression of cyclin D1 or the retinoblastoma protein (pRb). These findings support the view that p27 not merely controls cell cycle progression, but might be associated with other mechanisms responsible for aggressive tumour behaviour in colorectal cancer.