Low p27Kip1 expression is associated with poor prognosis in oral squamous cell carcinoma

BACKGROUND: p27Kip1 is a cyclin-dependent kinase inhibitor which regulates the progression of cells from the G1-into the S-phase in a cell cycle. Loss of p27Kip1 is associated with disease progression and an unfavorable outcome in several malignancies. The purpose of this study was to determine whether p27Kip1 expression can be a useful prognostic factor in oral squamous cell carcinoma (SCC) patients. PATIENTS AND METHODS: p27Kip1 expression was investigated by immunohistochemistry in tissue samples from 81 patients with oral SCC. The associations between p27Kip1 expression and clinicopathological characteristics and patient survival were also analyzed. RESULTS: Significant associations were found between p27Kip1 expression and histological grade (p = 0.010), therapeutic effect (p = 0.004) and patient outcome (p = 0.005). The 5-year survival rates of p27Kip1 high- and low-expression tumours were 80.4% and 56.7%, respectively, this difference being significant (p = 0.009) by log-rank test. Multivariate analysis revealed that reduced term survival was related to low levels of p27Kip1 expression (p = 0.008) and advanced stage (stages III and IV) (p = 0.003). CONCLUSION: These results suggest that reduction of p27Kip1 plays an important role in the progression of oral SCC and is considered to be a useful prognostic factor in oral SCC patients.     

Loss of p27Kip1 expression independently predicts poor prognosis for patients with resectable pancreatic adenocarcinoma

BACKGROUND: As a universal inhibitor of cyclin-dependent kinases in mammalian cells, p27Kip1 expression has been implicated in tumor progression and has proved to be a prognostic predictor for several human cancers. In this study, the authors investigated the expression of p27Kip1 and its potential prognostic significance in patients with resectable pancreatic adenocarcinoma. METHODS: The correlation between p27Kip1 expression and prognosis was investigated retrospectively in 38 patients who had undergone resection of pancreatic adenocarcinoma including 2 cystadenocarcinomas and 4 mucin-producing tumors. Immunohistochemical staining using an anti-p27Kip1 antibody, along with an assessment of tumor cell Ki-67 labeling index, was performed on resected specimens. RESULTS: p27Kip1 expression in pancreatic adenocarcinoma was decreased dramatically when compared with that in normal pancreatic tissue. Based on 35 cases available for survival analysis, loss of p27Kip1 expression in 16 cases defined as having no or <1% p27Kip1 positive tumor cells showed 1-, 1.5-, and 2-year survival rates of 37.5%, 15.6%, and 0%, respectively, in comparison with 1-, 2-, and 3-year survival rates of 68.4%, 62.2%, and 49.8%, respectively, in the other cases (P = 0.001). After excluding cases of cystadenocarcinoma and mucin-producing tumors, the survival advantage for patients with p27Kip1 positive tumors remained apparent (P = 0.024). In each Cox regression model, both those including cystadenocarcinoma and mucin-producing tumors and those that did not, p27Kip1 expression proved to be an independent predictor for overall survival by multivariate analysis. CONCLUSIONS: These results reveal the significance of p27Kip1 immunostaining in predicting the outcome of patients with resectable pancreatic adenocarcinoma, adding a novel predictor in the evaluation of prognosis for this lethal disease.     

Low expression of p27(Kip1) is associated with tumor size and poor prognosis in patients with renal cell carcinoma

BACKGROUND: Proliferative activity in tumors depends on regulation of the cell cycle. p27(Kip1) (p27) plays a pivotal role as a negative regulator of the cell cycle. A decrease in p27 expression has been reported in many kinds of tumors, but little is known regarding p27 in patients with renal cell carcinoma (RCC). METHODS: Expression of p27 and the related cyclins (cyclin A, cyclin E, and cyclin D1) was examined immunohistochemically in 67 patients with of clear cell RCC. The Ki-67 labeling index (MIB-1 LI) and clinicopathologic parameters related to a poor prognosis also were analyzed. To determine their prognostic significance, univariate and multivariate survival analyses were performed. RESULTS: In tumors, there was considerable immunoreactivity for cyclin A, cyclin D1, and MIB-1, and the mean values for each were 1.08%, 16.1%, and 1.5%, respectively. Cyclin E expression was rare. The expression of p27 was correlated strongly with the expression of cyclin A (correlation coefficient, 0.432; P < 0.0004) and cyclin D1 (correlation coefficient, 0.476; P < 0.0004). Also, an inverse correlation was present between p27 expression and tumor size (P = 0.0377). In univariate analysis, the unfavorable prognostic factors were high TNM stage (P < 0.0001), large tumor size (P = 0.0016), high histologic grade (P = 0.0104), and low p27 expression (P < 0.0001). In multivariate analysis, high TNM stage (P = 0.0035) and low p27 expression (P = 0.0235) were independent prognostic factors for disease specific survival in patients with RCC. CONCLUSIONS: The results of this study suggest that low p27 expression may be a significant and independent, unfavorable prognostic factor in patients with renal cell carcinoma.     

Down-regulated p16 expression predicts poor prognosis in patients with extrahepatic biliary tract carcinomas

The prognosis of extrahepatic biliary tract cancer (EBT) patients is generally accepted to be poor. We immunohistochemically evaluated expression of p16, a cyclin-depend kinase inhibitor, in tumor specimens surgically removed from 99 EBT patients. We also examined whether there was any relationship between expression of p16 and biological malignancy of the tumor by comparing its clinicopathological factors. Consequently, we found that there were three types of p16 expression in the tumor cells; diffuse, heterogeneous and negative types, the percentages of which were 19, 41 and 39%, respectively. Heterogeneous and negative types, whose expression of p16 was considered to be down-regulated, showed scirrhous (p=0.022) and infiltrating growth (p=0.002). In addition, we found that the proportion of down-regulated expression of p16 was different, depending on the location of the tumor. We also observed that the down-regulated p16 expression was the highest in a proportion of patients with the extrahepatic bile duct carcinoma. In contrast, the proportion of down-regulated p16 expression was the least among the patients in the region of the ampulla of Vater with better prognosis, and we showed that the prognosis of patients with down-regulated expression of p16 was the poorest in terms of the cancer location where it is limited to the region of ampulla of Vater. These findings suggest that down-regulated p16 expression is evaluated as a factor of poorer prognosis and also that immunohistochemical pattern of p16 expression becomes a marker reflecting the biological malignancy of EBT patients.     

Skp2、p27Kip1在胆囊癌组织中的表达及其临床意义

目的探讨Skp2、p27Kip1在胆囊癌及癌旁组织中的表达情况及与其临床病理特征的关系。方法采用免疫组织化学PV6000二步法,检测Skp2、p27Kip1在78例胆囊癌及癌旁组织中的表达情况,并应用SPSS13.0统计软件分析2种生物指标与胆囊癌临床参数的关系。结果 Skp2与p27Kip1在胆囊癌中的阳性表达率分别为59.0%和39.7%,在癌旁组织中为25.0%和70.0%,胆囊癌中Skp2、p27Kip1阳性表达率均高于胆囊癌旁组织(P均<0.05)。Skp2表达与Nevin分期、分化程度及坏死情况相关,Nevin分期高、分化程度低及伴有坏死的患者Skp2表达高(P均<0.05)。p27Kip1阳性表达与患者Nevin分期、神经侵犯及坏死情况呈负相关性,Nevin分期早、无神经侵犯或不伴坏死患者p27Kip1表达水平高(P均<0.05)。相关性检验显示Skp2与p27Kip1两者间无相关性(P>0.05)。结论 Skp2、p27Kip1均与胆囊癌的发生发展有一定关系,可能成为胆囊癌新的临床诊断和监测预后的指标.     

胃癌中Cks1 、p27 Kip1和Skp2 蛋白的表达

 目的 探讨Cks1在胃癌发生及其在Skp2调节p27 ^Kip1降解过程中的作用。方法 应用流式细胞术测定正常胃粘膜和胃癌组织中Cks1、p27^Kip1、Skp2蛋白表达。结果胃癌组织中Cks1、Skp2表达明显高于正常胃粘膜（x²=22．69，P〈0．05；x²=13．42，P〈0．05），而p27 ^Kip1表达则低于正常胃粘膜（x²=14．83，P〈0．05）。胃癌中Cks1、Skp2表达与p27 ^Kip1表达呈负相关（r=-0．649，P〈0．05；r=-0．732，P〈0．05）；而Cks1蛋白表达与Skp2蛋白缺乏相关性（P〉0．05）。胃癌中Cks1的表达与肿瘤分化程度相关（x²=5．05，P〈0．05），而与肿瘤浸润深度、淋巴结转移及临床分期不相关（P〉0．05）。结论Cks1可能参与了胃癌的发生；胃癌中Cks1可能参与了Skp2调节p27 ^Kip1泛素化降解过程。     

Low expression of p27(Kip1), a cyclin-dependent kinase inhibitor, is a marker of poor prognosis in synovial sarcoma

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: The study results suggested that low expression of p27(kip1) may be useful as a marker of poor-prognosis synovial sarcoma.     

Skp2 overexpression is a prognostic factor in patients with ovarian adenocarcinoma.

PURPOSE: The purpose of this study was to examine Skp2 expression in epithelial ovarian tumors and to identify the association of Skp2 expression levels with patient survival. EXPERIMENTAL DESIGN: Skp2 protein expression was examined by immunohistochemistry in 134 epithelial ovarian tumors [20 adenomas, 23 low malignant potential (LMP) tumors, and 91 adenocarcinomas]. Results of immunostaining were correlated with clinicopathological variables and overall survival. Skp2 mRNA expression was examined by semiquantitative PCR in 32 ovarian adenocarcinomas and in 3 ovarian cancer cell lines. RESULTS: Skp2 expression was detected in neither ovarian adenomas nor LMP tumors. In contrast, Skp2 expression was detected in 47.3% (43 of 91) of adenocarcinomas. Positive Skp2 expression was detected significantly more often in adenocarcinomas than in LMP tumors (P < 0.0001) or in adenomas (P < 0.0001). A significantly higher detection rate of Skp2 expression was observed in advanced-stage diseases compared with early-stage diseases (P = 0.010). Log-rank testing showed that Skp2 overexpression was significantly correlated with poor patient survival (P = 0.0035). Older age (P = 0.0026), advanced clinical stage (P < 0.0001), and high histological grades of the tumors (P = 0.0018) were also significantly associated with poor prognoses. In multivariate analysis, Skp2 overexpression (P = 0.0069) and clinical stage (P < 0.0001) remained significantly associated with overall survival, whereas age and histological grade lost their significance. Considerable levels of Skp2 mRNA expression were detected in all ovarian adenocarcinomas examined by semiquantitative PCR. CONCLUSIONS: Skp2 expression might play an important role in the development and progression of ovarian adenocarcinomas, and Skp2 overexpression is an independent prognostic marker of ovarian adenocarcinoma patients.     

Aurora-A is a novel predictor of poor prognosis in patients with resected lung adenocarcinoma

Background： The Aurora-A （AurA） gene, a key regulator of mitosis, has been proved as an oncogene in a variety of cancers. The Aur-A overexpression has been proved correlated with aggressiveness of cancer cells. However, the frequency of Aur-A protein overexpression, as well as its association with clinicopathologic parameters and prognosis remain unclear in lung adenocarcinoma （ADC）. This study tried to clarify the clinical significance of Aur-A in patients with resected lung ADC. Patients and methods： A total of 142 informative patients with surgically resected lung ADC and 20 normal lung tissues were enrolled. Western blot and immunohistochemistry （IHC） were utilized to assess protein expression of Aur-A. Result： The expression of Aur-A was elevated in most of tumor tissues compared with the adjacent tissues by western blot. The IHC results showed that Aur-A protein was over-expressed in 98 of 142 （69.0%） tumor sections, while Aur-A was low-expressed in all normal lung sections. A positive correlation between Aur-A overexpression rate and ascending pathologic stages was observed （P〈0.05）. Kaplan-Meier analysis demonstrated that patients with Aur-A high expression had significantly inferior survival compared to those with Aur-A low expression. Both overall survival （OS） and disease-free survival （DFS） of positive overexpression patients were shorter than the negative group （P=0.036, P=0.041, respectively）. Multivariate analysis confirmed that Aur-A expression, as an independent and significant factor for both DFS and OS, could predict a poor prognosis in patients with resected lung ADC （P=0.022, P=0.049, respectively）. Conclusions： Aur-A was overexpressed in lung ADC and overexpression of Aur-A might be a novel predictor for poor prognosis and potential therapeutic target in lung ADC.     

Phosphorylation/cytoplasmic localization of p21Cip1/WAF1 is associated with HER2/neu overexpression and provides a novel combination predictor for poor prognosis in breast cancer patients.

PURPOSE: The diversity of biological functions makes p21(Cip1/WAF1) (p21) a controversial marker in predicting the prognosis of breast cancer patients. Recent laboratory studies revealed that the regulation of p21 function could be related to different subcellular localizations of p21 by Akt-induced phosphorylation at threonine 145 in HER2/neu-overexpressing breast cancer cells. The purpose of this study was to verify these findings in clinical settings. EXPERIMENTAL DESIGN: The expression status of the key biological markers in the HER2/neu-Akt-p21 pathway in 130 breast cancer specimens was evaluated by immunohistochemical staining and correlated with patients' clinical parameters and survival. In addition, an antibody against phospho-p21 at threonine 145 [phospho-p21 (T145)] was also used for better validation of these findings. RESULTS: Cytoplasmic localization of p21 is highly correlated with overexpression of phospho-p21 (T145). Both cytoplasmic p21 and overexpression of phospho-p21 (T145) are associated with high expression of HER2/neu and phospho-Akt. Cytoplasmic localization of p21 and overexpression of phospho-p21 (T145), HER2/neu, and phospho-Akt are all associated with worse overall survival. Multivariate analysis of the Cox proportional hazard regression model revealed that cytoplasmic p21 and overexpression of HER2/neu are independently associated with increased risk of death. Combining these two factors stratified patients' survival into four distinct groups, with a 5-year survival rate of 79% in low HER2/neu and negative/nuclear p21 patients, 60% in high HER2/neu and negative/nuclear p21 patients, 29% in low HER2/neu and cytoplasmic p21 patients, and 16% in high HER2/neu and cytoplasmic p21 patients. CONCLUSIONS: The present study, in addition to supporting the mechanisms of p21 regulation derived from laboratory investigation, demonstrates the prognostic importance of phospho-p21 (T145) for the first time and also provides a novel combination of p21 and HER2/neu for better stratification of patients' survival than any single clinicopathological or biological marker that may play important diagnostic and therapeutic roles for breast cancer patients.     

Low expression of p27 indicates a poor prognosis in patients with high-grade astrocytomas

BACKGROUND: Two families of tumor suppressor genes, Cip/Kip (p21, p27, and 57) and INK4 (p15, p16, p18, and p19), regulate cell proliferation and neoplastic transformation. p27 exerts its suppressor effect through cyclin E-dependent kinase (CDK2) by inhibiting the phosphorylation of pRb by CDK2, which, in turn, arrests cells in the G1-phase. p21 has a similar effect in addition to participating in the p53 dependent CDK4-mediated and CDK6-mediated pathway. The authors studied the prognostic significance of p21 and p27 in patients with high-grade astrocytomas who were treated with radiotherapy. METHODS: The expression of p27 and p21 was analyzed immunohistochemically in 52 glioblastomas and 25 anaplastic astrocytomas. All patients underwent surgery for the first time and were treated with adjuvant external radiotherapy. RESULTS: The p27 labeling index (LI) was < 30% in 36% of tumors, 30-50% in 25% of tumors, and > 50% in 39% of tumors. A significant difference in cumulative survival was observed between these groups (P = 0.0072; log-rank test). The p21 LI was < 30% in 48% of tumors, 30-50% in 39% of tumors, and > 50% in 13% of tumors; these groups did not differ significantly in survival. In multivariate Cox analysis, p27 LI was an independent prognostic factor (P = 0.0008). The grade of malignancy and proliferation activity also were independent prognostic factors. CONCLUSIONS: Although p27 and p21 are parallel cell-cycle regulators, only p27 has independent prognostic value in patients with malignant astrocytomas. It appears that decreased levels of p21/p27 are associated with a poor prognosis and short survival.     

Skp2 and Jab1 expression are associated with inverse expression of p27(KIP1) and poor prognosis in oral squamous cell carcinomas

Previous studies have shown that low levels of p27(KIP1), an inhibitor of G1 cyclin-dependent kinases (CDK), are associated with high aggressiveness and poor prognosis in a variety of cancers. Decreased levels of p27(KIP1) are caused, at least in part, by an acceleration of degradation with Skp2 (S-phase kinase-associated protein 2) and Jab1 (Jun activation domain-binding protein 1). This investigation was undertaken to examine whether the Skp2 and Jab1 expression is correlated with p27(KIP1) protein levels, and how it is clinically relevant in oral squamous cell carcinoma (OSCC). The correlations between p27(KIP1) and Skp2, and p27(KIP1) and Jab1 expression were evaluated by Western blot analysis. Immunohistochemical analysis was done in 75 cases of OSCC. A strongly significant inverse correlation was found between levels of p27(KIP1) and Skp2, and p27(KIP1) and Jab1 (p < 0.0001). Thus, decreased levels of p27(KIP1) were associated with strongly increased levels of Skp2 and Jab1, whereas high levels of p27(KIP1) coincided with low levels of Skp2 and Jab1. Reductions of p27(KIP1) expression and overexpression of Skp2 and Jab1 were significantly associated with cervical lymph node metastasis and poor prognosis. Overexpression of Skp2 and Jab1 is associated with the reduction of p27(KIP1) expression, and may have a role in the progression of OSCC.     

Astrocyte-elevated gene-1 overexpression is associated with poor prognosis in gastric cancer

Astrocyte-elevated gene-1 (AEG-1) plays an important role in diverse cancers and its up-regulation is associated with poor survival of patients. However, the status of AEG-1 expression and its significance in gastric cancer are still unclear. In this study, the expression of AEG-1 was studied in different gastric cancer cell lines and gastric cancer tissues. Expression of AEG-1 was significantly higher in gastric cancer tissues than that in normal tissues. Overexpression of AEG-1 was found in 62.9% of gastric cancers and significantly associated with TNM stage and Ki-67 proliferation index (P < 0.01). For survival study, overexpression of AEG-1 was significantly associated with poor survival (P < 0.01). Further multivariate analysis suggested that AEG-1 overexpression was an independent prognostic factor for the disease. We demonstrated that inhibition of AEG-1 expression by specific siRNA clearly inhibited SGC-7901 cell growth and enhanced cell apoptosis (P < 0.01). Inhibition of AEG-1 reduced phosphorylation of AKT and glycogen synthase kinase (GSK)-3β (Ser 9) and decreased the level of β-catenin, lymphoid enhancer binding factor 1 (LEF1), and Cyclin D1. This indicated that AEG-1 may play a role in Wnt/β-catenin-mediated cancer progression. Taken together, overexpression of AEG-1 could be a useful prognostic factor in patients with gastric cancer. Targeted inhibition of AEG-1 may provide a novel therapeutic strategy for gastric cancer.     

Prognostic implication of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma: a tissue microarray study

Background

p27^Kip1 plays a major role as a negative regulator of the cell cycle. The regulation of p27^Kip1 degradation is mediated by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. However, little is known regarding the prognostic utility of p27^Kip1, Skp2 and Cks1 expression in renal cell carcinoma.

Methods

Immunohistochemistry was performed for p27^Kip1, Skp2 and Cks1 in tissue microarrays of 482 renal cell carcinomas with follow-up. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance.

Results

Immunoreactivity of p27^Kip1, Skp2 and Cks1 was noted in 357, 71 and 82 patients, respectively. Skp2 and Cks1 expression were not noted in chromophobe cancers. A strong correlation was found between Skp2 and Cks1 expression (P < 0.001), both of which were inversely related to p27^Kip1 levels (P = 0.006 and P < 0.001), especially in primary and clear-cell cancers. Low p27^Kip1 expression and Skp2 expression were correlated with larger tumor size and higher stage, as well as tumor necrosis. Cks1 expression was only correlated with tumor size. In univariate analysis, low p27^Kip1 expression, Skp2 and Cks1 expression were all associated with a poor prognosis, while in multivariate analysis, only low p27^Kip1 expression were independent prognostic factors for both cancer specific survival and recurrence-free survival in patients with RCC.

Conclusion

Our results suggest that immunohistochemical expression levels of p27^Kip1, Skp2 and Cks1 may serve as markers with prognostic value in renal cell carcinoma.     

Cytoplasmic mislocalization of p27Kip1 protein is associated with constitutive phosphorylation of Akt or protein kinase B and poor prognosis in acute myelogenous leukemia

Cyclin-dependent kinase inhibitor p27Kip1 functions at the nuclear level by binding to cyclin E/cyclin-dependent kinase-2. It was shown that Akt or protein kinase B (Akt/PKB)-dependent phosphorylation of p27Kip1 led to the cytoplasmic mislocalization of p27Kip1, suggesting the potential abrogation of its activity. Here, we evaluated the localization of p27Kip1 protein in leukemic blasts in relation to Akt/PKB phosphorylation and clinical outcomes in acute myelogenous leukemia (AML). Western blot analysis of the nuclear and cytoplasmic fractions revealed a heterogenous localization pattern of p27Kip1 in AML. Cytoplasmic mislocalization of p27Kip1 was significantly associated with the constitutive serine(473) Akt/PKB phosphorylation in AML cells (P < 0.05). Transfection of U937 cells with an expression construct encoding the constitutively active form of Akt/PKB resulted in a remarkable increase in the levels of cytoplasmic p27Kip1. Whereas the transfection of U937 cells with a construct encoding dominant-negative Akt/PKB resulted in a recovery of nuclear localization of p27Kip1. Both the disease-free survival and overall survival are significantly shorter in AML cases with high cytoplasmic to nuclear ratio of p27Kip1 localization compared with the cases with low cytoplasmic to nuclear ratio (P = 0.0353, P = 0.0023, respectively). Multivariate analysis indicated that the cytoplasmic to nuclear ratio of p27Kip1 localization was an independent prognostic variable for both disease-free survival and overall survival (P = 0.043, P = 0.008, respectively). These findings additionally extend our understanding of the role of p27Kip1 in AML, and buttress the case of p27Kip1 mislocalization as a prognostic indicator and Akt/PKB/p27Kip1 pathway as a ready target for antileukemia therapy.     

High expression of Pirh2, an E3 ligase for p27, is associated with low expression of p27 and poor prognosis in head and neck cancers

Downregulation of the cyclin-dependent kinase inhibitory protein p27 is frequently observed in various cancers due to enhancement of its degradation. We recently reported that p53-inducible protein with RING-H2 domain (Pirh2) is a novel ubiquitin ligase for p27, required for the ubiquitylation and consequent degradation of p27 protein. However, there is no reports about the involvement of Pirh2 in both p27 downregulation and pathogenesis in human cancers. In the present study, we investigated them using cultured cell lines and surgical specimens derived from human head and neck squamous cell carcinoma (HNSCC). Depletion of Pirh2 by short interfering RNA induced accumulation of p27 and inhibited the growth of cultured HNSCC cells. By immunohistochemical analysis in 57 cases of HNSCC specimens, higher levels of Pirh2 expression (labeling index ≥ 60%) were found in 61.4% of HNSCC in comparison with 0% of normal mucosa. In addition, 83.3% of HNSCC with lower p27 expression (labeling index < 20%) displayed high Pirh2 levels. Therefore, Pirh2 expression was inversely correlated with p27 expression. Finally, Pirh2 expression was well correlated with poor prognosis. These findings suggest that Pirh2 overexpression may have an important role in the development and maintenance of HNSCC at least partially through p27 degradation, and that Pirh2 may be a potential molecular target for human HNSCC. ( Cancer Sci 2009; 100: 866–872)