Prognostic Value of PCNA and Mutant p53 Expression in Laryngeal Squamous Cell Carcinoma

The objective of this study was to investigate the prognostic significance of p53, and proliferative cell nuclear antigen (PCNA) in laryngeal squamous cell carcinoma (LSCC). Sixty pathologic specimens from the patients with LSCC were examined for the expression of the p53 and PCNA, with complete follow-up data. Sixty-three percent of the cases displayed nuclear p53 overexpression. There was a correlation between p53 overexpression and histological grades (p = 0.03), and localization site (p = 0.05). Median of PCNA index was 42.2 (range 5.9 to 85.2). There was no difference between the p53 overexpression group and the normal group in proliferative activity determined by PCNA (p = 0.73). In univariate analyses, localization site, grade, stage, invasion pattern, lymph node status, were significant factors in estimating disease free survival (DFS). Grade was the most important factor affecting recurrence (p = 0.002). In multivariate analyses, grade was the only significant predictor for DFS (p = 0.001). Grade (p = 0.001) and invasion pattern (p = 0.03) were found to be significant predictors of overall survival. In conclusion, the histological grade was the most reliable important prognostic factor. Further studies are necessary to facilitate understanding of the mechanisms of laryngeal carcinogenesis.     

Prognostic significance of cyclin E overexpression in laryngeal squamous cell carcinomas.

Cyclin E plays a pivotal role in the regulation of G1-S transition and relates to malignant transformation of cells. However, the clinical significance of cyclin E in patients with laryngeal squamous cell carcinoma (LSCC) remains unknown. We examined the expression of cyclin E in 102 patients with LSCC and analyzed its relation to clinicopathological parameters, cell proliferation, and clinical outcome. Cyclin E overexpression was observed in 54 cases (52.94%) of LSCC and was significantly correlated with the tumor site (P = 0.012), tumor size (P = 0.006), poor differentiation (P = 0.026), lymph node metastasis (P = 0.012), and advanced stage (P = 0.002). A positive correlation between the cyclin E expression and proliferative activity of tumor cells was found (r = 0.896; P < 0.0001). Kaplan-Meier analysis showed that shorter disease-free and overall survival was significantly associated with proliferating cell nuclear antigen (PCNA) overexpression and cyclin E overexpression. When PCNA and cyclin E are combined, the patients with both PCNA overexpression and cyclin E overexpression had the poorest prognoses when compared with the other cases. Additionally, in early stage (I-II) cases, cyclin E was also revealed to possess a significant prognostic role. By multivariate analysis, lymph node metastasis and cyclin E overexpression were independent prognostic factors for disease-free survival, and tumor size, lymph node metastasis, advanced stage, as well as cyclin E overexpression were independent prognostic factors for overall survival. These findings indicate that cyclin E overexpression is associated with unfavorable clinicopathological parameters and represents an independent marker for cell proliferation and prognosis of LSCC.     

P53 and PCNA is Positively Correlated with HPV Infection in Laryngeal Epitheliopapillomatous Lesions in Patiets with Different Ethnic Backgrounds in Xinjiang

Objective: To explore the correlation of human papillomavious (HPV) infection with expression of p53 andproliferating cell nuclear antigen (PCNA) in patients with different ethnicity in Xinjiang, China. Methods: 166biopsy specimens from 83 laryngeal squamous cell carcinomas (LSCC), 63 laryngeal papillomas (LP), and 20laryngeal inflammatory polyps (LIP) were included in this study. HPV infection was determined by polymerasechain reaction (PCR) using specific types of HPV primers. Expression of p53 and PCNA was assessed usingimmunohistostaining. Results: The frequency of HPV 6/11 was higher in LP (33.3%) than in LSCC (9.6%) (P<0.0005), whereas the frequency of HPV 16/18 was higher in LSCC (37.3 %) than in LP (6.3%) (P < 0.0005).Patients of the Han ethnic group with LSCC had a higher infection rate with HPV 6/11 or HPV 6/11 and HPV16/18 coinfection than those of Uygur and Kazak ethnicity (P <0.05). Overexpression of p53 and PCNA were higherin LSCC (62.7%, 57.8%) than in LP (38%, 33.3%) (P <0.005, and P <0.005, respectively). That of p53 was notassociated with lymph-node metastases and clinical stages, but overexpression of PCNA closely correlated withclinical stage. Conclusions: These results strongly implicate HPV6/11 infection in the carcinogenesis of LSCC andLP, respectively. There was a higher coincidence of increased malignancy of laryngeal tumors with overexpressionof p53 and PCNA. Overexpression of p53 may serve as an early risk marker for malignant transformation inHPV infected cells while the overexpression of PCNA may serve as a late marker for progression of LSCC.     

Overexpression of p53 protein is an independent prognostic indicator in human endometrial carcinoma.

The important role of the p53 gene in tumour progression and cellular response to DNA damage has prompted investigation of the clinical significance of alterations to this gene. We examined both p53 overexpression and mutation of the gene in endometrial carcinoma in order to evaluate the prognostic significance of these changes. Of 122 endometrial carcinomas, 33 (27%) showed overexpression of p53 in the nucleus and 66 (54%) in the cytoplasm. Mutation in the p53 gene was found in 16 (13%) cases but showed no significant association with patient survival. Nuclear p53 overexpression was associated with poor survival (48% vs 80% alive in negative tumours 5 years post operatively, P < 0.001). In contrast, cytoplasmic p53 overexpression was associated with better survival (85% vs 55%, P < 0.001). When patients were separated into prognostic subgroups according to established clinical markers, these associations remained significant within most subgroups examined. In multivariate analysis adjusted for surgical stage, histological grade and type and vascular invasion, both nuclear p53 overexpression [hazard ratio 4.9 (95% CI 1.3-17.6). P = 0.016] and cytoplasmic overexpression [0.25 (0.06-0.98), P = 0.047] were independent prognostic factors. Immunohistochemical assessment of p53 overexpression in the nucleus and cytoplasm could provide useful prognostic information for the management of patients with endometrial cancer.     

Cyclin D1-CDK4 complex, a possible critical factor for cell proliferation and prognosis in laryngeal squamous cell carcinomas

Cyclin D1 and its catalytic partner CDK4 are known to play important roles in the G1/S checkpoint of the cell cycle. The complex formed by CDK4 and cyclin D1 has been strongly implicated in the control of cell proliferation and prognoses in human malignancies. We investigated the immunohistochemical expression of cyclin D1, CDK4 and proliferating cell nuclear antigen (PCNA) in 102 patients with laryngeal squamous cell carcinoma (LSCC). Cyclin D1 overexpression was observed in 59 cases (57.8%) of LSCC, and was significantly correlated with tumor site, tumor size, lymph node metastasis and advanced stage. CDK4 overexpression was observed in 48 cases (47.1%), and was significantly correlated with tumor size and advanced stage. Cyclin D1 and CDK4 expression was significantly associated with cell proliferation measured by PCNA (r = 0.812, p < 0.0001 and r = 0.725, p < 0.0001, respectively). The Kaplan-Meier analysis showed that cyclin D1 overexpression was significantly associated with disease-free survival and overall survival. CDK4 overexpression was significantly associated with overall survival. When cyclin D1 and CDK4 are combined, the patients with co-overexpression of cyclin D1-CDK4 revealed the poorest overall survival. Additionally, in early-stage (I-II) cases, co-overexpression of cyclin D1-CDK4 was also revealed to possess a significant prognostic role. By multivariate analysis, cyclin D1 overexpression, lymph node metastasis and advanced stage were independent prognostic factors for disease-free survival. Cyclin D1 overexpression, CDK4 overexpression, tumor grade, lymph node metastasis and advanced stage were independent prognostic factors for overall survival. These findings indicate that cyclin D1 and CDK4 overexpression and/or co-overexpression of these proteins may play a pivotal role in the biological behavior of LSCC and may provide a strong prognostic implication.     

P53 overexpression correlates with proliferative activity and prognosis in carcinomas of the pyriform sinus

p53 overexpression and proliferative activity were investigated in 28 squamous cell carcinomas of the pyriform sinus of the hypopharynx prior to therapy, using DO1 and MIB-1 monoclonal antibodies in routinely processed biopsies. MIB-1 scores were associated with tumour histological grade (35.4% for grade 3 versus 23.8% for grade 2 cases; p=0.008) and survival (the median of survival was 23 months for cases with MIB-1 scores less than or equal to 33.8% but 11 months only for cases with MIB-1 scores >33.8%; p<0.001). p53 scores were associated with tumour histological grade (56.5% for grade 3 versus 37.1% for grade 2 cases; p=0.02) and survival (median of survival 20 months for cases with p53 scores less than or equal to 56.2% versus 11 months for cases with p53 scores >56.2%; p=0.002). Tumour histological grade was also correlated with prognosis (median of survival 50 months for grade 2 versus 14 months for grade 3 cases; p=0.03). In the multivariate analysis, only MIB-1 (p=0.001) and p53 scores (p=0.003) had an independent prognostic significance. A linear relationship between p53 and MIB-1 scores was observed (r=0.54; p=0.012). With the limitation due to the small number of cases, our findings indicate that p53 overexpression correlates with proliferative activity and survival in squamous cell carcinomas of the pyriform sinus, and suggest the use of p53 and MIB-1 immunostainings in the pretherapeutic assessment of the tumour aggressiveness.     

Prognostic implication of p53 protein expression in relation to nuclear pleomorphism and the MIB-1 counts in breast cancer

BACKGROUND: A close correlation of the p53 protein expression to nuclear pleomorphism and proliferative activity in breast cancer has been reported. The prognostic implications of p53 protein expression, however, in relation to nuclear pleomorphism and proliferative activity in breast cancer remain controversial. PATIENTS AND METHODS: Nuclear pleomorphism and immunohistochemical reactivity for p53 protein and MIB-1 were evaluated on formalin-fixed paraffin-stored sections from 250 patients with breast cancer for whom the median follow-up duration was 6.4 years. RESULTS: p53 protein expression was positive in 66 (26.4%) of 250 cases. Nuclear pleomorphism was grade I or II in 169 (67.6%) cases and grade III in 81(32.4%)cases. The MIB-1 counts were more than 10% in 102 (40.8%) cases and less than 10% in 148 (59.2%) cases. There was a close correlation between p53 protein expression and nuclear pleomorphism (p<0.0001) and between p53 protein expression and MIB-1 counts (p<0.0001). Univariate analyses showed the 66 cases with positive p53 protein expression to have a significantly (p=0.0284) worse disease free survival (DFS) than the 184 cases with negative p53 protein expression. A multivariate analysis, however, on the variables including all of p53 protein expression, nuclear pleomorphism and MIB-1 counts indicated the MIB-1 counts (p=0.0041) as well as the lymph node status to be independently significant factors for DFS, while neither p53 protein expression nor nuclear pleomorphism were independently significant factors for DFS. CONCLUSION: The present study demonstrated that the p53 protein expression, nuclear pleomorphism and MIB-1 counts all demonstrated prognostic significance for breast cancer, while the most significant prognostic indicator among these three biological parameters was the MIB-1 counts.     

p53 expression in dedifferentiated chondrosarcoma

Background. p53 acts as a tumor suppressor gene because of to its negative control of the cell cycle and its central role in programmed cell death. It frequently is mutated, as observed in a variety of human neoplasms. The mutations inhibit tumor-suppressor activities of p53, which may gain a new function of tumor promotion. In this study, p53 was investigated in various components of dedifferentiated chondrosarcoma and correlated with their proliferative activities. Methods. Immunohistochemical assays for p53, Ki-67, and proliferating cell nuclear antigen (PCNA) were used in a series of eight dedifferentiated chondrosarcomas of bone. The cartilaginous component was low grade (Grade I-II) in five cases. It was predominantly low grade with foci of a high grade (Grade III) chondrosarcoma in the remaining three cases. The noncartilaginous (de-differentiated) high grade component consisted of malignant fibrous histiocytoma in five cases and osteosarcoma in three. Results. Regardless of the histological type, diffuse strong nuclear staining for p53 occurred in the high grade noncartilaginous component of all eight of the tumors. The low grade cartilaginous component of six cases was negative for p53, with focal weak staining in the two remaining cases. The high grade cartilaginous component showed strong positive staining for this protein in all three cases. Ki-67 and PCNA expression were similar to that of p53. Conclusions. The percentage of p53 positive staining roughly was parallel to the proliferating fraction of cells in various components of dedifferentiated chondrosarcoma. Moreover, p53 overexpression was consistently present in the high grade noncartilaginous (dedifferentiated) component of the tumor and was accompanied by increased proliferative activity. Cancer 1995; 76:223-7.     

癌蛋白iASPP在喉鳞癌中的表达及临床意义

目的:从蛋白及mRNA水平检测iASPP在喉鳞癌组织中的表达,并研究其表达与喉鳞癌患者临床病理特征及预后的关系。方法:采用免疫组化方法检测99例喉鳞癌和15例癌旁黏膜组织中癌蛋白iASPP的表达,统计分析iASPP的表达与喉鳞癌患者临床病理特征和预后的关系;采用荧光定量RT-PCR检测13例配对喉鳞癌及癌旁组织中iASPP mRNA的表达情况。结果:癌蛋白iASPP在喉鳞癌细胞的胞浆及胞核中均有表达,且iASPP蛋白及mRNA在喉鳞癌组织和癌旁黏膜组织中的表达有显著性差异(P＜0.01)。胞浆iASPP蛋白和胞核iASPP蛋白的表达与喉鳞癌患者的T分期(P=0.001,P=0.021)、临床分期(P=0.001,P=0.010)、淋巴结转移(P=0.001,P=0.003)和复发(P＜0.001,P=0.001)具有显著的相关性。Kaplan-Meier生存分析结果表明,胞浆iASPP蛋白高表达组和低表达组、胞核iASPP蛋白高表达组和低表达组的5年无病生存率和5年总生存率间具有显著性差异(P均<0.01)。进一步用多因素Cox比例风险回归模型分析显示,胞浆iASPP表达水平是喉鳞癌患者预后的独立影响因素(P＜0.01)。结论:癌蛋白iASPP在喉鳞癌组织中的表达显著上调,且与喉鳞癌患者的T分期、临床分期、淋巴结转移和复发密切相关。iASPP可能在喉鳞癌的发生发展中起着重要作用,并有望成为预测和评估喉鳞癌患者预后的重要分子标志物和潜在的治疗靶点。     

p53、c-erbB2基因、增殖细胞核抗原表达与卵巢上皮性癌预后的关系

背景与目的：p53、c-erbB2基因和增殖细胞核抗原（proliferating cell nuclear antigen,PCNA)的表达与卵巢癌预后关系问题已有报道,由于研究方法、样本大小等方面的不同,结果存在差异。为进一步探讨p53、c-erbB2基因和PCNA表达与卵巢上皮性癌预后的关系,我们进行了本研究。材料与方法：1990年3月1日至1994年3月31日间确诊的卵巢上皮性癌共84例,采用标记的链白素－生物素辣根过氧化酶复合物（LSAB）免疫组化方法检测癌组织中p53、c-erbB2基因和PCNA的表达,使用SPSS8．0版分析它们的表达与卵巢癌患者平均生存期、5年生存率之间的关系。结果：本组84例癌组织中,p53、c-erbB2和PCNA表达的阳性率分别为58．3％（49／84）、77．5％（65／84）和100％（84／84）。单因素分析显示,c-erbB2过度表达和PCNA表达强度与患者的平均生存期、5年生存率均呈负相关（P值分别为0．05和小于0．01）,未发现p53蛋白表达与患者的平均生存期、5年生存率之间存在相关性（P＞0．05）。多因素分析发现卵巢上皮性癌的预后与临床分期、组织分化程度有关,而与p53、c-erbB2和PCNA的表达均无相关性。结论：p53的表达与卵巢上皮性癌的预后无关,而c-erbB2、PCNA表达对卵巢上皮性癌预后的影响是间接的。临床分期、组织分化程度仍是卵巢上皮性癌独立的预后因素。     

喉鳞癌组织中p53蛋白的表达及其临床意义

目的　探讨p5 3蛋白在喉鳞状细胞癌组织中的表达及其临床意义。方法　采用免疫组化技术检测p5 3蛋白在喉鳞癌、癌旁非典型增生组织及正常组织中的表达。结果　p5 3蛋白在喉鳞癌、癌旁和正常组织中阳性表达率分别为 5 3 .7%、3 8.1%和0 ,三者有显著性差异 (P <0 .0 5 ) ;重度非典型增生组织与中、轻度增生、癌旁单纯增生和癌旁正常黏膜 p5 3阳性表达分别有显著性差异 ,表达率分别为 68.8%、2 1.4%、16.7%、8.3 %和 0 ;在肿瘤浸润的前沿部 p5 3阳性表达显著强于浅表部 (P <0 .0 5 ) ;且癌巢边缘 p5 3表达显著强于中央部 (P <0 .0 5 ) ;p5 3阳性表达与喉鳞癌的分化、淋巴结转移有关 (P <0 .0 5 )。 结论　p5 3的过度表达可能为喉鳞癌的早期发生事件 ,癌旁组织中已发生p5 3基因突变的细胞可能是肿瘤复发的根源 ;p5 3表达与喉鳞癌的浸润生长、分化及转移有关 ,为判断预后的 1个有意义指标。     

喉鳞癌组织中Bcl—2和P53蛋白表达及意义

为了探讨ｂｃｌ－２，Ｐ５３在喉鳞癌组织中的表达情况，预后的意义，我们应用免疫组化ＬＳＡＢ法对５３例喉鳞状上皮细胞癌组织进行ｂｃｌ－２，Ｐ５３基因蛋白表达的测定。结果显示：（１）４７．１７％的喉癌中检出突变型Ｐ５３蛋白，在部分喉癌旁不典型增生上皮中可见Ｐ５３蛋白表达，癌旁组织细胞已发生Ｐ５３基因突变可能是术后复发的根源，突变型Ｐ５３蛋白过度表达是喉癌发生的早期事件。     

Clinicopathologic study associated with long-term survival in Japanese patients with node-negative breast cancer

This study was undertaken to determine the absolute and relative value of blood vessel invasion (BVI) using both factor VIII-related antigen and elastica van Gieson staining, proliferating cell nuclear antigen (PCNA), p53, c-erbB-2, and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including PCNA, p53, c-erbB-2 using permanent-section immunohistochemistry, clinical tumour size (T), histological grade (HG), mitotic index (MI), tumour necrosis (TN), lymphatic vessel invasion (LVI) and BVI, followed for a median of 10 years (range 1-20). Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that BVI, PCNA, T, HG, MI, p53, c-erbB-2 and LVI were significantly predictive of 20-year RFS or OS. Multivariate analysis showed that BVI (P = 0.0159, P = 0.0368), proliferating cell nuclear antigen (PCNA) (P = 0.0165, P = 0.0001), and T (P = 0.0190, P = 0.0399) were significantly independent prognostic factors for RFS or OS respectively. BVI, PCNA and T were independent prognostic indicators for RFS or OS in Japanese patients with node-negative breast cancer and are useful in selecting high-risk patients who may be eligible to receive strong adjuvant therapies.     

p53 overexpression as a prognostic factor for advanced stage bladder cancer

Overexpression of the TP53 gene protein detected by immunohistochemistry appears to identify those patients with superficial bladder cancer at risk of the development of muscle invasive or metastatic disease. However, the role of p53 overexpression in patients with advanced or metastatic bladder cancer is not yet well established. In the present study, 44 specimens from 44 patients with advanced stage bladder tumours (T₂–T₄) undergoing radical cystectomy were investigated for different biological and clinical characteristics as possible prognostic factors: sex, age, depth of tumour infiltration, T-stage, histological grade, lymph node status, application of adjuvant systemic chemotherapy (MVAC), proliferative activity (staining for proliferating cell nuclear antigen (PCNA) by monoclonal antibody (PC10) as well as overexpression of the p53 oncoprotein (monoclonal antibody pAb 1801)). After a median follow-up of 22 months, 16 of the 23 patients (70%) with more than 40% of tumour cells stained positively for p53 (Group B) died from tumour progression compared with 7 of the 21 patients (33%) with less than 40% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.008), staining for PCNA (80% of cells positive) (P = 0.01) and tumour stage (P = 0.01) were significant prognostic factors for survival, among which p53 overexpression (P = 0.023) as well as T-stage (P = 0.012) remained independent significant predictors during multivariate analysis. Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with advanced bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for prognostically defined subgroups of patients.     

Prognostic and predictive value of changes in tumour cell proliferation in locally advanced breast cancer primarily treated with doxorubicin

We previously reported that high tumour cell proliferation evaluated by Ki-67 expression, high mitotic frequency and high histological grade were associated with resistance to primary doxorubicin monotherapy in locally advanced breast cancer harbouring wild-type (wt) TP53. The aim of our present study was to evaluate the predictive and prognostic impact of proliferation parameters assessed in tumour tissue obtained after chemotherapy, and alterations induced in tumour cell proliferation. While we found a significant reduction in Ki-67 expression and mitotic frequency in tumours with wtTP53 (p=0.001 and p=0.008, respectively), no significant change was recorded in tumours expressing mutant TP53. For histological grade there was no significant change in either group. There was a direct correlation between pre- and post-treatment values for Ki-67 and mitotic frequency in tumours harbouring wtTP53 (p=0.0001 for both), but no correlation in tumours harbouring mutated TP53. High post-treatment Ki-67 expression and mitotic frequency were found to predict doxorubicin resistance only in patients with wtTP53 (p=0.04 and p=0.03, respectively). The prognostic importance of proliferation markers and histological grade was found to be similar whether they were determined in the pre- or post-treatment samples (Ki-67; pre: p=0.02; post: p=0.03; mitotic frequency; p=0.002 and p=0.01, respectively; histological grade; p=0.0001 and p=0.002, respectively). While the reduction in mitotic frequency was associated with improved survival (p=0.03), no significant associations between changes in other parameters and outcome were recorded.     

Biologic behavior of and p53 overexpression in multifocal renal cell carcinoma of clear cell type: an immunohistochemical study correlating grading, staging, and proliferation markers

BACKGROUND: In the treatment of small renal cell carcinoma (RCC), there is controversy between radical and nephron-sparing surgical treatment because of the risk of tumor multifocality. The biologic behavior of multifocal RCC compared with that of unifocal RCC is not well investigated, and the relevance of p53 and the proliferation markers MIB-1 and proliferating cell nuclear antigen (PCNA) to multifocal RCC is not yet established. METHODS: In this study, p53 protein overexpression was investigated immunohistochemically in 27 multifocal and 65 unifocal clear cell RCCs using a monoclonal antibody (DO-1). The nuclear expression of p53 was compared with the expression of PCNA and MIB-1 (Ki-67 antigen) and other prognostic factors, including grade and stage. RESULTS: Thirty-three RCCs (35.9%) had p53 positive nuclear staining. MIB-1 positivity was significantly higher in p53 positive tumors than in p53 negative tumors. PCNA positivity was not different in p53 positive tumors compared with p53 negative tumors. Proliferation marker expression was not associated with tumor focality. p53 overexpression was more often found in unifocal tumors than in multifocal tumors. Intracellular accumulation of the p53 protein was related to tumor grade but not to the T classification of tumor stage. In addition, lymph node involvement was significantly associated with p53 overexpression in tumors of the kidney. Focality did not influence progression free survival. CONCLUSIONS: This study demonstrated that there is no difference in the proliferative activity or biologic behavior of multifocal and unifocal tumors.     

Cellular manifestations of human papillomavirus infection in laryngeal tissues

BACKGROUND AND OBJECTIVES: Although epidemiologic studies have suggested human papillomavirus (HPV) to be an etiological agent in laryngeal carcinogenesis, little is known on the cellular manifestations of HPV infection in these tumors. In this study, we investigated the frequency of HPV infection in various neoplastic and non-neoplastic laryngeal tissue and its association with expression of the proliferating cell nuclear antigen (PCNA) and the tumor suppressor protein p53. METHODS: Tissues were analyzed by polymerase chain reaction (PCR) for the presence of HPV and by immunocytochemistry for the expression of p53 and PCNA. RESULTS: None of the six normal laryngeal tissues showed the presence of HPV. Thirteen out of the 16 papillomas were positive for HPV, while 15 out of the 44 invasive cancers were HPV positive. PCNA expression increased as the lesion progressed through increasing histological abnormality (r = 0.64400, P = 0.00000). The correlation between the type of laryngeal neoplasm and p53 accumulation was significant (r = 0.54839, P = 0.00000). Significant correlation was also evident between presence of HPV and p53 accumulation (r = 0.34259, P = 0.00424) and PCNA expression (r = 0.036024, P = 0.00266) indicating that HPV positive tumors showed significant p53 accumulation and increased proliferation.There was also correlation between p53 and PCNA expression (r = 0.67475, P = 0.00000) indicating that in all tumors with p53 accumulation, there was a corresponding increase in PCNA expression. CONCLUSIONS: The results suggests that changes in p53 and PCNA expression may be associated with HPV infection, and could play a role in laryngeal carcinogenesis.     

mTOR expression and prognosis in elderly patients with laryngeal carcinoma: uni- and multivariate analyses

Cancer is common in the elderly, who may also be frail, which can complicate the choice of the best therapeutic approach. We sought to examine whether the serine-threonine kinase mTOR, a "master switch" in cancer cells that modulates metabolism, the cell cycle, and apoptosis, might help in clinical decision-making. The aim of the present study was thus to assess the potential prognostic role of mTOR in elderly patients with laryngeal carcinoma (LSCC). mTOR expression was determined immunohistochemically in 54 consecutive elderly (≥65 years old) patients with LSCC. On univariate analysis, nodal involvement and pathological stage correlated strongly with the elderly LSCC patients' prognosis in terms of disease recurrence rate and disease-free survival (DFS). Patients whose mTOR expression was >35.3% had a significantly higher recurrence rate (p=0.003) and shorter DFS (p=0.013). In the multivariate model, N status (p=0.001) and mTOR expression (p=0.026) maintained an independent prognostic significance in relation to DFS. mTOR probably influences the aggressive LSCC phenotype in elderly patients and its expression in elderly LSCC cases can be considered a prognostic marker potentially useful for identifying patients at higher risk of disease recurrence, and N0 patients at higher risk of recurrence who may benefit from more aggressive treatment. Since rapalogs (as mTOR inhibitors) might have an effect on LSCC, further investigations are needed to ascertain these agents' role in therapeutic strategies for advanced LSCC in elderly patients.     

喉鳞状细胞癌中SIAH2表达的预后价值

  目的  观察E3泛素连接酶SIAH2在喉鳞状细胞癌组织中的表达, 探讨其在喉鳞状细胞癌中表达的预后价值。  方法  应用免疫组织化学染色法检测119例喉组织标本SIAH2的定性表达, Western blot方法检测喉新鲜组织中SIAH2的定量表达, 结合患者5年随访资料, 利用Kaplan-Meier法绘制生存曲线, Log-rank法分析SIAH2的表达水平与喉鳞状细胞癌患者预后的关系, Cox比例风险回归模型分析喉鳞状细胞癌患者预后的独立预测因素。  结果  SIAH2在喉鳞状细胞癌中阳性表达率为77.19%, 显著高于不典型增生(53.13%)和癌旁正常喉组织(26.67%), 差异具有统计学意义(χ2=21.02, P＜0.001)。SIAH2的表达与组织学分级、临床分期及淋巴结转移相关(均P＜0.05);在正常喉组织(1.25±0.04)、不典型增生(1.38±0.05)及喉鳞状细胞癌组织(1.44±0.07)中SIAH2的相对表达量逐渐升高(F=61.811, P＜0.001);SIAH2阳性与阴性患者的5年生存率分别为18.18%和58.33%(χ2=5.720, P= 0.017), SIAH2阳性与阴性患者的中位生存时间分别为25个月和60个月(P＜0.05);多因素回归分析表明高表达SIAH2是喉鳞状细胞癌患者总生存期的独立预测因子。  结论  SIAH2可能作为一个癌基因参与喉鳞状细胞癌的发生发展, 过表达SIAH2与喉鳞状细胞癌患者的不良预后有关, 提示SIAH2作为一个潜在的靶基因可能对喉鳞状细胞癌的治疗有帮助。      

S-phase kinase-associated protein 2 expression in laryngeal squamous cell carcinomas and its prognostic implications

The F-box protein S-phase kinase-associated protein 2 (Skp2) positively regulates the G1-S transition by controlling the stability of several G1 regulators, such as the cell cycle inhibitor p27kip1. However, the clinical significance of Skp2 in patients with laryngeal squamous cell carcinoma (LSCC) remains unknown. In this study, a potential distribution of Skp2 in LSCC and its clinical implications was investigated by an immunohistochemical study. Overall, Skp2 overexpression was observed in 36.7% (37 of 102) patients and was significantly associated with lymph node metastasis (p=0.002) and was inversely associated with p27kip1 expression (p=0.026). Survival analysis using the Kaplan-Meier method showed that Skp2 overexpression was significantly associated with shorter disease-free and overall survival (p=0.0051 and p=0.0002, respectively). When Skp2 expression and p27kip1 expression were combined, patients with both Skp2 overexpression and reduced expression of p27kip1 revealed poorest disease-free and overall survival as compared to the other cases (p=0.0017 and p<0.0001, respectively). Additionally, in early stage (I, II) cases, Skp2 expression was also revealed to possess a significant prognostic factor in overall survival (p=0.0234), but not in disease-free survival (p=0.2055). By multivariate analysis using the Cox proportional hazards model, tumor grade, tumor size, clinical stage and Skp2 expression were independent prognostic factors both in disease-free and overall survival. These findings indicated that Skp2 expression was closely associated with tumor progression and represented an independent marker for prognosis of LSCC.