IGF-1R expression predicts clinical outcome in patients with locally advanced oral squamous cell carcinoma

To assess the expression of IGF-1R in oral cavity squamous cell carcinoma patients, to explore its relation with clinical and pathologic prognostic factors and its role in predicting clinical outcome. One hundred and thirty-one consecutive patients suffering from oral cavity squamous cell carcinoma were included in this study from July 1989 to April 2005. Follow-up was closed in May 2010. The mean follow-up for survivors was 110.26±47.42 months. Patients were staged following the TNM classification. Patients in tumour stages I and II were referred to surgery. Patients in stages III-IV were referred to postoperative radiotherapy. Radiation therapy was administered up to a mean dose of 62.13±7.74 Gy in 1.8-2 Gy fractions. IGF-1R expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. IGF-1R was expressed in 101 patients (77.1%). IGF-1R expression was related to tumour grade (P=0.012). Tumour stage was the most important prognostic factor for survival. Low (negative and fairly) IGF-1R tumour expression was correlated to better long-term Local Disease Free Survival (P=0.016), Disease-Free Survival (P=0.029), and Survival (P=0.009) in patients achieving tumour stages III-IV. Low IGF-1R expression was related to better long-term control in patients suffering locally advanced oral carcinoma.     

CD44 expression and its relationship with MMP-9, clinicopathological factors and survival in oral squamous cell carcinoma

We investigated the expression of CD44 and MMP-9 in primary oral squamous cell carcinoma (OSCC) and evaluated their association with each other and clinicopathological factors as well as their prognostic value during long term follow up. Histological samples from 138 OSCC patients were immunohistochemically stained for the expression of CD44 and MMP-9. The staining results were compared with conventional prognostic factors and their impacts to patients' prognosis were also studied with survival analyses. Irregular staining of CD44 in tumour cells was associated with poor tumour differentiation (p=0.003), higher clinical stage (III-IV) (p=0.049), and the presence of T3-4 tumour stage (p=0.03). Strong stromal MMP-9 staining intensity was correlated with poor tumour differentiation (p=0.03). In univariate survival analysis irregular staining of CD44 in tumour cells was related to poor disease free and overall survival (p=0.001 and p<0.001, respectively). In multivariate analysis CD44 staining was a significant independent predictor for overall (p=0.03) and disease free survival (p=0.003). MMP-9 expression showed no statistical significance in survival analyses. Strong stromal staining intensity of MMP-9 correlated with irregular staining of CD44 in tumour cells, but had no prognostic significance in the present cohort. However, irregular staining of CD44 predicted more advanced disease and shortened survival of the patients.     

Activation of insulin-like growth factor 1 receptor in patients with non-small cell lung cancer

According to previous reports demonstrating the implication of insulin-like growth factor receptor (IGF-1R) signaling in non-small cell lung cancer (NSCLC), in this study, the potential prognostic values of IGF-1R expression/activation were analyzed. The expression and activation of IGF-1R were evaluated in two tissue microarray (TMA) sets from NSCLC patients (N = 352 for TMA I, and N = 353 for TMA II). Alterations in IGF-1R protein or mRNA expression in NSCLC patients were evaluated using publicly available data from The Cancer Genome Atlas (TCGA). We found that membranous and cytoplasmic IGF-1R expressions were significantly associated with squamous cell carcinoma (SCC) in both of the TMAs. Analysis of the TCGA data revealed increased mRNA levels in NSCLC patients, which was significantly associated with reductions in overall survival (OS) (median survival 26.51 vs. 47.77 months, P = 0.017) and disease-free survival (median survival 17.44 vs. 37.65 months, P = 0.045) only in NSCLC patients with adenocarcinoma (ADC). These data suggest that IGF-1R is activated in patients with NSCLC, particularly those with SCC. IGF-1R mRNA expression is a potential prognostic factor in patients with NSCLC, especially those with ADC. Further studies are warranted to investigate the prognostic value of IGF-1R in NSCLC patients.     

Expressions of insulin-like growth factor receptor-1 and insulin-like growth factor binding protein 3 in advanced non-small-cell lung cancer

BackgroundThe insulin-like growth factor (IGF) pathway plays an important role in cell proliferation, differentiation, and apoptosis, and IGF induces those effects mainly through IGF receptor-1 (IGF-1R). The activities of IGF are strictly regulated by a family of IGF binding proteins (IGFBP), especially IGFBP3, a major serum carrier protein for IGF.Patients and MethodsBetween January 2006 and February 2009, in our hospital, 191 patients were histologically diagnosed as having non–small-cell lung cancer (NSCLC), and 74 patients were treated by chemotherapy alone. We examined immunohistochemical expression of both IGF-1R and IGFBP3 in 68 patients who were definitively diagnosed as having adenocarcinoma or squamous cell carcinoma among the 74 patients.ResultsThe clinical characteristics of the included patients were as follows: median age was 68 years (range, 29-86 years); men vs. women, 40 vs. 28; stage III vs. IV, 18 vs. 50; performance status 0-1 vs. 2-4, 58 vs. 10; smoker vs. non-smoker, 44 vs. 24; and squamous cell carcinoma vs. adenocarcinoma, 13 vs. 55. Expression of IGF-1R and IGFBP3 was observed in 37 (54%) and 11 patients (16%), respectively. IGF-1R expression was detected more frequently in patients with squamous cell carcinoma (100%) than in patients with adenocarcinoma (44%) (P < .001), although IGFBP3 expression was not significantly associated with any clinical variables. Among all factors, including IGF-1R and IGFBP3 expression, IGF-1R was significantly associated with response to chemotherapy (P = .028) and performance status was significantly associated with overall survival (P < .001).ConclusionsHigh sensitivity of IGF-1R to squamous cell carcinoma (100%) in this study and another study encourages the use of IGF-1R antibody in the pathologic diagnosis between squamous cell and non-squamous cell carcinoma when using small biopsy specimens.     

High EGFR expression predicts poor prognosis in patients with squamous cell carcinoma of the oral cavity and oropharynx: a TMA-based immunohistochemical analysis

This retrospective study was designed to investigate the prognostic significance of EGFR overexpression in human oral squamous cell carcinoma on a long-term follow-up. EGFR expression was examined immunohistochemically on a tissue microarray (TMA) of paraffin embedded tissue specimens from 109 patients who underwent surgical treatment for squamous cell carcinoma of the oral cavity and oropharynx in the period between 1980 and 1997. High EGFR expression was found in 80 (73.42%) of the tumour samples. Kaplan-Meier curves showed that EGFR overexpression was significantly related to decreased overall survival (p=0.05). Multivariate analysis showed that EGFR overexpression is an independent prognostic marker in these patients (p=0.02, RR 3.6). These results confirm that EGFR overexpression is an independent prognostic marker in patients with squamous cell carcinoma of the oral cavity and oropharynx. The EGFR antigen represents an attractive target for targeted therapies with monoclonal antibodies or specific tyrosine-kinase inhibitors in these patients.     

Elevated levels of serum amyloid A indicate poor prognosis in patients with esophageal squamous cell carcinoma

ABSTRACT: BACKGROUND: Increase of Serum amyloid A (SAA) level has been observed in patients with a variety of cancers. The objective of this study was to determined whether SAA level could be used as a prognostic parameter in patients with esophageal squamous cell carcinoma (ESCC). METHODS: SAA levels were measured by rate nephelometry immunoassay in 167 healthy controls and 167 ESCC patients prior to surgical resection. Statistical associations between clinicopathological observations and SAA levels were determined using the Mann--Whitney U test. The clinical value of SAA level as a prognostic parameter was evaluated using the Cox's proportional hazards model. RESULTS: SAA levels were significantly higher in patients with ESCC compared to levels in healthy controls (13.88 [PLUS-MINUS SIGN] 15.19 mg/L vs. 2.26 [PLUS-MINUS SIGN] 1.66 mg/L, P < 0.001). Elevation of SAA levels ([GREATER-THAN OR EQUAL TO] 8.0 mg/L) was observed in 54.5% (91/167) of patients with ESCC but not in healthy controls. SAA levels were associated with tumor size (P < 0.001), histological differentiation (P = 0.015), T classification (P < 0.001), clinical stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis (P < 0.001), but not with the age and gender of the patients or tumor location. Multivariate analysis revealed that patients with an elevated level of SAA ([GREATER-THAN OR EQUAL TO] 8.0 mg/L) had significantly lower 5-year survival rate than those with non-elevated SAA (< 8.0 mg/L, log-rank P < 0.0001). CONCLUSIONS: An elevated level of preoperative SAA was found to associate with tumor progression and poor survival in patients with ESCC.     

IGF-1R和IRS-1在肺鳞癌组织中的表达及临床意义

目的 检测胰岛素样生长因子1受体(IGF-1R)和胰岛素受体底物1(IRS-1)在肺鳞癌组织中的表达,探究其在肺鳞癌发生发展中的作用及临床意义。方法 采用免疫组化法检测246例肺鳞癌组织与40例癌旁正常组织中IGF-1R、IRS-1的表达情况,并分析两者的相关性及与临床病理特征和预后的关系。结果 IGF-1R在肺鳞癌组织中的阳性表达率明显高于癌旁组织,其表达率分别为54.07%和32.5%,IRS-1在肺鳞癌组织中的阳性表达率明显低于癌旁组织,其表达率分别为38.21%和70%,各组间差异均有统计学意义(P＜0.05)。IGF-1R的表达与淋巴结转移相关(P＜0.05),IRS-1的表达与肺鳞癌组织的分化程度、淋巴结转移相关(P＜0.05)。IGF-1R阳性表达组患者的生存期明显短于IGF-1R阴性表达组患者,IRS-1阳性表达组患者的生存期明显长于IRS-1阴性表达组患者,差异有统计学意义(P＜0.001,P＜0.05)。IGF-1R与IRS-1在肺鳞癌组织中的表达呈负相关(r=-0.125,P＜0.001)。结论 IGF-1R、IRS-1都参与了肺鳞癌的发生、发展,且IGF-1R为独立预后因子。     

Clinical implications of insulin-like growth factor 1 system in early-stage cervical cancer

This study was aimed to identify the expression and the correlation of insulin-like growth factor-1 (IGF-1) system and their prognostic impacts in cervical cancer. Seventy-two patients with early-stage cervical cancer were eligible. We obtained the serum levels of total IGF-1 and IGF binding protein-3 (IGFBP-3) by enzyme-linked immunosorbent assay and the expression of IGF-1 receptor (IGF-1R) in cancerous tissue by immuno-fluorescent (IF) stains. The 5-year recurrence-free and overall survival rates were significantly lower (P=0.003 and P=0.01, respectively) among patients with high-grade expression of tissue IGF-1R, compared with those with low-grade expression. After adjustment for other factors, preoperative serum total IGF-1 or IGFBP-3 levels failed to predict cancer death and recurrence. High-grade expression of IGF-1R and elevated preoperative squamous cell carcinoma antigen level were independent predictors of both death and recurrence, and combination of both factors could further help identify the subgroup of patients at higher death risk. The IF staining indicates the colocalisation of IGF-1 and IGF-1R in the cancerous tissues, whereas the IGF-1R expression is not correlated with circulating levels of IGF-1 or IGFBP-3. In early-stage cervical cancer, IGF-1 system may have a paracrine or autocrine function and the adverse impacts on prognosis by IGF-1R overexpression are implicated.     

胰岛素样生长因子1受体在食管鳞癌组织中的表达及RNA干扰沉默其表达对EC9706细胞增殖能力的影响

目的 探讨胰岛素样生长因子1受体(IGF-1R)在食管鳞癌组织中的表达及其与患者临床特征之间的关系,以及RNA干扰沉默其表达对人食管癌EC-9706细胞体外增殖能力的影响.方法 采用免疫组化法,检测80例食管鳞癌组织和18例正常食管上皮组织中IGF-1R的表达,通过RNA干扰技术沉默EC9706细胞中IGF-1R的表达,通过绘制生长曲线、四甲基偶氮唑蓝(MTT)实验和平板克隆形成试验,观察IGF-1R对细胞体外增殖能力的影响.结果 食管鳞癌组织中IGF-1R表达的总阳性率为86.3%,强阳性率为51.3%;正常食管上皮组织中IGF-1R表达的总阳性率为61.1%,强阳性率为11.1%.食管鳞癌组织中IGF-1R表达的总阳性率和强阳性率均高于正常食管组织(P＜0.01).有淋巴结转移患者组织中IGF-1R表达的总阳性率和强阳性率均高于无淋巴结转移患者(P＜0.01).IGF-1R的表达随肿瘤组织分化程度的增高而降低,差异均有统计学意义(均P＜0.05).不同年龄组间IGF-1R表达差异无统计学意义(均P＞0.05).Ⅲ～Ⅳ期患者组织中IGF-IR表达的总阳性率和强阳性率均高于Ⅰ～Ⅱ期患者(P＜0.01).稳定干扰后的EC9706细胞IGF-1R蛋白表达下降,生长缓慢,细胞倍增时间较实验对照组和空白对照组延长.培养48 h后,稳定转染细胞抑制率为17.3%,高于实验对照组(2.7%,P＜0.01).稳定转染细胞较实验对照组和空白对照组细胞克隆形成能力减弱(P＜0.05).结论 IGF-1R在食管鳞癌组织中呈高表达,与食管鳞癌的发生、转移、分化程度和临床分期相关;RNA干扰沉默IGF-IR的表达,可以使EC9706细胞的体外增殖能力降低.

Abstract：

Objective To explore the correlation of IGF-1R expression with clinical features of esophageal squamous cell carcinoma (ESCC) and to investigate the effect of silencing IGF-1R by siRNA on the proliferation of esophageal cancer cell line EC9706 cells. Methods Immunohistochemistry was used to detect the expresion of IGF-1R in 80 specimens of ESCC and 18 specimens of normal esophageal mucosa.IGF-I R siRNA was transfected into esophageal squamous cell carcinoma EC9706 cells, and the effect of RNAi was assessed by Western blot. The proliferation of EC9706 cells was determined by drawing growth curve, MTT assay and plate colony-forming assay. Results The total and strong positive rates of IGF-1R expression were 86.3% and 51.3% in ESCC, and 61.1% and 11.1% in normal esophageal epithelium,respectively. The total and strong positive rates of IGF-1 R expression in patients with lymph node metastasis were 94.4% and 74.1%, significantly higher than 69.2% and 3.9%, respectively, in those without lymph node metastasis (P ＜ 0. 01 ). A significantly higher IGF-1 R expression was associated with lower histological grade ( P ＜ 0.05 ). The total and strong rates of IGF-1 R expression in 39 patients of stages Ⅲ and Ⅳ were 97.4% and 71.8%, significantly higher than the 75.6% and 31.7%, respectively, in 41 cases of stages Ⅰ and Ⅱ (P ＜ 0. 01 ). IGF-1 R RNAi significantly inhibited IGF-1R expression and the growth of EC9706cells. The clone formation rate of RNAi-IGF-1R transfected cells was 19.1%, significantly lower than that of 52. 3% in non-transfected cells and 49.0% in empty vector-transfected EC9706 cells ( P ＜ 0.05 ).Conclusions The overexpression of IGF-1R is colerated with lymph node metastasis, differentiation and clinical stage. Down-regulation of IGF-1R can inhibit the proliferation of esophageal cancer EC9706 cells in vitro.     

A phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin for metastatic squamous cell lung carcinoma.

BACKGROUND. In an effort to confirm the efficacy of mitomycin C against metastatic squamous cell lung carcinoma and to compare the efficacy of single-agent therapy with a combination containing cisplatin, the authors conducted a randomized Phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin (MVP). METHODS. All patients had advanced squamous cell lung carcinoma, and survival was the primary end point. There were 133 eligible patients who received either mitomycin C alone (n = 64) or MVP (n = 69). The two groups were similar with respect to performance score, disease status, age, sex, and stage. RESULTS. The major objective response rates were 30% (95% confidence interval [CI], 18-41%) and 43% (95% CI, 32-55%) for mitomycin C alone and MVP, respectively (P = 0.1). The median time to progression was 83 days for mitomycin C alone, compared with 119 days for MVP (P = 0.026). The median survival time was 114 days for mitomycin C and 163 days for MVP (P = 0.09). The 1-year survival rates were equivalent. Myelosuppression was the major toxicity, and there were significantly greater leukocyte nadirs with MVP therapy (P < 0.001). CONCLUSION. Mitomycin C has antitumor activity against squamous cell lung carcinoma when used alone or in combination with MVP. The regimen containing cisplatin had marginally increased activity that did not translate into a clinically significant survival advantage.     

Reduced expression of hyaluronan is a strong indicator of poor survival in oral squamous cell carcinoma

Several malignant tumours accumulate hyaluronan (HA), a matrix component suggested to promote cancer cell growth and migration. The expression and prognostic value of HA was analysed in a cohort of 151 oral squamous cell carcinoma (SCC) patients with adequate archival tumour material and follow-up data. The tumour samples were stained using a biotinylated HA-specific probe. Normal squamous epithelium showed a strong and homogeneously distributed staining for HA. The most superficial layers were HA-negative. In moderate (n=11) and high grade (n=16) dysplasias an irregular HA staining was observed around invasive cancer. Malignant transformation in oral squamous cell epithelium changed the staining toward irregular with focal reduction of HA. The well (n=92) or moderately differentiated (n=47) carcinomas had a strong HA staining intensity. In poorly differentiated tumours (n=12) the HA staining was weaker and mainly intracellular. The stromal tissue showed usually moderate (n=69) or strong (n=67) HA staining intensity with no statistically significant correlation with the degree of tumour differentiation. At the end of the follow-up (median 52 months) 66 (43%) patients had died because of an oral SCC. A significant difference in overall survival (OS) and disease free survival (DFS) (P=0.0002 and 0.0020, respectively) was noticed between the patients with the different epithelial staining patterns for HA. The reduction of HA staining was associated with poor survival. In Cox's multivariate analysis HA staining was a significant independent predictor of OS (P=0.011) and DFS (P=0.013). These results suggest that HA is a prognostic marker in oral squamous cell carcinoma.     

Carcinoma of the nasopharynx: results of radiation treatment and some prognostic factors

Seventy-four patients treated for squamous cell carcinoma (SCC) of the nasopharynx were evaluated for the 5-year survival rate. The influence of stage, age, histological differentiation, total tumour dose and irradiation treatment technique (continuous vs. split-course) upon the survival was evaluated in 64 patients (palliations and histologically unclassified SCC were excluded). The 5-year survival rate in the whole group was 28/74 (38%), and in the group without palliations and unclassified SCC 26/64 (41%). The 5-year survival of patients with T1 carcinoma was better (8/9 = 89%) than of patients with T2 (4/14 = 29%), T3 (7/17 = 41%) and T4 (7/24 = 29%) carcinoma. In the group of 55 patients with T2, T3 and T4 carcinoma, those up to 50 years old had better survival (11/21 = 52%) than patients older than 50 years (7/34 = 21%) (p less than 0.01), patients treated with the tumour dose greater than 65 Gy had better survival (16/38 = 42%) than those treated with 50-65 Gy (2/17 = 12%) (p less than 0.05), and patients older than 50 years, with poorly differentiated carcinoma had better survival (7/20 = 35%) than those of the same age, with well-differentiated carcinoma (0/14 = 0%) (p less than 0.005). The split-course irradiation technique did not improved the 5-year survival rate, although on average the total tumour dose in this type of treatment was for 7.9 Gy higher than in the continuous irradiation.     

Prognostic Implications of Tumoral Expression of Insulin Like Growth Factors 1 and 2 in Patients With Non–Small-Cell Lung Cancer

IntroductionThe currently available systemic therapies for non–small-cell lung cancer (NSCLC) have limited efficacy. Previous studies indicated an association of elevated insulinlike growth factor (IGF)-1 receptor (IGF-1R) and insulin receptor expression levels with poor survival in patients with NSCLC. To better understand the molecular biomarkers involved in the IGF signaling pathway in NSCLC, the expression levels of IGF-1 and IGF-2 are characterized and evaluated for their association with IGF-1R and phosphorylated IGF-1R (pIGF-1R) expression in NSCLC.Materials and MethodsA total of 352 patients who underwent NSCLC resection with curative intent were studied. The expression patterns of the IGF-1, IGF-2, IGF-1R, and pIGF-1R proteins were assessed immunohistochemically using tissue microarrays.ResultsThe IGF-1 expression was higher in patients with adenocarcinoma (ADC) than in those with squamous cell carcinoma (SCC), whereas the IGF-2 score was higher in patients with SCC than those with ADC. Likewise, the IGF-1 score was higher in patients with mutated epidermal growth factor receptor (mtEGFR) than in those with wild type EGFR (wtEGFR), whereas the IGF-2 score was higher in patients with wtEGFR than in those with mtEGFR. Patients with low levels of IGF-1 expression had longer overall survival (OS) than those with high IGF-1 expression, and subgroup analyses found a significant difference in OS only in patients with ADC.ConclusionThe overexpression of IGF-1 predicts poor survival among patients with NSCLC, especially those with ADC. These results might serve as a future guide for clinical trials involving IGF-1R-targeting agents.     

Responders benefit from neoadjuvant radiochemotherapy in esophageal squamous cell carcinoma: results of a prospective phase-II trial.

BACKGROUND: We present the results of a prospective phase-II-study of neoadjuvant combined radiochemotherapy followed by surgical resection in patients with histological proven locally advanced squamous cell carcinoma of the esophagus located at or above the level of the tracheal bifurcation. METHODOLOGY: Between February 1995 and March 2000 a total of 76 patients with esophageal squamous cell carcinoma (uT3/4N0/+-categories) received simultaneous combined neoadjuvant radiochemotherapy consisting of a continuous intravenous infusion of 5-fluorouracil (300 mg/m2/day) 7 day per week concurrently with conventional fractioned external beam radiation therapy (2 Gy/day), five fractions per week up to a total dose of 30 Gy. RESULTS: Radiochemotherapy related acute severe toxicity rate (CTC-grade-III) occurred in 34 patients, two patients died. Sixty-four patients underwent surgery with a complete resection in 48 patients. Three patients died during a 90-day post-operative course. The histopathological workup revealed no viable residual tumour cells in eight patients (ypCR) and according to the modified criteria of Mandard in 26 patients a histopathological response. Twenty-two of these patients underwent a R0-resection. The median follow-up time was 5.4 years with an overall median survival time of 20.6 months. The median survival in the 26 responders was 32.3 months versus 19.5 months in 38 non-responders (p=0.03). CONCLUSIONS: Patients with locally advanced squamous cell carcinoma of the esophagus, who respond to preoperative neoadjuvant combined radiochemotherapy, seem to have more benefit from subsequent resection than non-responding patients.     

Prognostic significance of nm23-H1 expression in oral squamous cell carcinoma

Recent studies indicated nm23-H1 played a role in cancer progression. Therefore, we investigated clinical significance of nm23-H1 expression in oral squamous cell carcinoma (OSCC). In total, 86 OSCC specimens were immunohistochemically stained with nm23-H1-specific monoclonal antibodies. Immunohistochemical staining of nm23-H1 was confirmed by immunoblotting. The relations between nm23-H1 expression and clinicopathologic variables were evaluated by chi(2) analysis. As increased size of primary tumour could escalate metastatic potential and the data of patients at the late T stage might confound statistical analyses, we thus paid special attention to 54 patients at the early T stage of OSCC. Statistical difference of survival was compared by a log-rank test. Immunohistochemically, nm23-H1 expression was detected in 48.8% (42 out of 86) of tumorous specimens. It positively correlated with larger primary tumour size (P=0.03) and inversely with cigarette-smoking habit (P=0.042). In patients at the early T stage, decreased nm23 expression was associated with increased incidence of lymph node metastasis (P=0.004) and indicated poor survival (P=0.014). Tumour nm23-H1 expression is a prognostic factor for predicting better survival in OSCC patients at the early T stage, which may reflect antimetastatic potential of nm23. Therefore, modulation of nm23-H1 expression in cancer cells can provide a novel possibility of improving therapeutic strategy at this stage. In addition, our results further indicated cigarette smoking could aggravate the extent of nm23-H1 expression and possibly disease progression of OSCC patients.     

p53 Expression Helps Identify High Risk Oral Tongue Premalignant Lesions and Correlates with Patterns of Invasive Tumour Front and Tumour Depth in Oral Tongue Squamous Cell Carcinoma Cases

Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cancer subtype with a maximum propensity for regional spread. Our objective was to study if p53 expression might have any correlation with aggressive patterns of invasion within oral tongue cancers as well as with the histologically identified degree of oral tongue dysplasia. p53 immunoexpression was studied using immunohistochemistry in early staged OTSCCs (n=155), oral tongue dysplasias, (n=29) and oral tongue normal specimens (n=10) and evaluated for correlations with histological and clinicopathological parameters. Our study (n=194) showed a pattern of p53 expression increasing with different grades of tongue dysplasia to different grades of invasive OTSCC (p=0.000). Among the OTSCC tumours, positive p53 expression was seen in 43.2% (67/155) and a higher p53 labelling index was significantly associated with increased Bryne’s grade of the tumour invasive front (p=0.039) and increased tumour depth (p=0.018). Among the OTSCC patients with tobacco habits, (n=91), a higher p53 labelling index was significantly associated with increased risk of local recurrence (p=0.025) and with lymphovascular space involvement (p=0.014). Evaluation of p53 through varying degrees of dysplasia to oral tongue cancer indicates that p53 expression is linked to aggressive features of oral tongue cancers and tongue precancers entailing a closer monitoring in positive cases. Among the OTSCCs, p53 expression is associated with tumour aggressiveness correlating with increased grading of invasive tumour front and tumour depth.     

Reduced E-cadherin expression is an indicator of unfavourable prognosis in oral squamous cell carcinoma

The aim was to evaluate E-cadherin expression in oral squamous cell carcinoma, and its possible relationships with tumour histology and with clinical course and survival. Surgical biopsies from 47 cases of oral squamous cell carcinoma were analysed for expression of E-cadherin using immunohistochemistry. Statistical analyses were performed to identify possible associations with tumour clinic-histological features and with clinical course and survival. Weak or absent E-cadherin expression was associated with a more invasive histological pattern and with metastasis to the cervical lymph nodes. Uni- and multivariate analyses indicated that weak or undetectable E-cadherin expression is an indicator of shorter disease-free period and shorter survival time. Reduced E-cadherin expression in oral squamous cell carcinoma is associated with more aggressive tumour behaviour and worse prognosis.     

PLCE1在口腔鳞状细胞癌中的表达及其临床意义

目的:探讨磷脂酶Cε1（phospholipase C epsilon－1,PLCE1)在口腔鳞状细胞癌(OSCC)组织中的表达及其与临床病理特征和患者预后的关系。方法:应用免疫组织化学方法检测PLCE1在83例OSCC组织和20例正常口腔黏膜组织中的表达,并分析 PLCE1表达与OSCC临床病理特征的关系;采用Kaplan-Meier法进行生存分析,Cox 风险比例回归模型分析影响OSCC患者预后的独立因素。结果:PLCE1在OSCC组织与口腔正常黏膜组织中高表达率分别为53.01%和15.00%,差异有统计学意义（P=0.002）。PLCE1的表达与患者年龄、性别、吸烟无相关性,而与肿瘤分化程度、T分期、临床分期、N分期有密切关系。单变量分析显示临床分期、PLCE1、T分期、N分期是影响OSCC预后的因素,双变量分析显示PLCE1是其独立预后因素。结论:PLCE1过表达与OSCC的发生、发展密切相关,可作为判断OSCC恶性程度和不良预后的参考指标。     

Clinicopathologic significance of bcl-2 expression in the surgical treatment of oral tongue carcinoma.

AIM: There is still controversy on the incidence of positive expression of bcl-2 and its prognostic significance for oral tongue carcinoma patients who are treated by surgery. The present study aims at resolving the controversy on the clinicopathologic significance of bcl-2 in a well selected group of patients who satisfy the recruitment criteria: (1) oral tongue carcinoma, (2) squamous cell carcinoma, (3) primary surgical treatment.METHOD: Bcl-2 expression was studied by immunohistochemistry on glossectomy specimens of 73 patients. The expression of bcl-2 was correlated with clinicopathologic data.RESULTS: Of the 73 tumours, 11% had positive expression of bcl-2. Bcl-2 expression was not significantly correlated with tumour grade, stage, nodal metastasis and survival.CONCLUSION: Bcl-2 expression played a minor role in oral tongue carcinoma. It had no significant correlation with tumour grade, stage and nodal metastasis. It also had no prognostic value on survival for patients who were treated by primary surgery.