Expression of cancer stem cell markers ALDH1 and Bmi1 in oral erythroplakia and the risk of oral cancer

J Oral Pathol Med (2013) 42 : 148–153 Background: Oral erythroplakia (OE) is a notoriously aggressive oral pre‐malignant lesion with a high tendency to oral cancer development, but its biological behavior is largely unknown. The objective of this study was to determine the expression of cancer stem cell markers ALDH1 and Bmi1 in OE and their correlation with malignant transformation of OE. Methods: In a retrospective case–control study, expression patterns of ALDH1 and Bmi1 were determined using immunohistochemistry in samples from 34 patients with OE, including patients with untransformed lesions (n = 17) and patients with malignant transformed lesions (n = 17). Results: ALDH1 and Bmi1 expression was observed in 19 (55.9%) and 20 (58.8%) of 34 patients with OE, respectively. Multivariate analysis revealed that ALDH1 expression was significantly associated with increased risk of transformation (P < 0.05), but Bmi1 expression was not a significant marker (P > 0.05). Notably, the coexpression of both ALDH1 and Bmi1 was a strong indicator associated with 8.56‐fold (95% confidence interval [CI], 1.74–42.17; P < 0.01) for malignant transformation. Point prevalence analysis revealed that 78.6% (95% CI, 54.0–100) of the patient with coexpression of both ALDH1 and Bmi1 developed oral cancer. Conclusion: Our data indicated that the expression patterns of ALDH1 and Bmi1 in OE were associated with malignant transformation, suggesting that they may be valuable predictors for evaluating the risk of oral cancer.     

Prognostic significance of matrix metalloproteinase-2, -8, -9, and -13 in oral tongue cancer

J Oral Pathol Med (2012) 41 : 394–399 Background: Oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. Mechanisms of this disease progression are not fully known. We aimed at finding new predictive markers for diagnosis and disease monitoring. Methods: Seventy‐three consecutive T1N0M0 and T2N0M0 OTSCC patients treated at Helsinki University Central Hospital, Helsinki, Finland, in 1992–2002 were included. Tissue array blocks were prepared from primary tumors and immunostained. Immunoexpression of matrix metalloproteinase (MMP)‐2, ‐8, ‐9, and ‐13 was compared with patient characteristics and outcome. Results: Nuclear expression of MMP‐13, but not cytoplasmic expression of MMP‐2, ‐8, and ‐9, was associated with invasion depth (P = 0.017) and tumor size (P = 0.008). Furthermore, high nuclear MMP‐13 expression was predictive of poor outcome (P = 0.042). Conclusion: Our results suggest that especially MMP‐13 may be regarded as a prognostic biomarker in OTSCC.     

CYP2E1RsaI/PstI位点多态性与口腔癌易感性的Meta分析

目的:运用Meta的分析方法研究CYP2E1 Rsa I/Pst I多态性与口腔癌易感性的相互关系。方法:检索VIP,CNKI和PubMed数据库中有关CYP2E1 Rsa I/Pst I多态性与口腔癌易感性关联研究的文献,以OR值和95%的可信区间为效应指标,应用Rev Man 4.2软件进行Meta分析,并使用STATA 11.0软件对发表偏倚进行检验。结果:纳入12个病例对照研究,共计1259例口腔癌患者和2262例正常对照,Meta分析结果显示,总人群中c1/c2 vs.c1/c1(OR=1.30,95%CI=1.04～1.62),c1/c2+c2/c2 vs.c1/c1(OR=1.32,95%CI=1.07～1.64)。结论:CYP2E1突变基因型c2可能会增加口腔癌发生的风险。     

UHRF1在口腔黏膜鳞癌中的表达及其对临床预后的价值研究

目的 分析泛素样含PHD和环指域1(ubiquitin like with PHD and ring finger domains 1,UHRF1)在口腔黏膜鳞状细胞癌中的表达及其临床意义。方法 收集2008—2016年间,于中国科学技术大学附属第一医院口腔颌面外科接受手术治疗的原发性口腔鳞癌患者,利用免疫荧光染色评估患者的肿瘤组织、癌旁正常组织及侵袭前沿中的UHRF1表达,了解其表达差异性。以免疫反应强度分布指数(immunoreactivity intensity distribution index, IRIDI)值4分为界限,将患者分为UHRF1高表达组和低表达组,分析UHRF1表达水平与患者临床病理特征之间的关系,利用Kaplan-Meier法对肿瘤组织中UHRF1表达水平与患者生存率的相关性进行分析,运用Cox风险模型对影响口腔癌患者生存率的相关危险因素进行分析。结果 与肿瘤侵袭前沿、癌旁正常组织相比,UHRF1在口腔鳞癌肿瘤组织中高表达(P<0.01)。口腔鳞癌组织中UHRF1的表达水平与患者性别、肿瘤大小、浸润深度相关(P<0.05)。UHRF1低表达组和高...     

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自噬是细胞程序性死亡的一种方式,人类多种肿瘤存在自噬异常。自噬过程受自噬相关基因调控,Beclin1是目前惟一被证实的哺乳动物自噬基因,是自噬的直接执行者,通过诱导自噬、促进凋亡抑制肿瘤进程。本文就Beclin1与肿瘤发生、发展的关系进行综述,并对口腔癌自噬研究做一简要介绍。     

口腔癌患者术后吞咽障碍评价与其早期预后的相关性研究

目的 通过对口腔癌患者术后吞咽障碍的评价,观察其与口腔癌患者早期吞咽障碍预后的相关性.方法 选取2016年9月至2019年9月于辽宁中医药大学附属医院确诊并手术治疗的口腔癌患者124例,经口腔修复后进行洼田饮水试验评估及电视X线透视吞咽功能(VFSS)检查,比较两种方法评价吞咽障碍效果.根据成功随访3个月的95例患者是...     

Prognostic and predictive factors in oral cancer: the role of the invasive tumour front

Most decisions for cancer patients are now made on the basis of prognostic and predictive factors. However, due to the limited prognostic value of conventional tumour/nodal/ metastasis staging and histopathological grading in oral cancer, a large group of patients are still over- or under-treated with significant personal and socioeconomical impact. Recent work indicates that morphological and functional characteristics of the invasive tumour front underlie the biological aggressiveness of oral cancer. Incorporation of these concepts into a prognostic system will better reflect the biologic diversity of oral cancer and more accurately predict clinical outcomes and responses to particular types of adjuvant therapy.     

The potential of CD44 as a diagnostic and prognostic tool in oral cancer

The CD44 family of molecules exists as a wide range of isoforms ubiquitously expressed on the surface of mammalian cells. The variation in patterns of CD44 expression on cancer cells has been widely studied in relation to their behaviour, and further interest has recently arisen in CD44 as a marker of the subfraction tumour cells acting as cancer stem cells in several types of tumours. This review focuses on the patterns of CD44 expression on the stem cell fraction of oral squamous cell carcinoma and on the relationship of detectably different patterns of CD44 expression to the behaviour of tumours.     

The prognostic significance of histological features in oral squamous cell carcinoma

Background:  Different factors predict nodal metastasis, recurrence and survival in oral cancer. The aim was to assess the prognostic value of histological features related to the primary tumour.
Methods:  A total of 144 patients surgically treated at Odense University Hospital for oral cancer between 1999 and 2004 were included in the study. Postoperative radiation therapy was given in case of close and involved margins or high TNM stages (UICC 1997). Median follow-up time was 38 months. All surgical resections were reviewed and 22 histological characteristics were assessed.
Results:  The predominant sites were floor of mouth (FOM, 39%) and lateral tongue (35%). Fifty-nine per cent had UICC97 stage I–II disease. Five-year cause-specific survival was observed in 65%. Nodal involvement at diagnosis was observed in 36% which was significantly related to grade, neural and vascular invasion; surgical margins and increasing tumour depth. A cut-off value of 2 mm (4 mm for FOM) separated patients without and with nodal metastasis at the time of diagnosis. However, on multivariate analysis, neck disease was only associated with tumour depth and grade. Cox analysis of local recurrence in the oral cavity over time showed that tumour diameter and surgical margins were significant predictors while cause-specific survival was related to diameter, depth of invasion, surgical margins and extracapsular spread (ECS).
Conclusions:  Tumour depth and grade were strong prognostic factors for nodal metastasis, independently of other histological features. Tumour diameter and margins independently predict local recurrences in the oral cavity as well as cause-specific survival. Nodal involvement and ECS were associated with adverse prognosis.     

Expression of hypoxia-inducible factor-1α is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan

Background:  Overexpression of hypoxia-inducible factor-1α (HIF-1α) has been found to be significantly associated with the tumor invasion, lymph node metastasis, clinical stage, and prognosis of a variety of human cancers.
Methods:  This study examined the expression of HIF-1α in 57 specimens of oral squamous cell carcinoma (OSCC), 41 specimens of oral epithelial dysplasia (OED, 12 mild, 17 moderate, and 12 severe OED cases), and 14 specimens of normal oral mucosa (NOM) by immunohistochemistry.
Results:  We found that the mean nuclear HIF-1α labeling indices (LIs) increased significantly from NOM (9 ± 6%) through mild OED (25 ± 18%), moderate OED (41 ± 27%), and severe OED (42 ± 22%) to OSCC samples (55 ± 23%, P  < 0.001). A significant correlation was found between the higher mean nuclear HIF-1α LI and OSCCs with larger tumor size ( P  < 0.001), regional lymph node metastasis ( P  < 0.001), or more advanced clinical stages ( P  < 0.001). Only larger tumor size ( P  = 0.002) and nuclear HIF-1α LI ≥ 60% ( P  = 0.048) were identified as independent unfavorable prognosis factor by multivariate analyses with Cox regression model. Kaplan–Meier curve showed that OSCC patients with a nuclear HIF-1α LI ≥ 60% had a significantly poorer cumulative survival than those with a nuclear HIF-1α LI < 60% (log-rank test, P  = 0.022).
Conclusions:  We conclude that the expression of HIF-1α is an early event in oral carcinogenesis. The nuclear HIF-1α LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.     

Lycopene: features and potential significance in the oral cancer and precancerous lesions

J Oral Pathol Med (2010) 40 : 361–368 Data from epidemiological studies have indicated that diets rich in fruits and vegetables are likely to benefit many aspects of the prevention of oral malignancy. Lycopene is a red‐coloured carotenoid predominantly accumulated in tomatoes as well as other fruits and vegetables. It has been claimed to alleviate chronic diseases such as cancers and cardiovascular disease. Hence, the aim of this review is to summarize the features and its potential significance of lycopene in the development, prevention and treatment of oral premalignant lesions and oral cancer. Studies showed that lycopene might have beneficial effects in the management of some premalignant lesions in the oral cavity including oral submucous fibrosis and oral leukoplakia and may be an adjunct in the prevention and therapy of oral cancer. However, more mechanistic studies and randomized controlled trials of large sample size are necessary to further confirm these effects and to eventually make lycopene to be used in the community prevention and clinically routine management of these diseases.     

PD1 expression and correlation with its ligands in oral cancer specimens and peripheral blood

ObjectivesThis study analyzed the expression of the PD1 receptor in tumor tissue and peripheral blood of oral squamous cell carcinoma (OSCC) patients, and correlated it with the PD1 ligands PD-L1 and PD-L2. The currently low response rates of checkpoint inhibitor treatment in OSCC could be increased by a better understanding of immune checkpoint biology. Despite evidence in the literature for upregulation of PD1 checkpoint ligands in OSCC tissue, there has been no correlation analysis of the PD1 receptor with its ligands in tissue specimens and peripheral blood of OSCC patients.Materials and methodsAn RT-qPCR analysis of PD1 mRNA expression was performed in oral cancer specimens, healthy mucosa, and corresponding blood samples. A cut-off point (COP) was determined and a chi-square (χ²) test was carried out. PD1 expression was correlated with previously reported PD-L1 and PD-L2 expression values using the Spearman test.ResultsTissue and blood specimens of 48 OSCC patients and 26 healthy individuals were analyzed. PD1 expression in OSCC specimens was significantly increased (p = 0.006) compared with healthy oral mucosa. PD1 overexpression in tissue samples showed a significant association with the presence of malignancy (p = 0.006). PD1 expression in tissue samples showed a significant positive correlation (p < 0.001) with the ligands PD-L1 and PD-L2. In contrast, there was no correlation between PD1 and its ligands in blood samples. However, there was a significant positive correlation (p < 0.001) between the ligands PD-L1 and PD-L2, both in tissue and blood samples.ConclusionsIncreased PD1 expression might be a manifestation of T-cell exhaustion in OSCC specimens, leading to immune tolerance. PD-L1/PD-L2-PD1 interaction may be a major mediator of local immunosuppression in OSCC, requiring advanced multimodal treatment protocols.