KiSS‐1 expression in oral squamous cell carcinoma and its prognostic significance

Downregulated expression of KiSS‐1 has been correlated with tumor progression, metastasis, and patient prognosis in various human malignancies. However, there is no information regarding the expression of KiSS‐1 in oral squamous cell carcinoma (OSCC). Our aims were to examine KiSS‐1 expression in OSCC tissue samples and cell lines and to determine its prognostic significance. KiSS‐1 expression was significantly lower in lymph node (LN) metastases than in primary tumor tissues. Five of six OSCC cell lines showed absence or relatively low expression of KiSS‐1. Correlations between KiSS‐1 expression and clinicopathological parameters were statistically assessed. There were significant correlations between KiSS‐1 expression and LN metastasis (p = 0.007), TNM stage (p = 0.024), and local recurrence (p = 0.012). In the Kaplan–Meier survival analysis, negative KiSS‐1 expression significantly correlated with poorer overall survival (OS) and disease‐free survival (DFS) (p = 0.000 and 0.000, respectively). Multivariate analysis using Cox regression modeling revealed that KiSS‐1 expression was an independent prognostic factor for both OS and DFS (p = 0.001 and 0.000, respectively). Our findings suggested that KiSS‐1 downregulation may play a role in tumor progression and metastasis of OSCC and may be a reliable biomarker for predicting clinical outcome in OSCC.     

新疆地区口腔鳞状细胞癌中PLCE1蛋白的表达及临床意义

目的探讨PLCE1蛋白在新疆地区口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达及预后价值。方法采用免疫组化EnVision两步法检测124例OSCC及63例癌旁正常组织中PLCE1蛋白的表达,分析其表达与OSCC临床病理特征及预后的关系。结果OSCC及癌旁组织中PLCE1蛋白高表达率分别为41.9%(52/124)和0(0/63),差异有统计学意义(P<0.0001)。PLCE1诊断OSCC的ROC曲线下面积(AUC)为0.954(敏感度83.9%,特异性95.2%)。Kaplan-Meier及Cox单因素分析显示,PLCE1高表达(P=0.004、P=0.006)和T分期(P=0.002、P=0.004)是影响患者不良预后的危险因素。Cox多因素分析结果显示,PLCE1高表达(P=0.008)和T分期(P=0.005)是患者预后的独立因素。结论PLCE1蛋白在新疆地区OSCC组织中高表达,且与患者不良预后相关,可作为肿瘤患者不良预后的新型生物标志物。     

The behaviour of human oral squamous cell carcinoma in cell culture.

This study examined the initial behaviour of 48 human oral squamous cell carcinomas (SCC) in cell culture. The early outcome of these cultures (contamination, absence of cell growth, epithelial cell senescence/fibroblast overgrowth, extended keratinocyte growth) did not reflect the clinical characteristics of the tumours of origin. Four new human oral SCC cell lines were characterized more extensively. Each cell line was immortal, 3T3-independent, and expressed low degrees of anchorage independence (CFE less than 4 per cent). Two of the four cell lines were tumorigenic in athymic mice. All of the cell lines expressed keratin intermediate filaments and two showed weak co-expression of vimentin. A wide range of keratins were expressed by the tumour xenografts; cornified keratins (K1, K10) were only expressed in the absence of K19 and vimentin, and vice versa. The nuclear:cytoplasmic ratio and the degree of serum independence correlated with each other and with the STNMP clinical grading of the tumours of origin.     

Prognostic value of the PIK3CA,AKT, and PTEN mutations in oral squamous cell carcinoma: literature review

Over 260,000 (2013) new oral squamous cell carcinoma (OSCC) cases are reported annually worldwide. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new molecular markers may be of use in prevention, prognosis, and choice of an appropriate therapy. The intracellular molecular signalling pathway of phosphatidyl-inositol-3-kinase is involved in the process of cell growth, differentiation, migration, and survival. The main components of this pathway: PIK3CA (phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit α), PTEN (phosphatase and tensin homologue deleted on chromosome 10), and AKT (serine-threonine kinase) are potential objects of research when introducing new therapeutic agents. The aim of this paper is to evaluate the PIK3CA, PTEN, and AKT gene mutations as prognostic factors in OSCC and to describe their role in aggressive disease progression. This is crucial for oral cancer biology understanding and for indicating which direction new clinical treatments should take.     

Adenoid squamous cell carcinoma of the larynx: an uncommon histological variant of squamous cell carcinoma

Adenoid squamous cell carcinoma (ASCC) or acantholytic squamous cell carcinoma is a well-recognized variant of squamous cell carcinoma. ASCC commonly occurs in the sun-exposed areas of the skin and has only rarely been observed in mucosal sites. We report a case of ASCC in the larynx of a 75-year-old man with a history of odynophagia and dysphonia of 3 months' duration that presented as an exophytic lesion on the right vocal cord. Biopsy was performed and the histological diagnosis was squamous cell carcinoma. Treatment consisted of total laryngectomy and radical neck dissection. Microscopically, the tumor showed a prominent alveolar pattern with cystic degeneration of the neoplastic epithelium and formation of pseudoglandular structures. In the lumina there were acantholytic cells. Transition areas from conventional squamous cell carcinoma to adenoid pattern were found. To the best of our knowledge this is only the third case of ASCC reported in the larynx. We reviewed the nine mucosal ASCCs of the upper aerodigestive tract reported. The assertion that these tumors are associated with an aggressive behavior and poor prognosis cannot be estimated in this review as the number of cases is small and the tumors are located in different places.     

Prognostic role of CD11b+ myeloid-derived suppressor cells in oral squamous cell carcinoma

IntroductionMyeloid-derived suppressor cells (MDSCs) are critically involved in cancer immune suppression and MDSC density has been recognized as a robust prognostic biomarker. Here, we sought to characterize the densities and locations of CD11b⁺ MDSCs in primary oral squamous cell carcinoma (OSCC) and determine their prognostic significance.Material and methodsA total of 144 eligible OSCC samples from a tertiary referral oral cancer center were retrospectively collected. Intensities of CD11b⁺ MDSCs at the tumor center (CT) and invasive margin (IM) in OSCC samples were detected by immunohistochemistry and automatically quantified using Image J software. The optimal cutoff values for CD11b CT and CD11b IM were determined by X-tile based on overall survival. The associations between CD11b⁺ MDSCs and clinicopathological parameters were assessed by the χ² test. The prognostic value of CD11b⁺ MDSCs was evaluated by Kaplan-Meier plots, Cox regression analyses and receiver operating characteristics curves.ResultsHigh density of CD11b⁺ MDSCs at CT or IM was significantly associated with inferior overall and disease-free survival (Kaplan-Meir, p < 0.05, log-rank test). CD11b CT and CD11b IM were identified as independent prognostic predictors for patient survival. The prediction accuracy and specificity of CD11b CT and CD11b IM were superior to other prognostic parameters.ConclusionsOur data indicated that increased densities of CD11b⁺ MDSCs in CT and IM regions were significantly associated with poor prognoses, which might be novel prognostic factors for OSCC.     

Prognostic implications of epidermal growth factor receptor immunoreactivity in squamous cell carcinoma of the oral mucosa

To evaluate the clinical significance of the expression of epidermal growth factor receptor (EGFr) in oral squamous cell carcinoma (SCC), 100 formalin-fixed, paraffin-embedded cases of this tumour and ten samples of normal oral mucosa were immunostained with a monoclonal anti-EGFr antibody using an immunoalkaline phosphatase (APAAP) technique. EGFr immunoreactivity was detected in 36 of 100 tumours and in all samples of normal mucosa. Tumour cells demonstrated distinct membrane staining in 14 cases and predominantly cytoplasmic staining in 22 additional cases. EGFr was exclusively localized on the cell membrane of normal epithelial cells. Kaplan–Meyer survival curves and Cox proportional hazard regression models were used to assess overall survival and disease-free survival. A significant positive correlation was shown between EGFr membranous immunoreactivity and prolonged survival, in both univariate and multivariate analyses. Accordingly, patients with oral SCC showing down-regulated expression of membranous EGFr, who are more likely to suffer recurrence and death, should be strictly followed up and possibly treated with more aggressive therapeutic regimens. © 1998 John Wiley & Sons, Ltd.     

Immunohistochemical study of desmosomes in oral squamous cell carcinoma: correlation with cytokeratin and E-cadherin staining,and with tumour behaviour

Reduction or loss of the intercellular junctions known as desmosomes may contribute to the invasive and metastatic behaviour of various carcinomas. Previous studies have shown that metastasis of oral squamous cell carcinomas of the head and neck correlates with a reduction in immunohistochemical staining for desmoplakin and desmoglein at the invasion front. The primary aim of the present study was to extend these observations to include a third component of desmosomes, the glycoprotein desmocollin. An additional aim was to determine whether the differentiation status of tumours is reflected in their staining for cytokeratins 1, 13, and 19, and, if so, whether these parameters correlate with desmosomal staining and/or metastasis. The study included 54 primary tumours of which 28 showed lymph node metastases. The results of this investigation show that tumours can be divided into three groups according to whether they have lost staining for no, one or more than one desmosomal component. A statistically significant correlation was found between the number of desmosomal components lost and metastasis. Tumours could also be divided into five groups according to their staining for different combinations of cytokeratins. Furthermore, differentiation status as indicated both histologically and by cytokeratin staining correlated with reduced desmosomal staining and metastasis. Tumours were also examined for intensity of staining for the adhesion molecule E-cadherin. Reduction in E-cadherin staining was correlated with mode of invasion and with reduction in desmosomal staining, but not with poor differentiation as indicated by cytokeratin staining. The results of this extensive study reinforce the view that adhesive junctions and adhesion molecules contribute to the suppression of tumour invasion and metastasis. © 1998 John Wiley & Sons, Ltd.     

Association of nuclear annexin A1 with prognosis of patients with esophageal squamous cell carcinoma

Although recent progress has been made in the diagnosis and treatment of cancer, the prognosis of esophageal squamous cell carcinoma (ESCC) remains poor. The identification of biomarkers for ESCC prognosis is important for treatment decisions. The aim of this study was to evaluate the relationship between the expressions of Annexin A1 (ANXA1), three prime repair exonuclease 1 (TREX1) and apurinic/apyrimidinic endonuclease-1 (APE1) and clinical outcome of patients with ESCC. The expressions of ANXA1, TREX1 and APE1 in 93 pairs of ESCC and paracancerous tissues were tested using immunohistochemistry. ANX1, TREX1 and APE1 were dysregulated in ESCC. Nuclear expressions of ANXA1 and APE1 were significantly associated with pathologic type (P = 0.004 and 0.040, respectively). Patients with low expression of nuclear ANXA1 had a better prognosis than those with high expression of nuclear ANXA1 (HR = 0. 448, 95% CI 0.236-0.849, P = 0.014), especially for those with histologic grade 1 and 2 (HR = 0.303, 95% CI: 0.155-0.593, P < 0.001). In conclusion, nuclear ANXA1 may be potentially used as a prognostic biomarker for ESCC.     

Primary adenoid squamous cell carcinoma of the oral cavity

Adenoid squamous cell carcinoma (ASCC) is an uncommon but well-recognized variant of squamous cell carcinoma that was first described by Lever in 1947. ASCC has been reported to originate in the sun-exposed skin of the head and neck and in other sites. An additional case of ASCC is reported here. The patient was a 64-year-old Japanese woman who requested examination of a reddish lesion on the left floor of the mouth. The biopsy material was diagnosed as squamous cell carcinoma. Clinical examination showed a well-circumscribed, 20 x 10 mm-sized lesion, which was categorized as cT2cN0cm 0. Tumor resection was therefore performed. Histologically, most parts of the lesion were conventional squamous cell carcinoma in situ, but the invasive part consisted of ASCC with gland-like or reticular appearance. The latter part was negative for mucin staining. Immunohistochemically, this lesion was positive for pancytokeratin, high-molecular-weight keratin, cytokeratin (CK) 7/8, CK19, E-cadherin and p53, but negative for vimentin, CK20, and S-100 protein. The Ki-67 labeling index was 50.3% in the ASCC part and 34.5% in the carcinoma in situ part. These findings and a review of the literature indicate that a gland-like feature of ASCC is associated with the loss of cell adhesion in the center of the cancer nests, and it can be confirmed simply by mucin staining to be neither an adenosquamous carcinoma nor ductal involvement of conventional squamous cell carcinoma.     

Tumour-associated tissue eosinophilia as a prognostic factor in oral squamous cell carcinomas

AIMS: Tumour-associated tissue eosinophilia has been described in many sites, including head and neck. The mechanism of eosinophil recruitment and its role in tumours has not yet been defined, and its presence has been related to a favourable as well as unfavourable prognosis. The aim of this study was to evaluate the influence of tumour-associated tissue eosinophilia on the prognosis of 125 oral squamous cell carcinoma patients. METHODS AND RESULTS: The number of eosinophils was obtained by morphometric analysis and ranged from 0 to 392 per mm2. Tumour-associated tissue eosinophilia was classified according to intensity as mild, moderate, or intense and correlated statistically to the intensity of the mononuclear inflammatory infiltrate as well as to the location of the eosinophilic inflammatory infiltrate. The multivariate analysis demonstrated that intense tumour-associated tissue eosinophilia is an independent favourable prognostic factor for oral squamous cell carcinomas. CONCLUSION: These findings suggest an anti-tumoral role of eosinophils not as yet well understood that should be better investigated.