Can Immunoexpression of Cancer Stem Cell Markers Prognosticate Tongue Squamous Cell Carcinoma? A Systematic Review and Meta-Analysis (original) (raw)
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An immunohistochemical score to predict the outcome for oral squamous cell carcinoma
Journal of Oral Pathology & Medicine, 2018
Background: Oral cancer is a major public health problem worldwide, with a poor survival. Our aim was to evaluate several protein markers in oral squamous cell carcinomas (OSCC) and analyse their prognostic value on patient´s survival. Methods: We analysed the expression of EGFR, p53, p27, p16, cyclin D1, cyclin A2, COX-2, Ki-67, Bcl-2, VEGFR-1, and VEGFR-2, by immunohistochemistry on 67 primary OSCC. Cancer-specific survival (CSS) analysis was evaluated by the Cox regression model. Results: Markers showed variable expression between 27.9% to 95.2%. In univariate analysis for CSS we found that four of the tested markers namely, high expression of p53 (P=0.001), EGFR (P=0.003), cyclin A2 (P=0.005) and low expression of p16 (P=0.019), along with clinical stage (P<0.001), tumour size (P<0.001), presence of nodal metastasis (P<0.001), and perineural permeation (P=0.039) were related with decreased survival. Based on these results, we constructed an immunohistochemical score hinging on the possibility that any tumour could express none of these four markers (score 0), one or two markers (score 1), and three or more markers (score 2). In multivariable analysis, this immunohistochemical score revealed an independent prognostic value on cancer-specific survival (P=0.001; HR: 3.7: 95%CI 1.7-7.9). Moreover, we confirmed that in early stage tumours (stage I or II) this score maintained its independent prognostic value (P=0.025; HR: 7.9, 95%CI 1.3-49.1) on CSS. Conclusion: The expression of the markers p53, p16, EGFR and cyclin A in OSCC, combined to give an immunohistochemical score, may identify high-risk subgroups for decreased survival and to further guide therapeutic decisions.
International journal of scientific research, 2018
Background & Objectives: In OSCC, the presence of regional lymph node metastasis at presentation is the most significant adverse prognostic factor and a major determinant of poor survival. Tumor-infiltrating lymphocytes (TILs) often infiltrate solid malignant tumours and extensive lymphocyte infiltration has been related with a more favourable prognosis in patients with various cancers. OSCC often contain large mononuclear cell infiltrates, comprised mainly of T cells, which could reflect an in situ immune reaction against the malignant OSCC cells. The aim of this retrospective study was to evaluate the expression of Cytotoxic T lymphocyte in OSCC using immunohistochemical marker CD8+(CTLs) and correlate these findings with the status of lymphnode. Methods: The study was conducted on tissue sections obtained from histopathologically diagnosed cases of OSCC (n=30) retrieved from the archives of Department of Oral and Maxillofacial Pathology. The sample consisted of cases showing lymph node metastasis (n=15) and those without pathologic lymph node involvement (n=15). The sections were evaluated by using immunohistochemical staining technique with marker CD8 for Cytotoxic T lymphocytes. The mean immunoexpression of Cytotoxic T lymphocyte was evaluated and correlated with lymphnode status. Results: A statistically significant increase in the count of CTLs (CD8+) was observed in lymph node negative pN(-) as compared to lymph node positive cases pN(+) of OSCC. Interpretation & Conclusion: CTLs (CD8+) are involved in modulating the immune response and can contribute to the dissemination or control of metastatic neoplastic cells. It can be considered that T-cell mediated adaptive immunity plays a key role in anti-tumour immunity.
Serum Prognostic Markers in Head and Neck Cancer
Clinical Cancer Research, 2010
Purpose: Recognized prognostic factors do not adequately predict outcomes of head and neck cancer (HNC) patients after their initial treatment. We identified from the literature nine potential serum prognostic markers and assessed whether they improve outcome prediction.
Prognostic significance of lymph node density in squamous cell carcinoma of the tongue
Head & Neck, 2015
Background. Lymph node density (LND) is more useful than the TNM classification in predicting survival after surgery for many cancers. The purpose of this study was to clarify independent prognostic factors for hypopharyngeal squamous cell carcinoma (HPSCC) and broaden the staging system to improve its predictive value. Methods. The present study included 105 patients with HPSCC treated with hypophagectomy and neck dissection between 1993 and 2014. Results. The median LND in patients with HPSCC was 0.060 (range 0.026-0.620). We found a significant difference in LND values between patients with and without recurrence (0.063 vs. 0.030, respectively; p = 0.001). The cutoff value of LND for recurrence was 0.055, with a sensitivity of 68% and specificity of 71%. Cervical lymph node metastasis, advanced pathologic T stage, lymphovascular invasion, LND C0.055, and extracapsular spread had significant adverse effects on 5-year overall and disease-specific survival in a univariate analysis. Multivariate analysis confirmed a significant association between 5-year overall survival and LND C0.055 [hazard ratio (HR) 2.19; 95% confidence interval (CI) 1.06-4.51; p = 0.035] and extracapsular spread (HR 2.47; 95% CI 1.09-5.61; p = 0.030). Furthermore, LND C0.055 (HR 2.30; 95% CI 1.07-4.93; p = 0.034) and extracapsular spread (HR 2.95; 95% CI 1.20-7.29; p = 0.019) were associated with 5year, disease-specific survival. Conclusions. The median LND cutoff values C0.055 are associated with a greater risk of recurrence and survival in patients with HPSCC.
Preoperative SCC Antigen, CRP Serum Levels, and Lymph Node Density in Oral Squamous Cell Carcinoma
Medicine, 2016
The prognostic significance of squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) levels and lymph node density (LND) has been individually recognized in oral squamous cell carcinoma (OSCC). We investigated the relationship between preoperative serum markers (SCC-Ag and CRP) and postoperative prognostic marker (LND) in this study. We retrospectively analyzed 277 OSCC patients who underwent primary curative resection and neck dissection with/or without adjuvant therapy between March 2008 and November 2013. Serum SCC-Ag and CRP levels were measured preoperatively. Distant metastasis, overall survival (OS), and disease-free survival (DFS) were used to evaluate the prognostic significance of preoperative SCC-Ag and CRP levels in relation to LND. LND (cutoff point ≥0.06) correlated with the pathologic tumor status, pathologic nodal metastasis, degree of differentiation, tumor stage, tumor depth (≥10 mm vs <10 mm), and perineural invasion (all P values were <0.001...
Iranian journal of otorhinolaryngology, 2016
90% of the tumors in the head and neck are squamous-cell carcinomas (HNSCC), which have overall 5- year survival rate between 50% -60%. CD44 has been shown to be associated with the prognosis. Biopsy specimens of 51 patients with oral tongue SCC were evaluated by Immunohistochemistry (IHC) for the CD44 antibody. There was no significant correlation between CD44 and survival (P=0.77), age (P=0.4), CD44 and lymph node metastasis (P=0.87), sex (P=0.947), smoking (P=0.287) and tumor size (P=0.813). However, there was significant correlation between smoking and survival. There are widespread discrepancies among the findings in the literature regarding the prognosis of CD44 expression in OCSCC. Our study shows that the expression of CD44 is not a marker of aggressive behavior in oral tongue SCC. Consequently, CD44 cannot be considered as handy tool to establish the tumor behavior, prognosis and 5- year survival rate of these tumors.
Contemporary Clinical Trials Communications
Background: Lymph node involvement is a fundamental prognostic factor in head and neck squamous cell carcinoma (SCC). Lymph node yield (LNY), which is the number of lymph nodes retrieved after neck dissection, and lymph node ratio (LNR), which is the ratio of positive lymph nodes out of the total removed, are measurable indicators that may have the potential to be used as prognostic factors. The present study is designed to define the exact role of LNY and LNR regarding the overall and specific survival of patients affected by oral cavity and oropharyngeal SCC. It has been registered on clinicaltrials.gov database (NCT03534778). Methods: This is a multicenter study involving tertiary care referral centers in Europe and North America. Patients affected by oral cavity, HPV+ and HPVoropharyngeal SCC undergoing neck dissection will be consecutively enrolled and followed-up for up to 5 years. Patients and disease characteristic will be properly recorded and centrally analyzed. The primary end-point is to define reliable cut off-values for LNY and LNR which may serve as prognosticators of survival. This will be achieved through the use of ROC curves. Secondary outcomes will be the Overall survival (OS), Disease Specific Survival (DSS), and Progression Free Survival Hazard Ratios (HR) at 2-, 3-and 5 years, which will be evaluated through the Kaplan-Meier method and the difference in survival attested by the log-rank test. Univariate and multivariate analysis will be performed to understand the association of various outcomes with LNY and LNR.
Stomatological Disease and Science
The study was to correlate the survival of a group of Sri Lankan betel quid induced oral cancer patients with the expression patterns of five cancer stem cell (CSC) markers namely ALDH1, Sox-2, Bmi-1, C-met, and Oct-4. Methods: Archival tissues of 140 oral squamous cell carcinomas (OSCCs) were stained with CSC markers, ALDH1, Sox-2, Bmi-1, C-met, and Oct-4. Survival analysis was performed with SPSS version 20, using Kaplan-Meier survival curves and significance with chi-square test and Breslow's (generalized Wilcoxon) test. Results: Immunohistochemical investigations revealed 55.7%, 58.6%, 40%, 34.6%, and 31.4% of OSCCs showing ALDH1, Sox-2, Bmi-1, C-met and Oct-4 expression respectively. ALDH1 positivity was significantly associated with nodal metastasis (X 2 = 4.6; P = 0.03). Although it did not reach statistical significance, ALDH1 expression was also correlated with poor survival (P = 0.06). No statistically significant findings could be observed when the expression of other CSC markers were correlated with nodal metastasis and survival (P > 0.05). Conclusion: Out of the five CSC markers investigated, only ALDH1 showed promise as a potential marker to predict nodal metastasis and survival in the present study sample of OSCC patients.
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 2017
c-MYC is a potent oncoprotein with roles in a wide range of cellular processes such as differentiation, apoptosis and growth control. Deregulation of the MYC gene is commonly seen in human tumours resulting in overexpression of the protein. Here we studied expression of c-MYC in correlation to clinical outcome in patients with primary squamous cell carcinoma of the mobile tongue. Immunohistochemistry was used to identify c-MYC in a group of 104 tongue squamous cell carcinomas with an antibody directed against the N-terminal part of the protein. Staining was evaluated by multiplying the percentage of c-MYC expressing cells with staining intensity, giving a quick score (QS) for each tumour. All 104 tumours expressed c-MYC at varying levels. Quantitation according to percent of positive cells and staining intensity revealed that most (15/21; 71%) high expressing tumours were seen in males. Within the group of high c-MYC expressing tumours the majority were alive 2 and 5 years after tre...