Serum immunoglobulins in squamous cell carcinoma of the oral cavity

Serum immunoglobulins (IgG, IgA, and IgM) have been studied in 70 patients with squamous cell carcinoma of oral cavity and in 40 age-matched normal controls. The results were correlated with clinical stage, tumor size, lymph node status, tumor differentiation, and treatment modalities. There was a significant rise in serum IgM and IgA in oral cancer patients as compared to controls. It was further raised in advanced clinical stage, but tumor size and histological differentiation and treatment modalities (surgery and chemotherapy) do not seem to affect serum immunoglobulin levels. The observations implies that the extension and dissemination of tumor mass is the important factor for the change in serum immunoglobulin level in squamous cell carcinoma of the oral cavity.     

Current treatment options in squamous cell carcinoma of the oral cavity

Oral cavity SCC remains a significant health problem and requires a multidisciplinary approach. Treatment with surgery alone or in combination with adjuvant radiotherapy for more advanced lesions is the standard of care. Major advances have been made in surgical approaches,reconstructive options, and the rehabilitation of patients who have oral cavity SCC. These advances have significantly improved disease-specific outcome and quality of life. The future may lie in the development of treatment regimes that combine early detection with organ preservation and result in improved cure rates and quality of life.     

Cell surface antigens in squamous cell carcinoma of the oral cavity

The ABH isoantigen was investigated in 80 patients with squamous cell carcinoma of the oral cavity and in their 46 affected lymph nodes. Isoantigen deletion shows a characteristic pattern of benign to malignant transformation of oral cancer. Total loss of isoantigen was found in anaplastic tumours, in metastatic lymph nodes and in the majority of advanced stage tumours. Total loss of isoantigen in metastatic lymph nodes indicates a frequent discharge of isoantigen-negative metastatic cells from the primary tumours to the lymph nodes and the regional organs. It seems that with the recent techniques a prospective observation of ABH isoantigen added to other pathological and clinical findings could be of prognostic significance in patients with squamous cell carcinoma of the oral cavity.     

Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma

BACKGROUND: The survival of patients with head and neck squamous cell carcinoma (HNSCC) remains unaffected despite recent therapeutic advances. To reverse this trend, reliable and clinically applicable markers of tumor aggressiveness must be identified. One such marker may be the tumor-associated macrophage content. The authors hypothesized that tumor-associated macrophages contribute to HNSCC aggressiveness, and the objective of the current study was to prove this hypothesis using mRNA expression analysis and a large cohort of clinical specimens. METHODS: Oligonucleotide microarray analysis was performed on a prospective cohort of 20 patients with previously untreated oral cavity or oropharynx squamous cell carcinoma (OC/OP SCCA) and on normal oropharyngeal mucosa from 4 patients. After determining whether macrophage chemoattractants were produced by tumors, conditioned media from three HNSCC cell lines were used to quantify macrophage migration in an in vitro assay. A high-density tissue microarray of 102 patients with previously untreated OC/OP SCCA was stained immunohistochemically for CD68 to identify tissue macrophages, and the results were correlated with clinicopathologic data and survival. RESULTS: Monocyte chemoattractant protein 1 was up-regulated significantly in tumors compared with normal mucosa (P=0.0025; fold change=1.89). All University of Michigan SCC tumor cell line conditioned media caused a significant increase in macrophage migration (P <0.05). Tissue microarray data revealed that macrophage content of the primary tumor was associated strongly with lymph node metastasis (P <0.0001), extracapsular lymph node spread (P=0.0001), and advanced clinical disease stage (P=0.0002). When it was evaluated along with other clinicopathologic data, the macrophage content was found to be an independent predictor of lymph node metastasis (P <0.0001). CONCLUSIONS: Primary tumor macrophage content is a strong predictor of tumor aggressiveness in HNSCC.     

Survivin as prognostic factor in squamous cell carcinoma of the oral cavity

A series of 78 cases of oral squamous cell carcinoma was analysed by immunohistochemistry for expression of survivin, a recent apoptosis inhibitor. All cases were positive for survivin expression and were divided into two groups using a system of scores. Disease-specific survival curves were calculated according to Kaplan-Meier algorithm, and log rank test was used to compare survival curves. Then, Cox regression analysis was applied to determine the single contribution of covariates on survival rate. So, Cox analysis allowed us to detect the variables most associated to survival. Among the studied variables, such as grade of differentiation, tumor size, stage, recurrence of disease, lymph node presence, only stage and recurrence of disease were predictors of outcome; however, when we analyzed the survival without considering recurrence (that was the stronger predictor of death), a stepwise Cox analysis showed that Survivin, stage and grade of differentiation are significantly associated to survival, with a higher value for Survivin. These data suggest that survivin expression may identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype and, therefore, could influence the decision for the therapy at the time of diagnosis.     

Molecular analysis of anoikis resistance in oral cavity squamous cell carcinoma

Oral cavity squamous cell carcinoma (OSCC) is one of the leading causes of cancer deaths worldwide and most of these deaths result from local-regional recurrence and metastases. Evasion of apoptosis is an important hallmark of cancer development and progression, and previous studies have shown that evasion of anoikis, or detachment-induced apoptosis, correlates with a more aggressive phenotype of carcinoma cells in OSCC. To elucidate the cytogenetic and molecular characteristics of anoikis resistance, we generated several cell lines and clones that displayed this cellular phenotype. To test the hypothesis that chromosomal alterations may underlie this phenotypic transformation, we used karyotype analysis to observe changes in the chromosomal structure of anoikis-sensitive and anoikis-resistant cell lines. We further hypothesized that a unique pattern of gene expression was induced by cell-detachment of anoikis-resistant cell lines, and cDNA microarray analysis was performed using a panel of anoikis-resistant oral cancer cell lines grown under attached and detached growth conditions. We identified S100P, KLK6 and CTNNAL1 as genes whose expression levels were differentially regulated in the anoikis-resistant cell lines compared to the anoikis-sensitive cells under detached conditions. These results were verified using real-time RT-PCR. The anoikis-resistant phenotype of squamous cell carcinoma has a distinct genetic expression pattern that is marked by chromosomal alterations that may contribute to differential expression of genes involved in diverse cellular functions. Therapies targeting these potential mediators of anoikis resistance may prove to be beneficial in the treatment of metastatic squamous cell carcinoma.     

Prognostic significance of intratumoral lymphangiogenesis in squamous cell carcinoma of the oral cavity

BACKGROUND: Clinicopathologic data demonstrated that the lymphatic system is the main route for solid tumor metastasis. However, the effect of intratumoral lymphangiogenesis (IL) on prognosis in oral carcinoma is still unknown because, until recently, no reliable markers for lymphatic endothelium were available. The current study analyzed the lymphatic vessels in tumor tissue specimens of patients with primary oral carcinoma using the new marker, PA2.26. METHODS: The authors investigated IL in surgical tissue samples of 61 patients with early-stage (Stages I-II) oral carcinoma. The tissue specimens were stained for PA2.26 and the correlation between IL and relevant parameters was analyzed by the Pearson chi-square test. In a univariate analysis using the Kaplan-Meier method, IL was analyzed against survival and disease-free period. Statistical significance of differences between distributions was studied by the log-rank test. Clinicopathologic parameters, including IL, were entered in a multivariate analysis to determine independent prognostic significance. RESULTS: Thirty-three patients had IL. In the follow-up, a strong association was found between IL and locoregional recurrence (30.3 % of the patients with IL and 7.1% of the patients without IL). The presence of IL did not correlate significantly with the pT classification, primary location, or tumor differentiation. IL was found to have no influence on overall survival in univariate analysis, but there was significant association between IL and disease-free survival (P=0.03). Multivariate analysis revealed IL to be the sole independent factor influencing disease-free interval (P=0.02). CONCLUSIONS: These results suggested that IL is associated with locoregional disease recurrence in early-stage oral carcinoma. The presence of IL was a useful discriminator in predicting the outcome of patients with absence of lymph node metastasis.     

Recurrence and salvage treatment of squamous cell carcinoma of the oral cavity

The aim of this study was to evaluate the incidence and predictive factors for recurrence of oral squamous cell carcinoma (SCC) and outcome according to salvage treatment modality. A retrospective analysis of 127 oral cavity cancer patients who underwent surgery with or without postoperative radiotherapy as initial treatment was performed. Thirty-six patients (28%) were observed with recurrences and/or metastases mostly at the primary site and neck. Seventy-eight percent of recurrences occurred within one year, and 92% within two years after the initial treatment. The rate of recurrence and/or metastases was significantly higher in patients with an advanced pathologic stage, pathologic lymph node and positive resection margin compared to those with an early pathologic stage, negative lymph node and negative resection margin (p<0.05). Especially, regarding the relationship between the rate of locoregional recurrence and local or regional factors, resection margin status was a particularly important, and potentially preventable, independent predictor for locoregional control. Patients who underwent salvage surgery with or without postoperative radiotherapy had significantly improved salvage and total survival times compared with patients who received chemotherapy and/or radiation therapy for their recurrence.     

Cell-mediated immune status in patients with squamous cell carcinoma of the oral cavity

Sixteen untreated patients with squamous cell carcinoma of the oral cavity were tested for in vitro immune status in comparison with the normal healthy donors. The parameters investigated were total leukocyte and lymphocyte counts, percentages and absolute counts of T- and B-cells in circulation, subsets of T-cells identified by the Fc receptors, phytohemagglutinin (PHA), and mixed lymphocyte culture (MLC) responses, natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities, and circulating immune complexes (CICs). Eight of these patients were retested 3 to 6 months after surgery. The results showed that there was an increase in leukocyte and lymphocyte counts, an increase in the percentage and absolute number of B-lymphocytes, an increase in the percentage of T-gamma cells, suboptimal PHA and MLC responses, normal NK and ADCC activities, and increased levels of CICs in untreated oral cancer patients. In the postoperative stage, except for a reduction in leukocyte and lymphocyte counts, other abnormalities remained unchanged. The CICs in treated patients correlated with the tumor load in that in three patients showing recurrence, the CIC level remained elevated, whereas in patients without evidence of the disease the CIC level was either low or comparable to the upper normal limits.     

口腔鳞癌化疗价值的回顾性分析

目的:探讨化疗在口腔鳞癌治疗中的近期疗效和远期影响.方法:对住院治疗的510例口腔鳞癌患者进行回顾性分析.全部患者按治疗分组,观察口腔癌化疗的近期疗效,对比单纯手术组与诱导化疗加手术综合治疗组的生存率、复发率及局部控制率.结果:完成了诱导或单纯化疗的患者185例,近期疗效为67.6%(125/185).29例首诊时因局部晚期I而不能手术的患者经化疗后重新获得手术机会.25例化疗有效的患者缩小了手术切除范围.单纯手术治疗组与诱导化疗加手术综合治疗组预后比较,两组早期病例预后差异无统计学意义,P>0.005;对于晚期病例后者可提高生存率约10%,两组差异无统计学意义,P>0.005.两组的复发率、局部控制率差异无统计学意义,P>0.05.结论:口腔鳞癌化疗近期疗效较好,但诱导化疗不能提高患者总的生存率及局部控制率.     

Outcome analysis of patients with well-differentiated oral cavity squamous cell carcinoma

The prognosis of well-differentiated oral cavity squamous cell carcinoma (OSCC) is better than less-well-differentiated neoplasms. The aim of this retrospective study was to identify prognostic factors in patients with well-differentiated OSCC. The 5-year outcomes of 467 patients with well-differentiated OSCC who underwent radical surgery and neck dissection were analyzed. In the entire cohort, the presence of pathological node metastases (pN+ vs. pN0) was an independent predictor of 5-year outcomes. In pN0 patients, tumor depth (?8 mm) was the only independently prognostic factor for 5-year survival rates on multivariable analysis (disease-free survival [DFS], P = 0.001, hazard ratio [HR] = 2.634, 95% confidence interval [95% CI] = 1.496–4.636; disease-specific survival [DSS], P < 0.001, HR = 6.794, 95% CI = 2.364–19.525). In pN+ patients, level IV/V neck nodal metastases (DFS, P < 0.001, HR = 47.483, 95% CI = 8.942–252.122; DSS, P < 0.001, HR = 14.301, 95% CI = 5.337–38.323), and ?3 positive nodes (DFS, P = 0.037, HR = 2.107, 95% CI = 1.047–4.242; DSS, P = 0.044, HR = 2.093, 95% CI = 1.020–4.295) were independently associated with 5-year outcomes. Our results suggest that a tailored treatment approach in well-differentiated OSCC patients should take into account the presence of either pN0 or pN+ disease.     

Multiple primary cancers in patients with squamous cell carcinoma of the oral cavity

During the 27 years between 1962 and 1988, 984 patients visited the National Cancer Center Hospital for previously untreated squamous cell carcinoma of the oral cavity and lip. The records of all these 984 patients were reviewed to determine the incidence of additional primary carcinoma. 1) One hundred and thirty-five additional carcinomas developed in 111 patients (11.2%) during 5,689.2 person-years of observation. The incidence of additional primary carcinoma was 23.7 per 1,000 person-years. 2) The cumulative rate of additional primary carcinoma during the first five years of observation showed a tendency to increase in the most recently treated patients (from 1980 to 1988). 3) The observed-to-expected ratio (O/E ratio) for all sites was 2.77 and this is significantly high (P less than 0.01). The calculation of the O/E ratio for each site revealed significantly high risks in the oral cavity and pharynx, esophagus and skin. The O/E ratio for the oral cavity and pharynx was extremely high (79.45). 4) The O/E ratio for all sites in each year of follow-up was the highest in the first year, stayed nearly constant from the second to 14th years, and decreased gradually afterwards. Significantly high risk was observed until the 13th year of follow-up. Patients with oral squamous cell carcinoma must be under frequent and regular examination for almost 15 years.     

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

Metastasis via the lymphatics is a major risk factor in squamous cell carcinoma of the oral cavity (OSCC). We sought to determine whether the presence of metastasis in the regional lymph node could be predicted by a gene expression signature of the primary tumor. A total of 18 OSCCs were characterized for gene expression by hybridizing RNA to Affymetrix U133A gene chips. Genes with differential expression were identified using a permutation technique and verified by quantitative RT-PCR and immunohistochemistry. A predictive rule was built using a support vector machine, and the accuracy of the rule was evaluated using crossvalidation on the original data set and prediction of an independent set of four patients. Metastatic primary tumors could be differentiated from nonmetastatic primary tumors by a signature gene set of 116 genes. This signature gene set correctly predicted the four independent patients as well as associating five lymph node metastases from the original patient set with the metastatic primary tumor group. We concluded that lymph node metastasis could be predicted by gene expression profiles of primary oral cavity squamous cell carcinomas. The presence of a gene expression signature for lymph node metastasis indicates that clinical testing to assess risk for lymph node metastasis should be possible.     

Multiple primary cancer risk in patients with squamous cell carcinoma of the oral cavity

During 6375 patient-years of observation, 136 new cancers developed in 117 of 1429 patients with squamous cell carcinoma of the oral cavity. The risk of multiple cancers was excessive in the upper digestive or respiratory tract in patients with squamous cell carcinoma of the oral cavity, accounting for 87 (64%) of the 136 later cancers. In addition, multiplicity of cancers was site-specific, being common in the oral cavity-esophagus-lung axis and uncommon in sites such as the maxillary sinus and epipharynx. In addition, the observed-to-expected ratio was different in each site of the oral cavity-esophagus-lung axis, i.e., 57.5 for the oral cavity and pharynx, 12.0 for the esophagus, 7.3 for the larynx, and 2.0 for lung cancers.     

Primary and recurrent regional metastases for lateralized oral cavity squamous cell carcinoma

ObjectivesMap regional lymph node metastases for lateralized oral cavity squamous cell carcinoma (OCSCC) and evaluate factors associated with regional metastases and recurrence.Materials and methodsRetrospective cohort study of 715 patients with lateralized OCSCC surgically treated in 1997–2011. Analysis was performed using log-rank, Kaplan-Meier, and multivariable logistic and Cox regression.ResultsRegional metastases were identified in ipsilateral levels IIA (24%), IB (18%), III (13%), V (9%), IV (7%), IA (2%) and IIB (1%) and the contralateral neck (3%). Lymphovascular invasion (LVI) (Hazard Ratio [HR] 2.2, 95% Confidence Interval [CI] 1.2–3.9) and T category (T3 vs. T1: HR 4.1, 95% CI 1.9–9.3; T4 vs. T1: HR 2.3, 95% CI 1.2–4.3) were associated with regional metastases. Most (71%) isolated regional metastatic recurrences were in undissected levels of the neck, including 58% in levels IV and V. Tumors of the hard palate (HR 4.3, 95% CI 1.2–16.1), upper alveolus (HR 3.2, 95% CI 1.0–4.7) or with LVI (HR 2.0, 95% CI 1.0–3.9) were associated with isolated regional recurrence. For upper alveolar/hard palate tumors, depth of invasion (DOI) ≥4 mm (P = .003) and LVI (P = .04) were associated with regional metastases.ConclusionsFor lateralized OCSCC, elective neck dissection of level IIB or the contralateral neck may rarely be needed, but additional surgical or radiation treatment of levels IV and V may be considered based on patient risk factors, including T category 3–4 or LVI. For upper alveolar/hard palate tumors, DOI ≥4 mm is an appropriate threshold for elective neck dissection.