Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study.

BACKGROUND: In this study, we evaluated the prognostic value of Immunoscore in patients with stage I−III colon cancer (CC) in the Asian population. These patients were originally included in an international study led by the Society for Immunotherapy of Cancer (SITC) on 2681 patients with AJCC/UICC-TNM stages I−III CC. METHODS: CD3+ and cytotoxic CD8+ T-lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The association of Immunoscore with prognosis was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). RESULTS: Immunoscore stratified Asian patients (n = 423) into different risk categories and was not impacted by age. Recurrence-free rates at 3 years were 78.5%, 85.2%, and 98.3% for a Low, Intermediate, and High Immunoscore, respectively (HR[Low-vs-High] = 7.26 (95% CI 1.75−30.19); p = 0.0064). A High Immunoscore showed a significant association with prolonged TTR, OS, and DFS (p < 0.05). In Cox multivariable analysis stratified by center, Immunoscore association with TTR was independent (HR[Low-vs-Int+High] = 2.22 (95% CI 1.10−4.55) p = 0.0269) of the patient's gender, T-stage, N-stage, sidedness, and MSI status. A significant association of a High Immunoscore with prolonged TTR was also found among MSS (HR[Low-vs-Int+High] = 4.58 (95% CI 2.27−9.23); p ≤ 0.0001), stage II (HR[Low-vs-Int+High] = 2.72 (95% CI 1.35−5.51); p = 0.0052), low-risk stage-II (HR[Low-vs-Int+High] = 2.62 (95% CI 1.21−5.68); p = 0.0146), and high-risk stage II patients (HR[Low-vs-Int+High] = 3.11 (95% CI 1.39−6.91); p = 0.0055). CONCLUSION: A High Immunoscore is significantly associated with the prolonged survival of CC patients within the Asian population.

Clinical significance of inflammatory mediators in the pathogenesis of oral cancer.

Oral cancer has become a grave problem in many parts of the globe with two.thirds of the cases occurring in developing countries. Chronic inflammation plays a prominent role in the development of oral cancer. The rationale for molecular targeted prevention of oral cancer is promising. Therefore, there are continued improvements to our understanding of the molecular connections between inflammation and oral cancer. The inflammatory mediators including nuclear factor kappa B, vascular endothelial growth factor, inflammatory cytokines, prostaglandin pathways, p53, reactive oxygen and nitrogen species, and microRNAs are major key players in the pathogenesis of oral cancer. Currently, visual cytology.based techniques and biopsy are used to detect dysplasia and early stage of oral squamous cell carcinoma. These approaches are limited in their ability to judge the severities of oral lesions and are useful only after the appearance of visual changes. Thus, traditional cytological and biopsy assays combined with testing of inflammatory biomarkers would be beneficial for the efficient early detection of oral dysplastic lesions and early stages of oral squamous cell carcinoma.

Evaluation of plasma non-enzymatic antioxidants in breast cancer etiology.

OBJECTIVE: Oxidative stress has emerged as a major etiological factor for breast cancer. Diet derived antioxidants play an important role against oxidative stress and the aim of the present study was to examine roles of non-enzymatic antioxidants in breast cancer in India. METHODS: Plasma non-enzymatic antioxidants; beta-carotene, vitamin A, vitamin E and vitamin C were analyzed spectrophotometrically from 70 healthy female controls, 30 patients with benign breast diseases (BBD) and 125 untreated breast cancer patients (BCPT). RESULTS: Plasma vitamin C levels were significantly lower in patients with BBD as compared to the controls (p= 0.043). Plasma beta-carotene, vitamin E and vitamin C levels were significantly lower in BCPT as compared to the controls (p= 0.0001, p= 0.040 and p= 0.0001, respectively). Plasma vitamin A levels were significantly higher in patients with BBD and BCPT as compared to the controls (p= 0.0001 and p= 0.0001; respectively) and in BCPT as compared to patients with BBD (p= 0.030). ROC curve analysis revealed that plasma beta-carotene and vitamin A could significantly discriminate between controls and patients with BBD (p= 0.016 and p= 0.000; respectively). Plasma beta-carotene, vitamin A, vitamin E and vitamin C could significantly discriminate between controls and BCPT (p= 0.000, p= 0.000, p= 0.001and p= 0.001, respectively). Plasma vitamin E levels could significantly discriminate between patients with BBD and BCPT (p= 0.055). Odds ratio analysis revealed that, increasing levels of plasma beta-carotene, vitamin E and vitamin C were significantly associated with decreased risk of breast cancer (p= 0.0001, p= 0.003, and p= 0.0001; respectively), whereas, increased risk was linked to plasma vitamin A (p= 0.001). CONCLUSIONS: The trends of the current study provide interesting clues to the etiology of breast cancer and suggest significance of interplay of non-enzymatic antioxidants in breast cancer. Further in-depth study is warranted to elucidate role of these antioxidants as a preventive measure.

Role of nitric oxide and antioxidant enzymes in the pathogenesis of oral cancer.

BACKGROUND: Oral cancer is the leading malignancy in India. Nitric oxide and antioxidant enzymes play an important role in etiology of oral cancer. Therefore, the present study evaluates nitric oxide and antioxidant enzyme levels in healthy individual without tobacco habits (NHT, N=30) and healthy individuals with tobacco habits (WHT, n=90), patients with oral precancers (OPC, n=15) and oral cancer patients (n=126). MATERIALS AND METHODS: Blood samples were collected from the subjects. NO2 + NO3 (nitrite+nitrate), superoxide dismutase (SOD) and catalase levels were estimated using highly specific spectrophotometeric methods. Statistical analysis was done by SPSS statistical software version 10. RESULTS: Mean plasma NO2 + NO3 levels were elevated in patients with OPC and oral cancer patients as compared to the controls. Mean activities of erythrocyte SOD and catalase were higher in WHT than NHT. Erythrocyte SOD and catalase levels were higher in WHT and patients with OPC as compared to NHT. The erythrocyte SOD and catalase activities were lower in oral cancer patients than patients with OPC. The erythrocyte SOD activity was higher in advanced oral cancer than the early disease. Erythrocyte catalase activity was lower in poorly differentiated tumors than well and moderately differentiated tumors. Pearson's correlation analysis revealed that alterations in plasma NO2 + NO3 levels were negatively associated with changes in erythrocyte SOD activities. CONCLUSION: The data revealed that the alterations in antioxidant activities were associated with production of nitric oxide in oral cancer, which may have significant role in oral carcinogenesis.