Understanding molecular markers in recurrent oral squamous cell carcinoma treated with chemoradiation

Abstract

IntroductionOral cancer accounts for approximately 2.1% of all cancers worldwide. In India, oral squamous cell carcinoma (OSCC) is the most common cancer with half a million new cases diagnosed every year. More than 50% of patients eventually develop local recurrence or metastasis usually within the first 2-years following completion of treatment. It is beneficial to analyze the prognostic significance of Cyclin D1, p53 and EGFR which are critical mediators in the pathogenesis of OSCC. The objective of this study was to assess the association of expression of these markers with recurrence and pattern of recurrence in OSCC patients undergoing chemoradiation.Materials and MethodsA Total 290 OSCC cases of locally advanced stage (III, IV) oral cancer with World Health Organization (W.H.O.) performance status of grade 0/1 in the year 2009–2012 were enrolled in the study. Treatment response was assessed according to W.H.O. criteria. Cyclin D1, EGFR and p53 expression in tumor tissue was estimated by immunohistochemical (IHC) method and quantified as percentage positive nuclei.ResultsDuring the 2-years follow up, 56 (19.3%) patients recurred, out of which, 47 (83.9%) were locoregional and 9 (16.1%) distant sites. On correlating, χ2 test showed significant (P < 0.05 or P < 0.01 or P < 0.001) association of marker expressions (Cyclin D1, EGFR and p53) with recurrence. The strong positive expressions of all three markers showed significant association with early time of recurrence. The multivariate logistic regression analysis showed significant (P < 0.05 or P < 0.01 or P < 0.001) association of recurrence with primary site, differentiation, Cyclin D1 and p53 expressions indicating these as an independent predictors of recurrence in OSCC. The Cyclin D1, EGFR and p53 expressions also showed significant (P < 0.001) poor survivals (OS, DFS and RFS) in patients with positive/strong positive expressions than negative expression suggesting their prognosis in OSCC.ConclusionOur results signifies that tumors over expressing Cyclin D1, EGFR and p53 are resistant to chemoradiation and are associated with increased risk of locoregional recurrence and metastasis in OSCC patients undergoing chemoradiation.

Overexpression of EGFR in Oral Premalignant Lesions and OSCC and Its Impact on Survival and Recurrence

“…The majority of our patients were living (57%) at the end of follow up and recurrence was observed in 65% of the total. Authors also report a 5-year survival rate of 40-50% [48] with 50% of patients developing recurrence within the first two years of treatment [4]. We determined that EGFR significantly and independently affected 5 year survival and recurrence, with EGFR positive patients having markedly lower survival rates and increased chances of recurrence.…”

“…In accordance with our study, Gupta et. al also showed that EGFR overexpression was significantly related to recurrence and added that it also meant an early time to recurrence [4]. Moreover, an improved disease-free interval has been observed with low levels of EGFR accompanied by chemoradiation [33].…”

“…The survival of OSCC patients is bleak with a 5-year survival rate of 40-50% [3] which is in part due to patients presenting with advanced disease at the time of diagnosis and partly due to inadequate treatment and disease management strategies. Moreover, 50% of patients are seen to develop recurrence within the first 2 years of treatment leading to a worse prognosis [4]. It was reported by Camisasca et al that 5 year survival rates for OSCC patient with and without recurrence were 30% and 92% respectively [5].…”

Leptin impairs the therapeutic effect of ionizing radiation in oral squamous cell carcinoma cells

“…The changes in the expression of proteins related to the cell cycle, apoptosis, and angiogenesis were shown to affect radiosensitivity of OSCC and HNSCC patients . For example, overexpression of Cyclin D1, EGFR and p53 was associated with resistance to chemoradiation, the risk of locoregional recurrence and metastasis in OSCC patients …”

Effect of TET1 regulating MGMT on chemotherapy resistance of oral squamous cell carcinoma stem cells

“…OSCC accounts for more than 90% of all oral cancers, in addition to exhibiting particularly high incidence and mortality rates. [20][21][22] Thus, this study aimed to examine the effect of TET1 and MGMT in regards to the chemotherapy sensitivity of OSCC stem cells. Through a series of well conducted and controlled experiments, it was ultimately concluded that low-expressed TET1 in OSCC stem cells could stimulate MGMT promoter methylation, thus strengthening the sensitivity of OSCC stem cells to chemotherapeutic drugs, which would as a result largely enhance treatment methods for patients suffering from OSCC.…”