Abstract
Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. It has been hypothesized that Oct4 positive radioresistant stem cells may be responsible for tumor recurrence. Hence, we evaluated Oct4 expression in ESCC in pre-treatment, post neo-adjuvant residual and post-surgical recurrent tumours. Endoscopic mucosal biopsies were used to study Oct4 expression and the observations were correlated with histological tumor grades, patient data and clinical background. All patients presented with dysphagia with male predominance and a wide age range. Majority of the patients had intake of mixed diet, history of alcohol and tobacco intake was documented in less than half of the patients. Oct 4 expression was significantly higher in poorly differentiated (PDSCC) and basaloid (BSCC) subtypes than the other better differentiated tumor morphology. Oct4 was also expressed by adjoining esophageal mucosa showing low grade dysplasia and basal cell hyperplasia (BCH). Biopsies in PDSCC and BSCC groups were more likely to show a positive band for Oct4 by polymerase chain reaction (PCR). Dysplasia and BCH mucosa also showed Oct4 positivity by PCR. All mucosal biopsies with normal morphology were negative for Oct4. Number of tissue samples showing Oct4 positivity by PCR was higher than that by the conventional immunohistochemistry (p>0.05). Oct4 expression pattern correlated only with tumor grading, not with other parameters including the clinical background or patient data. Our observations highlighted a possible role of Oct4 in identifying putative cancer stem cells in ESCC pathobiology and response to treatment. The implications are either in vivo existence of Oct4 positive putative cancer stem cells in ESCC or acquisition of cancer stem cell properties by tumor cells as a response to treatment given, resulting ultimately an uncontrolled cell proliferation and treatment failure.
Highlights
Esophageal squamous cell carcinoma (ESCC) is the eighth most common cancer worldwide and the fifth most common cancer in developing countries (Parkin el al., 2005)
Role of cancer stem cells (CSC) in tumorigenesis is believed to be generated through uncontrolled self renewal of normal stem cell population or the progenitor cell (Gao et al, 2008; Zhang et al, 2008; Ghisolfi et al, 2012; Wicha, 2014)
We examined the patterns of Oct4 expressions in biopsies taken from human ESCC under different clinical settings and esophageal mucosa taken adjacent to the primary tumor focus by immunohistochemistry and conventional polymerase chain reaction (PCR) techniques
Summary
Esophageal squamous cell carcinoma (ESCC) is the eighth most common cancer worldwide and the fifth most common cancer in developing countries (Parkin el al., 2005). ESCC shows great variation in geographic distributions with a remarkably higher incidence in South East Asian and Latin American countries, and eastern Himalayas (Li el al., 1980; Parkin et al, 2001). These wide geographical variations reflect a strong environmental influence. It has been hypothesized that Oct positive radioresistant stem cells may be responsible for tumor recurrence. Materials and Methods: Endoscopic mucosal biopsies were used to study Oct expression and the observations were correlated with histological tumor grades, patient data and clinical background. Oct was expressed by adjoining esophageal mucosa showing low grade dysplasia and basal cell hyperplasia (BCH). The implications are either in vivo existence of Oct positive putative cancer stem cells in ESCC or acquisition of cancer stem cell properties by tumor cells as a response to treatment given, resulting an uncontrolled cell proliferation and treatment failure
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