HIF-1α as a Prognostic in Oral Squamous Cell Carcinoma
HIF-1α as a Prognostic in Oral Squamous Cell Carcinoma
Oral squamous cell carcinoma is the most common cancer in the oral cavity, accounting for 95% of all malignancies. Predicting prognosis and survival of oral cancer patients has been challenging. To date, there are no molecular markers that can be used reliably in routine clinical practice, other than clinical and histological parameters. Numerous molecules have been tested in order to achieve the above objective. Hypoxia-inducible factor (HIF)-1α is a molecule that is mainly activated under hypoxic conditions. According to the article under evaluation, tumors negatively or weakly expressing HIF-1α had a 5-year disease-specific survival of 80% or more, whereas the disease-specific survival in cases with moderate or strong HIF-1α expression was only 49.4 and 33.6%, respectively. The mean disease-specific survival time was 54 months for patients whose tumors showed negative or weak HIF-1α expression, whereas patients with moderate or strong HIF-1α expression survived on average only 38 months (p = 0.001). HIF-1α may have a role to play in diagnostic and clinical practice to predict prognosis of oral cancer, provided the findings are confirmed by more reliable investigations in addition to immunohistochemistry analysis.
This article evaluates an article recently published by Eckert et al. which suggests that hypoxia-inducible factor (HIF)-1α, one of the main markers of hypoxia, can be considered as a prognostic marker in oral squamous cell carcinoma (OSCC). Oral carcinoma accounts for 30% of head and neck carcinoma, which is the fifth most common carcinoma in males and the eighth most common carcinoma in females worldwide. A total of 95% of oral carcinomas are OSCC. Despite recent advances in the treatment of cancers, the 5-year survival rate of OSCC still remains at 50%. Tumor markers in OSCC have been widely evaluated in the hope of improving treatment outcome. One such area that has generated recent interest is tumor-hypoxia markers and their effects on tumor progression.
Hypoxia-inducible factors are heterodimeric transcription factors with α and β subunits. One way in which cells respond to low oxygen levels is via the HIF pathway. HIFs regulate the expression of genes controlling glucose uptake, metabolism, angiogenesis, erythropoiesis, cell proliferation and apoptosis. HIF is mainly activated under hypoxic conditions. It can also be activated by genetic alterations. Under normal oxygen concentrations, hydroxylation leads to the degradation of HIF-1α. At oxygen concentrations between 0.5 and 6%, HIF-1α subunits are stabilized and translocated to the nucleus, leading to the activation of target genes.
It is well established that molecular markers in hypoxia, mainly HIFs, are important in regulating multiple steps in tumorigenesis. Many studies have demonstrated elevated expression of HIF-1α in a variety of human tumors, including bladder, breast, colon, hepatocellular, ovarian, pancreatic, prostate and renal tumors. It has been demonsrated that HIF-1α overexpression correlates with poor patient outcome in head and neck, nasopharyngeal, colorectal, pancreatic, breast, cervical, osteosarcoma, endometrial, ovarian and gastric carcinoma. The role of HIF-1α has been investigated by a few groups in relation to head and neck cancer. However, the results show conflicting findings between the overexpression of HIF-1α and prognosis. Although most studies concluded that overexpression of HIF-1α was associated with poor patient survival, a few studies came to the reverse conclusion. There have been other studies that examined HIF-1α in head and neck squamous cell carcinoma (HNSCC) in patients who received radiotherapy, and reported that its overexpression was significantly related to poor patient outcome.
Despite this recent interest in the field, not many articles have been published to investigate the correlation between HIF-1α and patient outcome in OSCC as a separate entity from HNSCC. Considering the different behaviour of OSCC from HNSCC, it is important that this entity is evaluated separately.
Abstract and Introduction
Abstract
Oral squamous cell carcinoma is the most common cancer in the oral cavity, accounting for 95% of all malignancies. Predicting prognosis and survival of oral cancer patients has been challenging. To date, there are no molecular markers that can be used reliably in routine clinical practice, other than clinical and histological parameters. Numerous molecules have been tested in order to achieve the above objective. Hypoxia-inducible factor (HIF)-1α is a molecule that is mainly activated under hypoxic conditions. According to the article under evaluation, tumors negatively or weakly expressing HIF-1α had a 5-year disease-specific survival of 80% or more, whereas the disease-specific survival in cases with moderate or strong HIF-1α expression was only 49.4 and 33.6%, respectively. The mean disease-specific survival time was 54 months for patients whose tumors showed negative or weak HIF-1α expression, whereas patients with moderate or strong HIF-1α expression survived on average only 38 months (p = 0.001). HIF-1α may have a role to play in diagnostic and clinical practice to predict prognosis of oral cancer, provided the findings are confirmed by more reliable investigations in addition to immunohistochemistry analysis.
Introduction
This article evaluates an article recently published by Eckert et al. which suggests that hypoxia-inducible factor (HIF)-1α, one of the main markers of hypoxia, can be considered as a prognostic marker in oral squamous cell carcinoma (OSCC). Oral carcinoma accounts for 30% of head and neck carcinoma, which is the fifth most common carcinoma in males and the eighth most common carcinoma in females worldwide. A total of 95% of oral carcinomas are OSCC. Despite recent advances in the treatment of cancers, the 5-year survival rate of OSCC still remains at 50%. Tumor markers in OSCC have been widely evaluated in the hope of improving treatment outcome. One such area that has generated recent interest is tumor-hypoxia markers and their effects on tumor progression.
Hypoxia-inducible factors are heterodimeric transcription factors with α and β subunits. One way in which cells respond to low oxygen levels is via the HIF pathway. HIFs regulate the expression of genes controlling glucose uptake, metabolism, angiogenesis, erythropoiesis, cell proliferation and apoptosis. HIF is mainly activated under hypoxic conditions. It can also be activated by genetic alterations. Under normal oxygen concentrations, hydroxylation leads to the degradation of HIF-1α. At oxygen concentrations between 0.5 and 6%, HIF-1α subunits are stabilized and translocated to the nucleus, leading to the activation of target genes.
It is well established that molecular markers in hypoxia, mainly HIFs, are important in regulating multiple steps in tumorigenesis. Many studies have demonstrated elevated expression of HIF-1α in a variety of human tumors, including bladder, breast, colon, hepatocellular, ovarian, pancreatic, prostate and renal tumors. It has been demonsrated that HIF-1α overexpression correlates with poor patient outcome in head and neck, nasopharyngeal, colorectal, pancreatic, breast, cervical, osteosarcoma, endometrial, ovarian and gastric carcinoma. The role of HIF-1α has been investigated by a few groups in relation to head and neck cancer. However, the results show conflicting findings between the overexpression of HIF-1α and prognosis. Although most studies concluded that overexpression of HIF-1α was associated with poor patient survival, a few studies came to the reverse conclusion. There have been other studies that examined HIF-1α in head and neck squamous cell carcinoma (HNSCC) in patients who received radiotherapy, and reported that its overexpression was significantly related to poor patient outcome.
Despite this recent interest in the field, not many articles have been published to investigate the correlation between HIF-1α and patient outcome in OSCC as a separate entity from HNSCC. Considering the different behaviour of OSCC from HNSCC, it is important that this entity is evaluated separately.
