An Immunohistochemical Study of HIF-1 Alpha in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

Patel, Nikita Rajendrakumar; Jain, Leena; Mahajan, Aarti; Hiray, Poonam Vilas; Shinde, Sandeep S; Patel, Pranjal

doi:10.1007/s12070-019-01597-y

Cited by 14 publications

(15 citation statements)

References 18 publications

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“…On the other hand, our findings regarding the presentation of HIF‐1α were inconsistent with previous reports that found a gradual and statistical increase in the expression of HIF‐1α from normal mucosa through different grades of OED to OSCC 24 . However, this can be attributed to the fact that these studies reported HIF‐1α expression quantitatively based on the percentage of positive cells rather than qualitatively.…”

Section: Discussioncontrasting

confidence: 99%

Automated immunohistochemical quantification of hypoxia biomarkers shows correlation with dysplastic epithelial changes

Kujan

Siddiqui

Lee

et al. 2023

J Oral Pathology Medicine

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Background: Dysregulation of the hypoxia-aerobic system has been postulated in various malignancies. Nonetheless, the contribution of hypoxia to oral carcinogenesis is yet to be elucidated. Understanding this mechanism is important for improving diagnostic tools and targeted therapies. This study aimed to assess the dysregulation of hypoxia-related factors during different stages of oral squamous cell carcinoma (OSCC) development.Methods: Ninety-two patients diagnosed clinically with oral leukoplakia or OSCC were included and classified according to their histopathological diagnoses. A panel of seven hypoxia-related antibodies were used for immunohistochemical staining of each case. Automated quantification of immunostaining was used for objective reporting. Microvessel density was also assessed.Results: Significant associations were reported for non-dysplastic epithelial changes and malignancy for Glut1, HIF-1α, vascular endothelial growth factor, and signal transducer and activator of transcription 3(p < 0.005). Similarly, microvessel density significantly increased with the severity of epithelial disorders. A multiple regression model including the H-score of HIF-1α and microvessel density could statistically significantly predict the grade of epithelial disorder (p < 0.005). The associated diagnostic accuracy of this approach was 88%.Conclusions: Hypoxia-associated events are observed during early epithelial dysplastic changes and have a potential role in oral carcinogenesis. The level of hypoxia may assist in stratifying the severity of epithelial changes among patients with oral leukoplakia.

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Section: Discussioncontrasting

confidence: 99%

Automated immunohistochemical quantification of hypoxia biomarkers shows correlation with dysplastic epithelial changes

Kujan

Siddiqui

Lee

et al. 2023

J Oral Pathology Medicine

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“…The HIF-1α expression pattern could be used to discriminate healthy mucosa, precursor lesions and OSCC. Furthermore, epithelial dysplastic lesions with an increased HIF-1α expression had a greater risk of malignant transformation, suggesting that the expression of HIF-1α is an early event in oral carcinogenesis [ 75 ]. Moreover, HIF-1α could be employed to characterize aggressive subtypes in early OSCC stages.…”

Section: Translational Aspects Of Hif-1α In Oral Cancer Developmenmentioning

confidence: 99%

Current Understanding of the HIF-1-Dependent Metabolism in Oral Squamous Cell Carcinoma

Eckert

Kappler

Große

et al. 2020

IJMS

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Oral squamous cell carcinoma (OSCC) is the 10th most frequent human malignancy and is thus a global burden. Despite some progress in diagnosis and therapy, patients’ overall survival rate, between 40 and 55%, has stagnated over the last four decades. Since the tumor node metastasis (TNM) system is not precise enough to predict the disease outcome, additive factors for diagnosis, prognosis, prediction and therapy resistance are urgently needed for OSCC. One promising candidate is the hypoxia inducible factor-1 (HIF-1), which functions as an early regulator of tumor aggressiveness and is a key promoter of energy adaptation. Other parameters comprise the composition of the tumor microenvironment, which determines the availability of nutrients and oxygen. In our opinion, these general processes are linked in the pathogenesis of OSCC. Based on this assumption, the review will summarize the major features of the HIF system-induced activities, its target proteins and related pathways of nutrient utilization and metabolism that are essential for the initiation, progression and therapeutic stratification of OSCC.

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“…15,16 Study on oral carcinomas showed that the expression of HIF-1α is an early event in carcinogenesis. 17 The explanation behind this theory is that HIF-1α expression reflects the level of oxygen reduction in tumor tissue, which is a characteristic of fast-growing tumors, particularly early forms of carcinomas. Kwon et al found various radioresistance among patients with early stages of LSCC, depending on the different levels of HIF-1α expression and tumor hypoxia.…”

Section: Discussionmentioning

confidence: 99%

The Expression of Hypoxia-Related Biomarkers: A Significance of HIF-1α C1772T Polymorphism as Predictor of Laryngeal Carcinoma Relapse

et al. 2022

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Introduction The association between the expression of HIF-1α in the laryngeal carcinoma and the prognosis of disease is quite well documented, but the significance of HIF-1α C1772T polymorphism and its relation to disease phenotype have to be clarified. The aim of this study was to investigate the influence of C1772T polymorphism on the clinical-pathological characteristics and disease-free survival after initial surgical treatment of patients with laryngeal carcinoma. Materials and methods The prospective cohort study included 65 patients with laryngeal carcinoma. Two representative tumor tissue specimens were taken in each patient during surgery; 1 specimen was used to asses HIF-1α C1772T polymorphism and the other 1 to determine the immunohistochemical expression of HIF-1α, VEGF, as well as CD 34 proteins. The comparison of polymorphism frequency between study and control population was conducted by collecting a 5 mL of peripheral venous blood samples in each subject. Results Clinicopathological characteristics of laryngeal carcinoma didn’t affect the expression of hypoxia-related biomarkers, such as HIF-1α, VEGF or MVD. The statistically significant association between HIF-1α and VEGF expression was found ( P = .034), but not between HIF-1α expression and MVD value ( P = .696). The expression of HIF-1α was significantly higher among CT heterozygotes ( P = .029). We found a significantly more recurrence among CT heterozygotes compared with patients with CC homozygous alleles (57.10% and 24.30%, respectively; P = .007). Patients with C1772T polymorphic variants had significantly worse disease-free survival compared with patients without polymorphism (Log-rank test, P = .007). Conclusion HIF-1α C1772T polymorphism was significantly associated with worse disease-free survival which nominates it as a predictor of laryngeal carcinoma relapse. The preoperative assessment of hypoxia-related biomarkers should be used in everyday practice in order to determine the treatment modalities for laryngeal carcinoma.

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An Immunohistochemical Study of HIF-1 Alpha in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

Cited by 14 publications

References 18 publications

Automated immunohistochemical quantification of hypoxia biomarkers shows correlation with dysplastic epithelial changes

Automated immunohistochemical quantification of hypoxia biomarkers shows correlation with dysplastic epithelial changes

Current Understanding of the HIF-1-Dependent Metabolism in Oral Squamous Cell Carcinoma

The Expression of Hypoxia-Related Biomarkers: A Significance of HIF-1α C1772T Polymorphism as Predictor of Laryngeal Carcinoma Relapse

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