Expression of hypoxia-induced factor-1 alpha in early-stage and in metastatic oral squamous cell carcinoma

Abstract

To investigate hypoxia-induced factor-1 alpha expression in distinct oral squamous cell carcinoma subtypes and topographies and correlate with clinicopathological data. Hypoxia-induced factor-1 alpha expression was assessed by immunohistochemistry in 93 cases of OSCC. Clinical and histopathological data were reviewed from medical records. Hypoxia-induced factor-1 alpha status was distinct according to tumor location, subtype and topography affect. In superficial oral squamous cell carcinomas, most tumor cells overexpressed hypoxia-induced factor-1 alpha, whereas hypoxia-induced factor-1 alpha was restricted to the intratumoral region in conventional squamous cell carcinomas. All basaloid squamous cell carcinomas exhibited downregulation of hypoxia-induced factor-1 alpha. Interestingly, metastatic lymph nodes (91.7%, p = 0.001) and the intratumoral regions of corresponding primary tumors (58.3%, p = 0.142) showed hypoxia-induced factor-1 alpha-positive tumor cells. Overall survival was poor in patients with metastatic lymph nodes. Hypoxia-induced factor-1 alpha has distinct expression patterns in different oral squamous cell carcinoma subtypes and topographies, suggesting that low oxygen tension promotes the growth pattern of superficial and conventional squamous cell carcinoma, but not basaloid squamous cell carcinoma. Indeed, a hypoxic environment may facilitate regional metastasis, making it a useful diagnostic and prognostic marker in primary tumors.

Increased expression of hypoxia-inducible factor-1 alpha and its impact on transcriptional changes and prognosis in malignant tumours of the ocular adnexa

“…Among the ocular malignancies HIF-1α protein expression was most pronounced in SCC, which may be attributed to the rapid and voluminous tumour growth of SCCs in contrast to the rather thin and superficially growing lymphomas and melanomas. Our study reveals that most of the tumour cells in SCC of the ocular adnexa were HIF-1α positive (68%, SD 15%), which is in agreement with other SCC of the body [13,14] indicating a putative role for HIF-1α in the pathogenesis of SCC. However, we did not detect enhanced HIF-1α expression in the centre of the tumour or any obvious reduction in HIF-1α expression in cells close to vessels.…”

Glucose metabolism changes during the development and progression of oral tongue squamous cell carcinomas

“…Similarly, the staining intensities of positive tumors were scored as follows: 1 (no staining or weak staining), 2 (moderate staining), or 3 (high staining). These two scores were averaged, and the expression intensity was calculated by multiplying both scores to yield a final score, as follows: (1–6) low-expression or (7–12) high-expression, as described previously (10,11). Examples of the above evaluation method are shown in Fig.…”

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

“…To determine the role of HIF-1α in OSCC, the expression of HIF-1α was analyzed in large cohorts of OSCC lesions by various groups. Ribeiro and coauthors investigated 93 OSCC samples for HIF-1α expression, demonstrating that metastatic lymph nodes and intra-tumoral regions of corresponding primary tumors (91.7%, p = 0.001) expressed HIF-1α at a high frequency [ 73 ]. Qian and coworkers described a prognostic role of both HIF-1α and HIF-2α isoforms for OSCC development, which was associated with an increased risk of mortality in this kind of cancer [ 74 ].…”