Expression of hypoxia‐inducible factor‐1α is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan

Lin, Pin-Yi; Yu, Chuan‐Hang; Wang, Jeng-Tzung; Chen, Huang-Hsu; Cheng, Shih‐Jung; Kuo, Mark Yen‐Ping; Chiang, Chun-Pin

doi:10.1111/j.1600-0714.2007.00571.x

Cited by 75 publications

(66 citation statements)

References 34 publications

(75 reference statements)

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“…Recent research indicates that the tumor microenvironment such as hypoxia might play an important role in the uptake of FDG (7) involving a variety of mechanisms. Hypoxia is also associated with resistance to chemotherapeutic drugs and poor prognosis (12)(13)(14). Thus, the present study investigated the correlations between the SUVmax of FDG-PET, the histological effect following neoadjuvant chemoradiotherapy, and expression of the hypoxia-related marker HIF-1· which upregulates GLUT-1 and VEGF in OSCC.…”

Section: Discussionmentioning

confidence: 99%

“…It has been noted that the tumor microenvironment of many malignancies contains a hypoxic condition, a condition associated with resistance to anticancer agents and poor prognosis (12)(13)(14). Hypoxia-inducible factor-1· (HIF-1·) was found to be upregulated in a broad range of tumors and is involved in angiogenesis, invasion and altered glucose metabolism (14,15). Therefore, we focused on the hypoxic condition related to malignant potential and glucose metabolism in malignant tumors.…”

Section: Introductionmentioning

confidence: 99%

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SUVmax of FDG-PET correlates with the effects of neoadjuvant chemoradiotherapy for oral squamous cell carcinoma

Miyawaki

Ikeda²,

Hara³

et al. 2010

Oncol Rep

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Abstract. The aim of this study was to analyze the relationship between the maximum standardized uptake value (SUVmax) of 18F-fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) and the effects of neoadjuvant chemoradiotherapy in oral squamous cell carcinoma (OSCC), and to identify the possible biological background of this association. Thirty-seven patients with OSCC, who underwent preoperative FDG-PET followed by cancer treatment with neoadjuvant chemoradiotherapy, were enrolled in this study. The various histological effects following neoadjuvant chemoradiotherapy were compared to the SUVmax in the primary OSCC. These effects were also compared to the immunohistochemical staining score of hypoxia-inducible factor-1· (HIF-1·), glucose membrane transporter (GLUT)-1 and vascular endothelial growth factor (VEGF) in the biopsy specimen. Furthermore, we analyzed the chemosensitivity of KB-3-1 cells to cisplatin under hypoxic conditions using the MTT assay. A negative correlation was observed between the SUVmax and the histological effects following neoadjuvant chemoradiotherapy (p<0.01). The SUVmax was also correlated with the staining score of HIF-1· (p<0.03), but not with GLUT-1 and VEGF. The mean staining score of HIF-1· in the highly effective group was 2.7±1.1, which was significantly lower than that (3.7±0.9) of the poorly effective group (p<0.05). The cell chemosensitivity assay revealed chemoresistant effects under a hypoxic condition in OSCC. In conclusion, the SUVmax is correlated with the effectiveness of neoadjuvant chemoradiotherapy in OSCC.Our clinical and experimental analyses further suggest a possible association of the upregulation of HIF-1· with chemoradiosensitivity in SCC cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SUVmax of FDG-PET correlates with the effects of neoadjuvant chemoradiotherapy for oral squamous cell carcinoma

Miyawaki

Ikeda²,

Hara³

et al. 2010

Oncol Rep

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“…However, clinicopathological variables and tumour-specific molecular markers that can identify patients with the highest risk of local recurrence have yet to be defined. 16,[18][19][20][21][22][23][42][43][44][45][46][47][48][49] Vimentin, a mesenchymal cell marker, associates with components of the cytoskeleton and membrane adhesions. Studies of human epithelial carcinomas, such as breast cancer, hepatocellular carcinoma, colon carcinoma, and prostatic adenocarcinoma, have shown that vimentin expression can be correlated with tumour invasion and a poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of vimentin and aberrant expression of E-cadherin/β-catenin complex in oral squamous cell carcinomas: correlation with the clinicopathological features and patient outcome

et al. 2010

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Oral squamous cell carcinoma is a challenging oncology problem. A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined. Using quantitative immunohistochemistry, we examined the expression of vimentin, E-cadherin, and b-catenin in 83 oral squamous cell carcinoma patients, and the relationships between the expression of these markers and specific clinicopathological features were analysed. The high expression of vimentin was observed in 23 of 43 (53%) tumours from patients who eventually developed a recurrent tumour and was associated with recurrence and death (Po0.001 and o0.001, respectively). The decreased expression of E-cadherin was observed in 36 of 43 (84%) tumours from patients who eventually developed a recurrent tumour and was also associated with recurrence and death (Po0.001 and o0.001, respectively). Although no correlation between b-catenin expression in whole-tumour sections and clinicopathological features was observed, decreased b-catenin expression at the tumour invasive front was closely associated with recurrence and death (P ¼ 0.002 and 0.002, respectively). The expression of vimentin and that of E-cadherin were associated with survival and were independent prognostic factors in univariate and multivariate analyses. Our data show that the overexpression of vimentin was closely associated with recurrence and death in oral squamous cell carcinoma patients. The combination of the upregulation of vimentin and aberrant expression of E-cadherin/b-catenin complexes at the tumour invasive front may provide a useful prognostic marker in oral squamous cell carcinoma. Modern Pathology (2010) 23, 213-224; doi:10.1038/modpathol.2009 published online 13 November 2009 Keywords: vimentin; oral squamous cell carcinoma; immunohistochemistry Oral cancer is the sixth most frequently occurring cancer worldwide, accounting for 3-5% of all malignancies in both sexes.1,2 Over 90% of all oral carcinomas are classified as oral squamous cell carcinoma, which remains a challenging oncology problem.3 Although early-stage oral squamous cell carcinoma can be treated or cured, the prognosis for advanced oral squamous cell carcinoma (stage III and IV) is poor. The treatment of oral squamous cell carcinoma is usually based on surgery or radiation, with or without concomitant chemotherapy. Despite these advanced therapeutic strategies, the 5-year survival rate of oral squamous cell carcinoma (B50%) has not increased over the past four decades.3-5 Local or regional relapse and cervical lymph node metastasis are the most prevalent

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“…HIF-1 is recognized as a key player in the transcriptional response to hypoxia (11)(12)(13). HIF-1 is a heterodimer composed of an a-subunit (HIF-1a) and a b-subunit (HIF-1b), and its activity is mainly dependent on the stability and modification of HIF-1a, the expression of which is highly regulated (10,12).…”

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confidence: 99%

¹⁸F-Fluoromisonidazole PET Uptake Is Correlated with Hypoxia-Inducible Factor-1α Expression in Oral Squamous Cell Carcinoma

et al. 2013

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Hypoxia is a common feature of cancer and a prognostic factor for many types of cancer. 18 F-fluoromisonidazole ( 18 F-FMISO) PET can detect tumor hypoxia noninvasively. Hypoxia-inducible factor-1 (HIF-1) is a key player in the transcriptional response to low oxygen tension in many types of cancer. Its activity is mainly dependent on the stability and modification of HIF-1a, which is a composition of HIF-1. However, it is unclear whether 18 F-FMISO PET can identify HIF-1a expression in oral squamous cell carcinoma (OSCC). The present study was performed to elucidate the correlation between 18 F-FMISO PET findings and HIF-1a expression in OSCC. Methods: Twenty-three patients (age range, 42-84 y; 15 men, 8 women) with OSCC were enrolled in this study. The T-stages of cancer were T1 in 1 patient, T2 in 9, T3 in 2, and T4a in 11. The N-stages were N0 in 13 patients, N1 in 5, and N2 in 5. Each patient underwent 18 F-FMISO and 18 F-FDG PET before surgery, and the maximum standardized uptake value (SUV max ) of both PET studies was measured. HIF-1a expression in the operation materials was evaluated by immunohistochemical staining. The SUV max of both PET studies and HIF-1a findings were compared statistically. Results: 18 F-FMISO PET detected uptake in the primary site in 14 of the 23 patients (61%). The median SUV max of 18 F-FMISO and 18 F-FDG PET in the primary site was 1.83 (range, 0.8-2.7) and 16.5 (range, 1.0-32.3), respectively. There was a weak significant correlation between 18 F-FMISO and 18 F-FDG PET SUV max (P 5 0.02, r 5 0.48). HIF-1a expression was clearly detected in 11 of the 23 patients (48%). The 18 F-FMISO PET SUV max was significantly higher in the HIF-1a-positive cases than in the HIF-1a-negative cases (median, 2.1; range, 1.5-2.4, vs. median, 1.6; range, 0.8-2.0, respectively) (P 5 0.002). However, there were no significant correlations between 18 F-FDG PET SUV max and HIF-1a expression (median, 21.8; range, 7.7-29.1 vs. 1.0-32.2) (P 5 0.06). Conclusion: 18 F-FMISO uptake in the primary site of OSCC indicates a hypoxic environment with HIF-1a expression.

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Expression of hypoxia‐inducible factor‐1α is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan

Abstract: We conclude that the expression of HIF-1 alpha is an early event in oral carcinogenesis. The nuclear HIF-1 alpha LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.

Cited by 75 publications

References 34 publications

SUVmax of FDG-PET correlates with the effects of neoadjuvant chemoradiotherapy for oral squamous cell carcinoma

SUVmax of FDG-PET correlates with the effects of neoadjuvant chemoradiotherapy for oral squamous cell carcinoma

Upregulation of vimentin and aberrant expression of E-cadherin/β-catenin complex in oral squamous cell carcinomas: correlation with the clinicopathological features and patient outcome

¹⁸F-Fluoromisonidazole PET Uptake Is Correlated with Hypoxia-Inducible Factor-1α Expression in Oral Squamous Cell Carcinoma

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Expression of hypoxia‐inducible factor‐1α is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan

Abstract: We conclude that the expression of HIF-1 alpha is an early event in oral carcinogenesis. The nuclear HIF-1 alpha LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.

Cited by 75 publications

References 34 publications

SUVmax of FDG-PET correlates with the effects of neoadjuvant chemoradiotherapy for oral squamous cell carcinoma

SUVmax of FDG-PET correlates with the effects of neoadjuvant chemoradiotherapy for oral squamous cell carcinoma

Upregulation of vimentin and aberrant expression of E-cadherin/β-catenin complex in oral squamous cell carcinomas: correlation with the clinicopathological features and patient outcome

18F-Fluoromisonidazole PET Uptake Is Correlated with Hypoxia-Inducible Factor-1α Expression in Oral Squamous Cell Carcinoma

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¹⁸F-Fluoromisonidazole PET Uptake Is Correlated with Hypoxia-Inducible Factor-1α Expression in Oral Squamous Cell Carcinoma