Osteopontin expression is an independent factor for poor survival in oral squamous cell carcinoma: a computer‐assisted analysis on TMA sections

Avirović, Manuela; Matušan-Ilijaš, Koviljka; Damante, Giuseppe; Fabrro, Dora; Cerović, Robert; Juretić, Mirna; Grahovac, Blaženka; Jonjić, Nives; Lučin, Ksenija

doi:10.1111/jop.12055

Cited by 10 publications

(8 citation statements)

References 33 publications

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“…In this review we identified several studies that show that increased EMH expression leads to worse LRC and survival. However, in patients that were surgically treated only, EMH expression was also associated with worse outcome . This supports the hypothesis that hypoxia also contributes to a more aggressive tumor phenotype as described above.…”

Section: Discussionsupporting

confidence: 81%

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Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review

et al. 2015

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Awareness increases that the tumor biology influences treatment outcome and prognosis in cancer. Tumor hypoxia is thought to decrease sensitivity to radiotherapy and some forms of chemotherapy. Presence of hypoxia may be assessed by investigating expression of endogenous markers of hypoxia (EMH) using immunohistochemistry (IHC). In this systematic review we investigated the effect of EMH expression on local control and survival according to treatment modality in head and neck cancer (head and neck squamous cell carcinoma [HNSCC]). A search was performed in MEDLINE and EMBASE. Studies were eligible for inclusion that described EMH expression in relation to outcome in HNSCC patients. Quality was assessed using the Quality in Prognosis Studies (QUIPS) tool. Hazard ratios for locoregional control and survival were extracted. Forty studies of adequate quality were included. HIF-1a, HIF-2a, CA-IX, GLUT-1, and OPN were identified as the best described EMHs. With exception of HIF-2a, all EMHs were significantly related to adverse outcome in multiple studies, especially in studies where patients underwent single-modality treatment. Positive expression was often correlated with adverse clinical characteristics, including disease stage and differentiation grade. In summary, EMH expression was common in HNSCC patients and negatively influenced their prognosis. Future studies should investigate the effect of hypoxia-modified treatment schedules in patients with high In summary, EMH expression. These may include ARCON, treatment with nimorazole, or novel targeted therapies directed at hypoxic tissue. Also, the feasibility of surgical removal of the hypoxic tumor volume prior to radiotherapy should be investigated.

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Section: Discussionsupporting

confidence: 81%

“…Thirteen studies studied EMH expression in patients treated with primary surgery only [35][36][37][38][39][40][41][42][43][44][45][46][47]. All studies concerned oral cavity carcinoma (OSCC) and all studies, except two, described that in surgically treated patients, HIF-1a expression significantly decreased the prognosis.…”

Section: Primary Surgerymentioning

confidence: 99%

Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review

et al. 2015

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“…In addition, several lines of evidence suggest that OPN is important for invasion, metastasis, and angiogenesis [28]. Plasma OPN is an independent prognostic marker for OSCC [29][30][31][32]. In particular, OPN was recently proposed as a surrogate marker for hypoxia, the most important predictor for a response to radiation, and thus for radiotherapy outcome in head and neck cancer [30,[33][34][35][36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Osteopontin‐integrin α_vβ₃ axis is crucial for 5‐fluorouracil resistance in oral squamous cell carcinoma

et al. 2014

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“…However, the role of stromal-derived OPN is still not well understood. Avirović et al, studying the relationship between stromal OPN expression and clinicopathological parameters and clinical outcomes, found no significant association [ 23 ]. Tumor OPN plays an important role in tumor development, particularly in tumor invasion and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma

Luo

Chen

Liu

et al. 2015

BioMed Research International

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Background. Osteopontin (OPN) is a multifunctional cytokine involved in cell survival, migration, and adhesion. However, its role in chemosensitivity in locally advanced oral squamous cell carcinoma (OSCC) in humans has not yet been investigated. Methods. We enrolled 121 patients with locally advanced stage IVA/B OSCC receiving cisplatin-based IC followed by CCRT from January 1, 2006, through January 1, 2012. Immunohistochemistry was used to assess OPN expression in OSCC patients' biopsy specimens from paraffin blocks before treatment. In addition, MTT/colony formation assay was used to estimate the influence of OPN in an oral cancer cell line treated with cisplatin. Results. Of the 121 patients, 94 had positive OPN findings and 52 responded to IC followed by CCRT. Positive osteopontin immunostaining also correlated significantly with positive N status/TNM stage/male gender and smoking. Univariate analyses showed that patients whose tumors had a low expression of OPN were more likely to respond to chemotherapy and have a significantly better OS than those whose tumors had a high expression of OPN. Multivariate analysis revealed that prolonged survival was independently predicted for patients with stage IVA disease, negative lymph nodes, and negative expressions of OPN and for those who received chemotherapy with Docetaxel/cisplatin/fluorouracil (TPF). An oral cancer line stimulated with OPN exhibited a dose-dependent resistance to cisplatin treatment. Conversely, endogenous OPN depletion by OPN-mediated shRNA increased sensitivity to cisplatin. Conclusions. A positive expression of OPN predicts a poor response and survival in patients with locally advanced stage IVA/B OSCC treated with cisplatin-based IC followed by CCRT.

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Osteopontin expression is an independent factor for poor survival in oral squamous cell carcinoma: a computer‐assisted analysis on TMA sections

Abstract: OPN is upregulated in tumor and stromal OSCC cells. Tumor cell-derived OPN is involved in tumor progression and can independently predict the clinical outcome. Stromal-derived OPN probably has a different function compared with OPN secreted from tumor cells.

Cited by 10 publications

References 33 publications

Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review

Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review

Osteopontin‐integrin α_vβ₃ axis is crucial for 5‐fluorouracil resistance in oral squamous cell carcinoma

Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma

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Osteopontin expression is an independent factor for poor survival in oral squamous cell carcinoma: a computer‐assisted analysis on TMA sections

Abstract: OPN is upregulated in tumor and stromal OSCC cells. Tumor cell-derived OPN is involved in tumor progression and can independently predict the clinical outcome. Stromal-derived OPN probably has a different function compared with OPN secreted from tumor cells.

Cited by 10 publications

References 33 publications

Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review

Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review

Osteopontin‐integrin αvβ3 axis is crucial for 5‐fluorouracil resistance in oral squamous cell carcinoma

Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma

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Osteopontin‐integrin α_vβ₃ axis is crucial for 5‐fluorouracil resistance in oral squamous cell carcinoma