Nodal metastasis and survival in oral cancer: Association with protein expression of SLPI, not with LCN2, TACSTD2, or THBS2

Noorlag, Rob; Groep, Petra van der; Leusink, Frank K.J.; Hooff, Sander R. van; Frank, Michael; Willems, Stefan M.; Es, Robert J.J. van

doi:10.1002/hed.23716

Cited by 32 publications

(28 citation statements)

References 35 publications

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“…Tissue cylinders with a diameter of 0.6 mm were punched out, avoiding areas of necrosis, and arrayed in a recipient paraffin block. The TMAs contained normal tonsillar epithelium as control tissue to ensure similarity of staining quality and intensity between the different blocks …”

Section: Methodsmentioning

confidence: 99%

Cytokeratin 19 expression in early oral squamous cell carcinoma and their metastasis: Inadequate biomarker for one-step nucleic acid amplification implementation in sentinel lymph node biopsy procedure

Noorlag

Bree²,

Willems

2017

Head & Neck

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Section: Methodsmentioning

confidence: 99%

Cytokeratin 19 expression in early oral squamous cell carcinoma and their metastasis: Inadequate biomarker for one-step nucleic acid amplification implementation in sentinel lymph node biopsy procedure

Noorlag

Bree²,

Willems

2017

Head & Neck

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“…Nine patients were excluded because HPV status was unknown and seven were excluded because TMA cores were absent for the tumor, leaving 436 patients for the analysis of FGFR1 protein expression (Table 1). This patient cohort was described previously (22,23).…”

Section: Patient Cohortmentioning

confidence: 99%

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Koole

Brunen

Kempen

et al. 2016

Clinical Cancer Research

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Purpose: FGFR1 is a promising therapeutic target in multiple types of solid tumors, including head and neck squamous cell carcinoma (HNSCC). FGFR inhibitors have shown great therapeutic value in preclinical models. However, resistance remains a major setback. In this study, we have investigated the prognostic value of FGFR1 expression in HNSCC, the therapeutic relevance of targeting FGFR with AZD4547, and potential resistant mechanisms.Experimental Design: IHC and FISH were applied on tissue microarrays to investigate FGFR1 protein expression and FGFR1 gene copy numbers in 452 HNSCCs. The sensitivity of HNSCC cell lines to AZD4547, either as single or combination treatment with the EGFR inhibitor gefitinib, was assessed using long-term colony formation assays, short-term viability assays, and biochemical analysis.Results: FGFR1 protein overexpression occurred in 82% (36/ 44) of human papillomavirus (HPV)-positive HNSCC and 75% (294/392) of HPV-negative HNSCC and relates with poor overall survival and disease-free survival in HPV-negative HNSCC [HR, 3.07; 95% confidence interval (CI), 1.74-6.90; P ¼ 0.001 and HR, 1.53; 95% CI, 1.04-2.39; P ¼ 0.033]. Moreover, the FGFR1 gene was amplified in 3% (3/110) of HPV-negative HNSCC. Treatment of the high FGFR1-expressing cell line CCL30 with AZD4547 reduced cell proliferation and FGFR signaling. Two FGFR-amplified cell lines, SCC147 and BICR16, were resistant to AZD4547 treatment due to EGFR signaling. Combined AZD4547 and gefitinib treatment synergistically inhibited the proliferation of resistant cell lines.Conclusions: Here, we identify high FGFR1 expression as a candidate prognostic biomarker in HPV-negative HNSCC. Furthermore, we provide a rationale for treating FGFR1-expressing HNSCC with the FGFR inhibitor AZD4547 and for combining AZD4547 and gefitinib in FGFR inhibitor-resistant HNSCC patients. Clin Cancer Res; 22(15); 3884-93. Ó2016 AACR.

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“…TMAs were stained for KLK5, KLK7 and SPINK5 according to the manufacturer's protocol and as previously described [25]. In brief, 4-μm-thick paraffin sections were deparaffinised.…”

Section: Methodsmentioning

confidence: 99%

The Co-Expression of Kallikrein 5 and Kallikrein 7 Associates with Poor Survival in Non-HPV Oral Squamous-Cell Carcinoma

Leusink

Diest²,

Frank

et al. 2015

Pathobiology

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Objective: Oral squamous-cell carcinoma (OSCC) still has a poor prognosis. Lymph node metastasis (LNM) is a major determinant of treatment decisions and prognosis. Serine protease inhibitor Kazal-type 5 (SPINK5) is the inhibitor of kallikrein 5 (KLK5) and KLK7. SPINK5, KLK5 and KLK7 are three of the genes of a recently validated LNM-predicting gene expression profile in OSCC. This study evaluates their clinicopathological role and value as biomarkers in OSCC. Methods: Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papillomavirus (HPV) status was determined by an algorithm for HPV-16. Protein expression for KLK5, KLK7 and SPINK5 was semi-quantitatively determined in all 83 tumours by immunohistochemistry. All expression data were correlated with clinicopathological parameters. Results: Concurrent loss of KLK5 and KLK7 correlates with worse disease-specific and overall survival (DSS and OS). Multivariate analysis proved that co-expression is an independent prognostic factor for DSS (p = 0.029) and OS (p = 0.001). Conclusion: This report demonstrates that concurrent loss of KLK5 and KLK7 associates with a poor clinical outcome in OSCC and could therefore serve as prognostic marker in this disease.

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Nodal metastasis and survival in oral cancer: Association with protein expression of SLPI, not with LCN2, TACSTD2, or THBS2

Abstract: Although SLPI expression correlates with lymph node metastases, it has no additional value in determining lymph node metastases in early oral cancer. However, it is an independent predictor for both OS and DSS and therefore a relevant prognostic biomarker in OSCC.

Cited by 32 publications

References 35 publications

Cytokeratin 19 expression in early oral squamous cell carcinoma and their metastasis: Inadequate biomarker for one-step nucleic acid amplification implementation in sentinel lymph node biopsy procedure

Cytokeratin 19 expression in early oral squamous cell carcinoma and their metastasis: Inadequate biomarker for one-step nucleic acid amplification implementation in sentinel lymph node biopsy procedure

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

The Co-Expression of Kallikrein 5 and Kallikrein 7 Associates with Poor Survival in Non-HPV Oral Squamous-Cell Carcinoma

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