Comparing ERCC1 protein expression, mRNA levels, and genotype in squamous cell carcinomas of the head and neck treated with concurrent chemoradiation stratified by HPV status

Hao, Desirée; Lau, Harold; Eliasziw, Misha; Box, Adrian; Diaz, Román; Klimowicz, Alexander C.; Shin, Brian; Lees‐Miller, Susan P.; Magliocco, Anthony M.

doi:10.1002/hed.21817

Cited by 18 publications

(31 citation statements)

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“…ERCC1 expression stratified by human papillomavirus (HPV) status in head and neck cancers. At the end, 17 studies containing 1288 patients were included in metaanalysis [11][12][13][14][15][22][23][24][25][26][27][28][29][30][31][32][33].…”

Section: Eligible Studiesmentioning

confidence: 99%

“…In 4 studies ERCC1 expression was determined by more than one method of detection in the same population of patients [11,[14][15]23]. Three studies employed RT-PCR along with IHC [11,15,23].…”

Section: Eligible Studiesmentioning

confidence: 99%

“…Three studies employed RT-PCR along with IHC [11,15,23]. Among IHC employing studies distinction was made between the most frequently used 8F1 antibody and other IHC methods.…”

Section: Eligible Studiesmentioning

confidence: 99%

“…Among IHC employing studies distinction was made between the most frequently used 8F1 antibody and other IHC methods. In two studies other IHC methods were employed along with 8F1 [14,15] and in two further studies other antibodies were used alone [27,30]. In this meta-analysis different methods of detection of the ERCC1 expression were treated as separate datasets leading thus to the total number of 1427 analyzed tissue samples.…”

Section: Eligible Studiesmentioning

confidence: 99%

“…Besides ERCC1 plays a role in several other DNA repair pathways like homologous recombination [8], interstrand cross-link repair [9] and repair of DNA double-strand breaks (DSB) [10]. A correlation between level of ERCC1 expression and clinical outcomes of HNSCC patients treated with platinum-containing therapy has been investigated in numerous studies but the results were not consistent [11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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The prognostic and predictive value of excision repair cross-complementation group 1 (ERCC1) protein in 1288 patients with head and neck squamous cell carcinoma treated with platinum-based therapy: a meta-analysis

Bišof

Petranović

Rakušić

et al. 2015

Eur Arch Otorhinolaryngol

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Section: Eligible Studiesmentioning

confidence: 99%

Section: Eligible Studiesmentioning

confidence: 99%

“…Three studies employed RT-PCR along with IHC [11,15,23]. Among IHC employing studies distinction was made between the most frequently used 8F1 antibody and other IHC methods.…”

Section: Eligible Studiesmentioning

confidence: 99%

Section: Eligible Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The prognostic and predictive value of excision repair cross-complementation group 1 (ERCC1) protein in 1288 patients with head and neck squamous cell carcinoma treated with platinum-based therapy: a meta-analysis

Bišof

Petranović

Rakušić

et al. 2015

Eur Arch Otorhinolaryngol

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Xenograft assessment of predictive biomarkers for standard head and neck cancer therapies

et al. 2015

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Head and neck squamous cell carcinoma (HNSCC) remains a challenging cancer to treat with overall 5-year survival on the order of 50–60%. Therefore, predictive biomarkers for this disease would be valuable to provide more effective and individualized therapeutic approaches for these patients. While prognostic biomarkers such as p16 expression correlate with outcome; to date, no predictive biomarkers have been clinically validated for HNSCC. We generated xenografts in immunocompromised mice from six established HNSCC cell lines and evaluated response to cisplatin, cetuximab, and radiation. Tissue microarrays were constructed from pre- and posttreatment tumor samples derived from each xenograft experiment. Quantitative immunohistochemistry was performed using a semiautomated imaging and analysis platform to determine the relative expression of five potential predictive biomarkers: epidermal growth factor receptor (EGFR), phospho-EGFR, phospho-Akt, phospho-ERK, and excision repair cross-complementation group 1 (ERCC1). Biomarker levels were compared between xenografts that were sensitive versus resistant to a specific therapy utilizing a two-sample t-test with equal standard deviations. Indeed the xenografts displayed heterogeneous responses to each treatment, and we linked a number of baseline biomarker levels to response. This included low ERCC1 being associated with cisplatin sensitivity, low phospho-Akt correlated with cetuximab sensitivity, and high total EGFR was related to radiation resistance. Overall, we developed a systematic approach to identifying predictive biomarkers and demonstrated several connections between biomarker levels and treatment response. Despite these promising initial results, this work requires additional preclinical validation, likely involving the use of patient-derived xenografts, prior to moving into the clinical realm for confirmation among patients with HNSCC.

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Choline phosphate cytidylyltransferase‐α is a novel antigen detected by the anti‐ERCC1 antibody 8F1 with biomarker value in patients with lung and head and neck squamous cell carcinomas

Vaezi

Bepler

Bhagwat

et al. 2014

Cancer

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BACKGROUND Determination of in situ protein levels of ERCC1 with the antibody (8F1) is prognostic of survival in non-small-cell lung cancer (NSCLC). We previously demonstrated that 8F1 recognizes a second nuclear antigen. We identified this antigen and analyzed its value as a biomarker of clinical outcomes. METHODS The second antigen was identified by mass spectrometry. Protein identity and antibody specificity were confirmed through knockdown and overexpression experiments. Immunohistochemistry (IHC) of 187 early stage NSCLC samples and 60 head and neck squamous cell carcinomas (HNSCC) was used to examine the influence of the second antigen on 8F1 immunoreactivity and association with patient outcomes. RESULTS Cholinephosphate citidylyl transferase–α (CCTα, a.k.a. phosphate citidylyl transferase 1 choline alpha (PCYT1A), a phospholipid synthesis enzyme regulated by RAS, is the second antigen of 8F1. In NSCLC, CCTα contributed (rho = 0.38) to 8F1 immunoreactivity. In squamous cell carcinoma of the lung, CCTα was the dominant determinant of 8F1 immunoreactivity, while its contribution in other subtypes of lung cancer was negligible. High expression of CCTα, but not ERCC1, was prognostic of longer disease-free (log-rank p = 0.002), and overall survival (log-rank p = 0.056). Similarly, in HNSCC, CCTα contributed strongly to 8F1 immunoreactivity (rho = 0.74), and high CCTα expression was prognostic of survival (log-rank p = 0.022 for DFS and p = 0.027 for OS). CONCLUSIONS CCTα is the second antigen detected by 8F1. High CCTα expression is prognostic of survival in NSCLC treated by surgery alone and HNSCC. CCTα is a promising biomarker of patient survival and deserves further study.

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Comparing ERCC1 protein expression, mRNA levels, and genotype in squamous cell carcinomas of the head and neck treated with concurrent chemoradiation stratified by HPV status

Abstract: ERCC1 protein expression using the FL297 antibody warrants further study as a potential prognostic marker in SCCHN.

Cited by 18 publications

References 50 publications

The prognostic and predictive value of excision repair cross-complementation group 1 (ERCC1) protein in 1288 patients with head and neck squamous cell carcinoma treated with platinum-based therapy: a meta-analysis

The prognostic and predictive value of excision repair cross-complementation group 1 (ERCC1) protein in 1288 patients with head and neck squamous cell carcinoma treated with platinum-based therapy: a meta-analysis

Xenograft assessment of predictive biomarkers for standard head and neck cancer therapies

Choline phosphate cytidylyltransferase‐α is a novel antigen detected by the anti‐ERCC1 antibody 8F1 with biomarker value in patients with lung and head and neck squamous cell carcinomas

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