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Integrating epidermal growth factor receptor assay with clinical parameters improves risk classification for relapse and survival in head-and-neck squamous cell carcinoma.

ABSTRACT: Epidermal growth factor receptor (EGFR) overexpression has been consistently found to be an independent predictor of local-regional relapse (LRR) after radiotherapy. We assessed the extent by which it can refine risk classification for overall survival (OS) and LRR in patients with head-and-neck squamous cell carcinoma (HNSCC).EGFR expression in locally advanced HNSCC was measured by immunohistochemistry in a series of patients randomized to receive accelerated or conventional radiation regimens in a Phase III trial. Subsequently, data of the two series were pooled (N = 533) for conducting a recursive partitioning analysis that incorporated clinical parameters (e.g., performance status, primary site, T and N categories) and four molecular markers (EGFR, p53, Ki-67, and microvessel density).This study confirmed that patients with higher than median levels of tumor EGFR expression had a lower OS (relative risk [RR]: 1.90, p = 0.0010) and a higher LRR (RR: 1.91, p = 0.0163). Of the four markers analyzed, only EGFR was found to contribute to refining classification of patients into three risk classes with distinct OS and LRR outcomes. The addition of EGFR to three clinical parameters could identify patients having up to a fivefold difference in the risk of LRR.Adding pretreatment EGFR expression data to known robust clinical prognostic variables improved the estimation of the probability for OS and LRR after radiotherapy. Its use for stratifying or selecting patients with defined tumor feature and pattern of relapse for enrollment into clinical trials testing specific therapeutic strategy warrants further investigation.

SUBMITTER: Chung CH

PROVIDER: S-EPMC2992592 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Integrating epidermal growth factor receptor assay with clinical parameters improves risk classification for relapse and survival in head-and-neck squamous cell carcinoma.

Chung Christine H CH Zhang Qiang Q Hammond Elizabeth M EM Trotti Andy M AM Wang Huijun H Spencer Sharon S Zhang Hua-Zhong HZ Cooper Jay J Jordan Richard R Rotman Marvin H MH Ang K Kian KK

International journal of radiation oncology, biology, physics 20100821 2

<h4>Purpose</h4>Epidermal growth factor receptor (EGFR) overexpression has been consistently found to be an independent predictor of local-regional relapse (LRR) after radiotherapy. We assessed the extent by which it can refine risk classification for overall survival (OS) and LRR in patients with head-and-neck squamous cell carcinoma (HNSCC).<h4>Methods and materials</h4>EGFR expression in locally advanced HNSCC was measured by immunohistochemistry in a series of patients randomized to receive ...[more]

PMID: 20732768

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Project description:Introduction: Perineural invasion (PNI), a key pathological feature of head and neck squamous cell carcinoma (HNSCC), predicts poor survival. However, the associated clinical characteristics remain uncertain, and the molecular mechanisms are largely unknown. Materials and methods: HNSCC gene expression and corresponding clinical data were downloaded from The Cancer Genome Atlas (TCGA). Prognostic subgroup analysis was performed, and potential PNI risk factors were assessed with logistic regression. PNI-associated gene coexpression modules were identified with weighted gene coexpression network analysis (WGCNA), and key module gene functions and the roles of non-malignant cells in PNI were evaluated with a single-cell transcriptomic dataset (GSE103322). Results: PNI was significantly inversely associated with overall survival (HR, 2.08; 95% CI, 1.27 to 3.40; P = 0.004), especially in advanced patients (HR, 2.62; 95% CI, 1.48 to 4.64; P < 0.001). Age, gender, smoking history, and alcohol history were not risk factors. HPV-positive cases were less likely than HPV-negative cases to develop PNI (OR, 0.28; 95% CI, 0.09 to 0.76; P = 0.017). WGCNA identified a unique significantly PNI-associated coexpression module containing 357 genes, with 12 hub genes (TIMP2, MIR198, LAMA4, FAM198B, MIR4649, COL5A1, COL1A2, OLFML2B, MMP2, FBN1, ADAM12, and PDGFRB). Single-cell transcriptomic data analysis revealed that the genes in the PNI-associated module correlated with the signatures "EMT," "metastasis," and "invasion." Among non-malignant cells, fibroblasts had relatively high expression of the key genes. Conclusion: At the molecular and omic levels, we verified that PNI in HNSCC is a process of invasion rather than simple diffusion. Fibroblasts probably play an important role in PNI. Novelty & Impact Statements The study is a thorough analysis of PNI in HNSCC from the clinical level to the molecular level and presents the first description of cancer-related PNI from the omics perspective to date as far as we know. We verified that PNI in HNSCC is a process of invasion rather than simple diffusion, at the molecular and omic levels. Fibroblasts were found to probably play an important role in PNI by analyzing single-cell transcriptomic data.

Dataset Information

Integrating epidermal growth factor receptor assay with clinical parameters improves risk classification for relapse and survival in head-and-neck squamous cell carcinoma.

Publications

Integrating epidermal growth factor receptor assay with clinical parameters improves risk classification for relapse and survival in head-and-neck squamous cell carcinoma.

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