A three gene immunohistochemical panel serves as an adjunct to clinical staging of patients with head and neck cancer.

Autor:	Ong CJ; Department of General Surgery, Singapore General Hospital, S169856, Singapore.; Division of Surgical Oncology, National Cancer Centre, S169610, Singapore., Shannon NB; Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, S169857, Singapore., Mueller S; Division of Surgical Oncology, National Cancer Centre, S169610, Singapore.; Singhealth Duke-NUS Head and Neck Centre, Singhealth, S169856, Singapore., Lek SM; Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, S169857, Singapore., Qiu X; Department of General Surgery, Singapore General Hospital, S169856, Singapore., Chong FT; Cancer Therapeutics Research Laboratory, National Cancer Centre, S169610, Singapore., Li K; Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, S169857, Singapore., Koh KKN; Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, S169857, Singapore., Tay GCA; Department of General Surgery, Singapore General Hospital, S169856, Singapore.; Singhealth Duke-NUS Head and Neck Centre, Singhealth, S169856, Singapore., Skanthakumar T; Division of Surgical Oncology, National Cancer Centre, S169610, Singapore., Hwang JSG; Department of Anatomical Pathology, Singapore General Hospital, S169856, Singapore., Hon Lim TK; Department of Anatomical Pathology, Singapore General Hospital, S169856, Singapore., Ang MK; Department of Medical Oncology, National Cancer Centre, S169610, Singapore., Tan DSW; Department of Medical Oncology, National Cancer Centre, S169610, Singapore., Tan NC; Singhealth Duke-NUS Head and Neck Centre, Singhealth, S169856, Singapore., Tan HK; Singhealth Duke-NUS Head and Neck Centre, Singhealth, S169856, Singapore., Soo KC; Singhealth Duke-NUS Head and Neck Centre, Singhealth, S169856, Singapore., Iyer NG; Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, S169857, Singapore.; Cancer Therapeutics Research Laboratory, National Cancer Centre, S169610, Singapore.; Singhealth Duke-NUS Head and Neck Centre, Singhealth, S169856, Singapore.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2017 Jun 19; Vol. 8 (45), pp. 79556-79566. Date of Electronic Publication: 2017 Jun 19 (Print Publication: 2017).
DOI:	10.18632/oncotarget.18568
Abstrakt:	Background: Current management of head and neck squamous cell carcinoma (HNSCC) depends on tumor staging. Despite refinements in clinical staging algorithms, outcomes remain unchanged for the last two decades. In this study, we set out to identify a small, clinically applicable molecular panel to aid prognostication of patients with HNSCC. Materials and Methods: Data from The Cancer Genome Atlas (TCGA) was used to derive copy number aberrations and expression changes to identify putative prognostic genes. To account for cross entity relevance of the biomarkers, HNSCC ( n = 276), breast ( n = 808) and lung cancer ( n = 282) datasets were used to identify robust and reproducible markers with prognostic potential. Validation was performed using immunohistochemistry (IHC) on tissue microarrays of an independent cohort of HNSCC ( n = 333). Findings: Using GISTIC algorithm together with gene expression analysis, we identified six putative prognostic genes in at least two out of three cancers analyzed, of which four were successfully optimized for automated IHC. Of these, three were successfully validated; each molecular target being significantly prognostic on univariate analysis. Patients were differentially segregated into four prognostic groups based on the number of genes dysregulated ( p < 0.001). The IHC panel remained an independent predictor of survival after adjusting for known survival covariates including clinical staging criteria in a multivariate Cox regression model ( p < 0.001). . Interpretation: We have identified and validated a clinically applicable IHC biomarker panel that is independently associated with overall survival. This panel is readily applicable, serving as a useful adjunct to current staging systems and provides novel targets for future therapeutic strategies. Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interests.
Databáze:	MEDLINE
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